Macrolide immunomodulators

Claim 1

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR20## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is hydrogen; R 9 is (1) --OS(O) 2 CF 3 , (2) --OS(O) 2 F, (3) --OS(O) 2 R 21a wherein R 21a is C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, (4) --OC(O)R 23 wherein R 23 is C 1 -C 10 -loweralkyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkyl-C 1 -C 10 -alkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic, heterocyclic-C 1 -C 10 -alkyl, alkoxy, --O--C 3 -C 10 -cycloalkyl, --O-aryl, --O-heterocyclic, --O--(N-succinimidyl) or 5-tetrazolyl; (5) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--C 1 -C 10 -loweralkyl, --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is carboxy-C 3 -C 10 -alkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (6) --OR 25 wherein R 25 is as defined above, (7) a protected hydroxy group, (8) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (9) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (10) --O(CH(Si(CH 3 ) 3 ))-(CH 2 ) j C(O)OR 20 wherein j is zero or one and R 20 is independently defined as above, (11) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (12) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (13) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (14) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (15) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (16) --O(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (17) --OS(O) 2 N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (18) --O(CH 2 ) i --NHC(O)R 24 wherein R 24 is defined as above, (19) --OCH(R 24 )--SH wherein R 24 is defined as above, (20) --OCH(R 24 )--S--C 1 -C 10 -loweralkyl wherein R 24 is defined as above, (21) --OCH(R 24 )--S-aryl wherein R 24 is defined as above and (22) --N 3 ; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both C 1 -C 10 -alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR21## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 2

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR20## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is hydrogen; R 9 is (1) --OS(O) 2 CF 3 , (2) --OS(O) 2 F, (3) --OS(O) 2 R 21a wherein R 21a is C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, (4) --OC(O)R 23 wherein R 23 is C 1 -C 10 -loweralkyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkyl-C 1 -C 10 -alkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic, heterocyclic-C 1 -C 10 -alkyl, alkoxy, --O--C 3 -C 10 -cycloalkyl, --O-aryl, --O-heterocyclic, --O--(N-succinimidyl) or 5-tetrazolyl; (5) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--C 1 -C 10 -loweralkyl, --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is carboxy-C 3 -C 10 -alkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (6) --OR 25 wherein R 25 is as defined above, (7) a protected hydroxy group, (8) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (9) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (10) --O(CH(Si(CH 3 ) 3 ))-(CH 2 ) j C(O)OR 20 wherein j is zero or one and R 20 is independently defined as above, (11) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (12) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (13) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (14) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (15) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (16) --O(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (17) --OS(O) 2 N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (18) --O(CH 2 ) i --NHC(O)R 24 wherein R 24 is defined as above, (19) --OCH(R 24 )--SH wherein R 24 is defined as above, (20) --OCH(R 24 )--S--C 1 -C 10 -loweralkyl wherein R 24 is defined as above, (21) --OCH(R 24 )--S-aryl wherein R 24 is defined as above and (22) --N 3 ; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both C 1 -C 10 -alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR21## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 3

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR22## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is hydrogen; R 9 is (1) --SR 24 wherein R 24 is (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--C 1 -C 10 -loweralkyl, --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclic-C 1 -C 10 -alkyl) wherein Q, is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --C(O)--O--(C 1 -C 10 -loweralkyl), (j) --C(O)-aryl, (k) --C(O)-heterocyclic or (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl, (2) --SC(═NH)--NH 2 , (3) --SC(═N--NH 2 )--NH 2 , (4) --Se-phenyl or (5) --Se(O)-phenyl; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both C 1 -C 10 -alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR23## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 4

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR22## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is hydrogen; R 9 is (1) --SR 24 wherein R 24 is (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--C 1 -C 10 -loweralkyl, --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclic-C 1 -C 10 -alkyl) wherein Q, is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --C(O)--O--(C 1 -C 10 -loweralkyl), (j) --C(O)-aryl, (k) --C(O)-heterocyclic or (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl, (2) --SC(═NH)--NH 2 , (3) --SC(═N--NH 2 )--NH 2 , (4) --Se-phenyl or (5) --Se(O)-phenyl; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both C 1 -C 10 -alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR23## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 5

