Aminomacrolides and derivatives having immunosuppressive activity

Claim 2

A compound of formula I: ##STR16## or a pharmaceutically acceptable salt thereof, wherein: R is 1) methyl, 2) ethyl, 3) propyl, or 4) allyl; R 1 and R 2 are, independently, 1) --N 3 ; 2) --NHCN; 3) --NR 5 R 6 , wherein R 5 and R 6 are independently, a) hydrogen, b) C 1 -C 12 alkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are independently selected from the group consisting of: i) hydrogen, ii) --OH, iii) C 1 -C 6 alkoxy, iv) --O--CO--C 1 -C 6 alkyl, v) --NR 9 R 10 , wherein R 9 and R 10 are independently, hydrogen, or C 1 -C 6 alkyl, unsubstituted or substituted with phenyl vi) --CONR 9 R 10 , vii) --CO 2 H, viii) --CO--O--C 1 -C 6 alkyl, ix) --S--C 1 -C 6 alkyl, x) --SO--C 1 -C 6 alkyl, xi) --SO 2 --C 1 -C 6 alkyl, xii) halo, xiii) --C 3 -C 7 -cycloalkyl, xiv) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are independently selected from the group consisting of: A) hydrogen, B) C 1 -C 6 alkyl, C) --OH, D) C 1 -C 6 alkoxy, E) --O--CO--C 1 -C 6 alkyl, F) --NR 9 R 10 , wherein R 9 and R 10 are as defined above, G) --CONR 9 R 10 , H) --CO 2 H, I) --CO--O--C 1 -C 6 alkyl, J) halo, K) --NO 2 , L) --CN, and N) --CF 3 , xv) naphthyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, and xvi) --CF 3 , c) C 3 -C 12 alkenyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above, d) C 3 -C 7 cycloalkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above, e) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, f) naphthyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, g) --SO 2 -phenyl, wherein phenyl is unsubstituted or substituted with with M, W and Y, wherein M, W and Y are as defined above, h) --SO 2 --C 1 -C 6 alkyl, i) or where R 5 and R 6 and the N to which they are attached may form an unsubstituted or substituted 3- to 7-membered heterocyclic ring which may include one or two additional heteroatoms independently selected from the group consisting of O, S, or NR 9 , wherein R 9 is as defined above, and where the substituent(s), attached to the carbon atom(s) in the heterocyclic ring is/are independently selected form the group consisting of: i) hydrogen, ii) --OH, iii) C 1 -C 6 alkoxy, iv) --O--CO--C 1 -C 6 alkyl, v) --NR 9 R 10 , wherein R 9 and R 10 are independently, hydrogen, or C 1 -C 6 alkyl, unsubstituted or substituted with phenyl, vi) --CONR 9 R 10 , vii) --CO 2 H, viii) --CO--O--C 1 -C 6 alkyl, ix) --SH, x) halo, xi) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, xii) naphthyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, and xiii) --CF 3 ; 4) --N(R 5 )CO--O--R 11 , wherein R 5 is as defined above and R 11 is C 1 -C 12 alkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above; 5) --N(R 5 )CO--R 12 , wherein R 5 is as defined above and R 12 is a) hydrogen, b) C 1 -C 12 alkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above, c) C 3 -C 12 cycloalkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above, d) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, e) naphthyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, or f) where R 5 and R 12 and the --NCO-- to which they are attached may form an unsubstituted or substituted 5- to 7-membered heterocyclic ring which may include one or two additional heteroatoms independently selected from the group consisting of O, S, or NR 9 , wherein R 9 is as defined above; 6) --N(R 13 )COCH(R 17 )NR 5 R 6 wherein R 5 and R 6 are as defined above, R 13 is selected from the definitions of R 5 , and R 17 is: a) hydrogen, b) C 1 -C 4 alkyl, unsubstituted or substituted with R 18 , wherein R 18 is selected from the group consisting of: i) --OH, ii) C 1 -C 6 alkoxy, iii) --O--CO--C 1 -C 6 alkyl, iv) --SH, v) --S--C 1 -C 6 alkyl, vi) --NR 9 R 10 , wherein R 9 and R 10 are as defined above, vii) --CO 2 H, viii) --CONH 2 , ix) imidazolyl, x) indolyl, xi) phenyl, and xii) p-hydroxyphenyl, or c) phenyl; 7) --N(R 13 )CO(CH 2 ) m NR 5 R 6 , wherein m is 0 or 2-6, R 5 and R 6 are as defined above, and R 13 is selected from the definitions of R 5 , or where R 13 and R 5 and the --NCO(CH 2 ) m N-- to which they are attached may form an unsubstituted or substituted 5- to 7-membered heterocyclic ring; 8) --N═C(R 13 )--NR 5 R 6 , wherein R 5 and R 6 are as defined above, and R 13 is selected from the definitions of R 5 , and wherein if either R 5 or R 6 are hydrogen, the tautomeric structure --NHC(R 13 )═NR 5or6 is also possible; 9) --N(R 14 ) 3 + A - , wherein R 14 is C 1 -C 6 alkyl, unsubstituted or substituted with phenyl or naphthyl, and wherein A - is a counterion; 10) ##STR17## wherein R 15 and R 16 are independently, a) hydrogen, b) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, c) naphthyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, d) --CN, e) --CF 3 , f) --CO--C 1 -C 6 alkyl, or g) --CO--O--C 1 -C 6 alkyl; 11) hydroxy or C 1 -C 6 alkoxy, with the proviso that R 1 and R 2 are not simultaneously hydroxy, C 1 -C 6 alkoxy, or combinations thereof; or 12) where R 1 and R 2 may both be connected to form a 3- to 7-membered heterocyclic ring of the form: ##STR18## wherein p is zero or one, R 5 is as defined above, and Z is a) --CO--, b) --CS--, c) --CO--C 1 -alkyl, d) --CS--C 1 -alkyl, or e) C 1 -C 2 -alkyl, wherein the alkyl may be unsubstituted or substituted with one or more of the following: i) --OH, ii) C 1 -C 6 alkyl, iii) C 1 -C 6 alkoxy, iv) --O--CO--C 1 -C 6 alkyl, v) --NR 9 R 10 , wherein R 9 and R 10 are as defined above, vi) --CONR 9 R 10 , vii) --CO 2 H, viii) --CO--O--C 1 -C 6 alkyl, ix) --S--C 1 -C 6 alkyl, x) --SO--C 1 -C 6 alkyl, xi) --SO 2 --C 1 -C 6 alkyl, xii) halo, xiii) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, or xiv) naphthyl unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above; R 3 is hydrogen, hydroxy, or C 1 -C 6 alkoxyl; R 4 is hydrogen, or R 3 and R 4 taken together form a double bond; X is 0 or (H,OH); and n is 1 or 2.