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR24## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is hydrogen; R 9 is (1) --N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--(C 1 -C 10 -loweralkyl), --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclic-C 1 -C 10 -alkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl, (2) --N═C═O, (3) --NHC(O)--R* or (4) --NHS(O) 2 --R* wherein R* is (a) C 1 -C 10 -loweralkyl, (b) C 3 -C 10 -cycloalkyl, (c) aryl, (d) heterocyclic, (e) C 1 -C 10 -loweralkyl substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--(C 1 -C 10 -loweralkyl), --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclic-C 1 -C 10 -alkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (f) --N(R a )(R b ) wherein R a and R b are independently selected from hydrogen, C 1 -C 10 -loweralkyl and --N(R c )(R d ) wherein R c and R d are independently selected from hydrogen and C 1 -C 10 -loweralkyl or (g) --OR* wherein R* is defined as above; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl )thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR25## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 6

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR24## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is hydrogen; R 9 is (1) --N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--(C 1 -C 10 -loweralkyl), --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclic-C 1 -C 10 -alkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl, (2) --N═C═O, (3) --NHC(O)--R* or (4) --NHS(O) 2 --R* wherein R* is (a) C 1 -C 10 -loweralkyl, (b) C 3 -C 10 -cycloalkyl, (c) aryl, (d) heterocyclic, (e) C 1 -C 10 -loweralkyl substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--(C 1 -C 10 -loweralkyl), --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclic-C 1 -C 10 -alkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (f) --N(R a )(R b ) wherein R a and R b are independently selected from hydrogen, C 1 -C 10 -loweralkyl and --N(R c )(R d ) wherein R c and R d are independently selected from hydrogen and C 1 -C 10 -loweralkyl or (g) --OR* wherein R* is defined as above; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl )thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR25## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 7

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR26## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein Z is ##STR27## R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 , R 9 , R 18 and R 19 are independently selected from (1) hydrogen, (2) --OS(O) 2 CF 3 , (3) --OS(O) 2 F, (4) --OS(O) 2 R 21a wherein R 21a is C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, (5) --OC(O)R 23 wherein R 23 is --O-aryl, --O--(N-succinimidyl), --O-benzotriazolyl, --O-2'-pyridyl or 5-tetrazolyl; (6) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--(C 1 -C 10 -loweralkyl), --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclic-C 1 -C 10 -alkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (7) --OR 25 wherein R 25 is as defined above, (8) a protected hydroxy group, (9) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (10) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (11) --O(CH(Si(CH 3 ) 3 ))--(CH 2 ) j C(O)OR 20 wherein j is zero or one and R 20 is independently defined as above, (12) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (13) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (14) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (15) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (16) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (17) --O(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (18) --OS(O) 2 N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (19) --O(CH 2 ) i --NHC(O)R 24 wherein R 24 is defined as above, (20) --OCH(R 24 )--SH wherein R 24 is defined as above, (21) --OCH(R 24 )--S--(C 1 -C 10 -loweralkyl) wherein R 24 is defined as above, (22) --OCH(R 24 )--S-aryl wherein R 24 is defined as above, (23) --N 3 , (24) --N═C═O, (25) --N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (26) --NHC(O)--R 24 wherein R 24 is defined as above, (27) --NHC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (28) --S--R 24 wherein R 24 is defined as above and (29) --S--q--R 24 wherein q is a divalent radical selected from the group consisting of --S--, --C(O)--, --C(O)--O--, --C(O)--NH-- and --C(N(R 27 ))--NHNH-- and R 24 and R 27 are defined as above, with the proviso that one of R 8 and R 9 is hydrogen and the other is not hydrogen and one of R 18 and R 19 is hydrogen and the other is not hydrogen; or R 8 and R 9 taken together are (1) oxo, (2) ═N--O--R 24 wherein R 24 is defined as above or (3) ═N--N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above; or R 18 and R 19 taken together are (1) oxo, (2) ═N--O--R 24 wherein R 24 is independently defined as above or (3) ═N--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently defined as above; or one of R 8 and R 9 taken together with one of R 18 and R 19 form a heterocyclic ring with the others of R 8 , R 9 , R 18 and R 19 being hydrogen or together forming a bond; or R 8 and R 18 are hydrogen and R 8 ' and R 19 form a bond; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 --C 10 -alkoxy, C 2 --C 10 -alkenyl, C 2 --C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR28## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 8

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR26## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein Z is ##STR27## R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 , R 9 , R 18 and R 19 are independently selected from (1) hydrogen, (2) --OS(O) 2 CF 3 , (3) --OS(O) 2 F, (4) --OS(O) 2 R 21a wherein R 21a is C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, (5) --OC(O)R 23 wherein R 23 is --O-aryl, --O--(N-succinimidyl), --O-benzotriazolyl, --O-2'-pyridyl or 5-tetrazolyl; (6) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--(C 1 -C 10 -loweralkyl), --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclic-C 1 -C 10 -alkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (7) --OR 25 wherein R 25 is as defined above, (8) a protected hydroxy group, (9) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (10) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (11) --O(CH(Si(CH 3 ) 3 ))--(CH 2 ) j C(O)OR 20 wherein j is zero or one and R 20 is independently defined as above, (12) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (13) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (14) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (15) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (16) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (17) --O(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (18) --OS(O) 2 N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (19) --O(CH 2 ) i --NHC(O)R 24 wherein R 24 is defined as above, (20) --OCH(R 24 )--SH wherein R 24 is defined as above, (21) --OCH(R 24 )--S--(C 1 -C 10 -loweralkyl) wherein R 24 is defined as above, (22) --OCH(R 24 )--S-aryl wherein R 24 is defined as above, (23) --N 3 , (24) --N═C═O, (25) --N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (26) --NHC(O)--R 24 wherein R 24 is defined as above, (27) --NHC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (28) --S--R 24 wherein R 24 is defined as above and (29) --S--q--R 24 wherein q is a divalent radical selected from the group consisting of --S--, --C(O)--, --C(O)--O--, --C(O)--NH-- and --C(N(R 27 ))--NHNH-- and R 24 and R 27 are defined as above, with the proviso that one of R 8 and R 9 is hydrogen and the other is not hydrogen and one of R 18 and R 19 is hydrogen and the other is not hydrogen; or R 8 and R 9 taken together are (1) oxo, (2) ═N--O--R 24 wherein R 24 is defined as above or (3) ═N--N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above; or R 18 and R 19 taken together are (1) oxo, (2) ═N--O--R 24 wherein R 24 is independently defined as above or (3) ═N--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently defined as above; or one of R 8 and R 9 taken together with one of R 18 and R 19 form a heterocyclic ring with the others of R 8 , R 9 , R 18 and R 19 being hydrogen or together forming a bond; or R 8 and R 18 are hydrogen and R 8 ' and R 19 form a bond; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 --C 10 -alkoxy, C 2 --C 10 -alkenyl, C 2 --C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR28## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 9

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR29## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is (1) --OC(O)N(OR 20 )(R 24 ) or (2) --O--C(O)--NHN(R 24 )(R 25 ) wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl or heterocyclic, each of which is optionally substituted with C 1 -C 10 -loweralkyl, hydroxy, aryl or heterocyclic and R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--C 1 -C 10 -loweralkyl, --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q, is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic or (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both C 1 -C 10 -alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 --C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR30## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 --C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 10

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR29## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is (1) --OC(O)N(OR 20 )(R 24 ) or (2) --O--C(O)--NHN(R 24 )(R 25 ) wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl or heterocyclic, each of which is optionally substituted with C 1 -C 10 -loweralkyl, hydroxy, aryl or heterocyclic and R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--C 1 -C 10 -loweralkyl, --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q, is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic or (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both C 1 -C 10 -alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 --C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR30## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 --C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 11

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR31## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is (1) --OC(O)N(OR 20 )(R 24 ) or (2) --O--C(O)--NHN(R 24 )(R 25 ) wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl or heterocyclic, each of which is optionally substituted with C 1 -C 10 -loweralkyl, hydroxy, aryl or heterocyclic and R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--C 1 -C 10 -loweralkyl, --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic or (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (3) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (4) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (5) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (6) --(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above or (7) --(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both C 1 -C 10 -alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR32## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.