Claim 3

A compound according to claim 1 wherein the absolute configuration of formula I is as defined in formula III: ##STR19##

Claim 4

The compound according to claim 1 wherein: R is 1) ethyl, 2) propyl, or 3) allyl; R 1 and R 2 are, independently, 1) --N 3 ; 2) --NR 5 R 6 , wherein R 5 and R 6 are independently, a) hydrogen, b) C 1 -C 12 alkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are independently selected from the group consisting of: i) hydrogen, ii) --OH, iii) C 1 -C 6 alkoxy, iv) --O--CO--C 1 -C 6 alkyl, v) --NR 9 R 10 , wherein R 9 and R 10 are independently, hydrogen, or C 1 -C 6 alkyl, unsubstituted or substituted with phenyl, vi) --CONR 9 R 10 , vii) --CO--O--C 1 -C 6 alkyl, viii) halo, xiv) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are independently selected from the group consisting of: A) hydrogen, B) C 1 -C 6 alkyl, C) --OH, D) C 1 -C 6 alkoxy, E) --O--CO--C 1 -C 6 alkyl, F) --NR 9 R 10 , wherein R 9 and R 10 are as defined above, G) --CONR 9 R 10 , H) --CO 2 H, I) --CO--O--C 1 -C 6 alkyl, J) halo, K) --NO 2 , L) --CN, and N) --CF 3 , xv) naphthyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, and xi) --CF 3 , c) C 3 -C 12 alkenyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above, d) C 3 -C 7 cycloalkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above, e) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, f) naphthyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, g) --SO 2 -phenyl, wherein phenyl is unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, h) --SO 2 --C 1 -C 6 alkyl, 3) --N(R 5 )CO--O--R 11 , wherein R 5 is as defined above and R 11 is C 1 -C 12 alkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above; 4) --N(R 5 )CO--R 12 , wherein R 5 is as defined above and R 12 is a) hydrogen, b) C 1 -C 12 alkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above, c) C 3 -C 12 cycloalkyl, unsubstituted or substituted with R 7 and R 8 , wherein R 7 and R 8 are as defined above, d) phenyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above, or e) naphthyl, unsubstituted or substituted with M, W and Y, wherein M, W and Y are as defined above; 5) --N(R 13 )COCH(R 17 )NR 5 R 6 wherein R 5 and R 6 are as defined above, R 13 is selected from the definitions of R 5 , and R 17 is: a) hydrogen, b) C 1 -C 4 alkyl, unsubstituted or substituted with R 18 , wherein R 18 is selected from the group consisting of: i) --OH, ii) C 1 -C 6 alkoxy, iii) --O--CO--C 1 -C 6 alkyl, iv) --SH, v) --S--C 1 -C 6 alkyl, vi) --NR 9 R 10 , wherein R 9 and R 10 are as defined above, vii) --CO 2 H, viii) --CONH 2 , ix) imidazolyl, x) indolyl, xi) phenyl, and xii) p-hydroxyphenyl, or c) phenyl; 6) --N(R 13 )CO(CH 2 ) m NR 5 R 6 , wherein m is 0 or 2-6, R 5 and R 6 are as defined above, and R 13 is selected from the definitions of R 5 ; 7) --N═C(R 13 )--NR 5 R 6 , wherein R 5 and R 6 are as defined above, and R 13 is selected from the definitions of R 5 , and wherein if either R 5 or R 6 are hydrogen, the tautomeric structure --NHC(R 13 )═NR 5 or 6 is also possible; 8) --N(R 14 ) 3 + A - , wherein R 14 is C 1 -C 6 alkyl, unsubstituted or substituted with phenyl or naphthyl, and wherein A - is a counterion; 9) 1-(1,2,3-triazolyl), substituted with R 15 and R 16 , wherein R 15 and R 16 are a) hydrogen, b) phenyl, or c) --CO--O--C 1 -C 6 alkyl; 10) hydroxy or C 1 -C 6 alkoxy, with the proviso that R 1 and R 2 are not simultaneously hydroxy, C 1 -C 6 alkoxy, or combinations thereof; or 11) where R 1 and R 2 may both be connected to form a 3- to 7-membered heterocyclic ring of the form: ##STR20## wherein p is one, R 5 is as defined above, and Z is a) --CO--, b) --CO--C 1 -alkyl, or c) C 1 -C 2 -alkyl; R 3 is hydrogen or hydroxy; R 4 is hydrogen; X is O or (H,OH); and n is 1 or 2; or a pharmaceutically acceptable salt thereof.