Claim 12

A method of immunomodulatory treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR31## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof wherein R 1 is hydrogen, a hydroxy protecting group, C 1 -C 10 -loweralkyl or phenyl-substituted C 1 -C 10 -loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted C 1 -C 10 -loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic or heterocyclic-C 1 -C 10 -alkyl, each of which is optionally substituted with C 1 -C 10 -loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, aryl, aryl-C 1 -C 10 -alkyl, heterocyclic and heterocyclic-C 1 -C 10 -alkyl; R 8 is (1) --OC(O)N(OR 20 )(R 24 ) or (2) --O--C(O)--NHN(R 24 )(R 25 ) wherein R 20 is hydrogen, C 1 -C 10 -loweralkyl, C 2 -C 10 -alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkenyl, C 3 -C 10 -bicycloalkenyl, aryl or heterocyclic, each of which is optionally substituted with C 1 -C 10 -loweralkyl, hydroxy, aryl or heterocyclic and R 24 and R 25 are independently selected from (a) hydrogen, (b) C 1 -C 10 -loweralkyl, (c) C 2 -C 10 -alkenyl, (d) C 2 -C 10 -alkynyl, (e) C 3 -C 10 -cycloalkyl, (f) substituted C 1 -C 10 -loweralkyl, substituted C 2 -C 10 -alkenyl, substituted C 2 -C 10 -alkynyl or substituted C 3 -C 10 -cycloalkyl wherein the C 1 -C 10 -loweralkyl group, the C 2 -C 10 -alkenyl group, the C 2 -C 10 -alkynyl group or the C 3 -C 10 -cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q--C 1 -C 10 -loweralkyl, --Q-aryl, --Q-(aryl-C 1 -C 10 -alkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, C 1 -C 10 -loweralkyl, aryl or heterocyclic, (v) C 3 -C 10 -cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) R 28 and R 29 are independently selected from hydrogen, C 1 -C 10 -loweralkyl, hydroxy-C 1 -C 10 -alkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is C 1 -C 10 -loweralkyl, aryl or aryl-C 1 -C 10 -alkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--(C 1 -C 10 -loweralkyl), (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic or (l) C 1 -C 10 -loweralkyl substituted by --OC(O)--R f wherein R f is C 3 -C 10 -carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (3) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (4) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (5) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (6) --(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above or (7) --(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyl, C 2 -C 10 -alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both C 1 -C 10 -alkoxy or --SR 28a wherein R 28a is C 1 -C 10 -loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo wherein at each occurrence the term "aryl" is independently selected from phenyl, naphthyl, fluorenyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl which is either unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 10 -loweralkyl, halo, halo-C 1 -C 10 -loweralkyl, halo-C 1 -C 10 -alkoxy, C 2 -C 10 -alkenyloxy, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkoxycarbonyl, C 1 -C 10 -alkoxycarbonylalkenyl, (C 1 -C 10 -alkoxycarbonyl)thio-C 1 -C 10 -alkoxy, thio-C 1 -C 10 -alkoxy, amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, aminocarbonyl, aminocarbonyl-C 1 -C 10 -alkoxy, alkanoylamino, aryl-C 1 -C 10 -alkoxy, aryloxy, mercapto, nitro, carboxaldehyde, carboxy, carboxy-C 2 -C 10 -alkenyl, carboxy-C 1 -C 10 -alkoxy, C 1 -C 10 -alkylsulfonylamino, cyano-C 1 -C 10 -alkoxy, (heterocyclic)-C 1 -C 10 -alkoxy, hydroxy, hydroxy-C 1 -C 10 -alkoxy, phenyl, phenyl-substituted C 2 -C 10 -alkenyl, phenyl-substituted C 2 -C 10 -alkynyl, heterocyclic, --S(O) 2 NH 2 , tetrazolyl-C 1 -C 10 -alkoxy, tetrafluorophenyl and pentafluorophenyl and at each occurrence the term "heterocyclic" is independently selected from indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, dihydrobenzofuryl, benzothienyl, azetidinyl, oxetanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl, benzothienyl, compounds of the formula ##STR32## where X* is --CH 2 -- or --O-- and Y* is --C(O)-- or --C(R") 2 --! v where R" is hydrogen or C 1 -C 4 -alkyl and v is 1, 2 or 3, pyridin-2-on-1-yl, pyridin-4-on-1-yl, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, D-talose, D-ribose, D-arabinose, D-xylose, and D-lyxose wherein said heterocyclics are either unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (═O), amino, C 1 -C 10 -alkylamino, C 1 -C 10 -dialkylamino, C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkoxy, alkoxy-C 1 -C 10 -alkyl, halo-C 1 -C 10 -alkyl, hydroxy, hydroxy-C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, aryl, aryl-C 1 -C 10 -alkyl, --COOH, --SO 3 H, --C(O)NH 2 and C 1 -C 10 -loweralkyl.