Claim 5

A compound of formula I: ##STR21## wherein: R is ethyl, propyl or allyl; R 1 and R 2 are, independently, N 3 --; H 2 N--; CH 3 NH--; (CH 3 ) 2 N--; PhCH 2 NH--; HOCH(CH 3 )CH 2 NH--; CH 2 ═CHCH 2 NH--; + (CH 3 ) 3 N--; CH 3 CONH--; CH 3 COOCH 2 CONH--; PhNHCONH--; HCONH--; CH 3 CH 2 OCONH--; CH 3 OCONH--; PhCH 2 OCONH--; HN═C(CH 3 )NH--; HN═C(CH 2 Ph)NH--; HN═CHNH--; (N'-t-butoxycarbonyl-D-phenylalanine)amido; (N'-t-butoxycarbonyl-L-phenylalanine)amido; (D-phenylalanine)amido; (L-phenylalanine)amido; cyclopropylcarboxamido; adamantylcarboxamido; 1-(4,5-dicarboethoxy-1,2,3-triazole); or hydroxy or C 1 -C 6 alkoxy, with the proviso that R 1 and R 2 are not simultaneously hydroxy, C 1 -C 6 alkoxy, or combinations thereof; R 3 is hydrogen or hydroxy; R 4 is hydrogen; X is O; and n is 2; or a pharmaceutically acceptable salt thereof.

Claim 6

A compound of formula I: ##STR21## wherein: R is ethyl, propyl or allyl; R 1 and R 2 are, independently, N 3 --; H 2 N--; CH 3 NH--; (CH 3 ) 2 N--; PhCH 2 NH--; HOCH(CH 3 )CH 2 NH--; CH 2 ═CHCH 2 NH--; + (CH 3 ) 3 N--; CH 3 CONH--; CH 3 COOCH 2 CONH--; PhNHCONH--; HCONH--; CH 3 CH 2 OCONH--; CH 3 OCONH--; PhCH 2 OCONH--; HN═C(CH 3 )NH--; HN═C(CH 2 Ph)NH--; HN═CHNH--; (N'-t-butoxycarbonyl-D-phenylalanine)amido; (N'-t-butoxycarbonyl-L-phenylalanine)amido; (D-phenylalanine)amido; (L-phenylalanine)amido; cyclopropylcarboxamido; adamantylcarboxamido; 1-(4,5-dicarboethoxy-1,2,3-triazole); or hydroxy or C 1 -C 6 alkoxy, with the proviso that R 1 and R 2 are not simultaneously hydroxy, C 1 -C 6 alkoxy, or combinations thereof; R 3 is hydrogen or hydroxy; R 4 is hydrogen; X is O; and n is 2; or a pharmaceutically acceptable salt thereof.

Claim 7

A compound which is selected from: 17-ethyl-1,14-dihydroxy-12-[2'-(4"-azido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-acetylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-N-(2-propenyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-methylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-methylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(1'"-adamantanecarboxamido)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-cyclopropanecarboxamido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-formamido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(4'",5'"-dicarboethoxy-1'",2'",3'"-triazole)-3"-methoxycyclohexyl]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-acetylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-aminocyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-hydroxy-3"-aminocyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-benzylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(ethoxycarbonyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(N'-phenylaminocarbonyl)amino-3"-methoxycyclohexyl]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-beta-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-alpha-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-beta-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-alpha-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-methylcarbamate-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzylcarbamate-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-acetamidine-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzamidine-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-formamidine-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-allyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-allyl-1-hydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(L-phenylalanyl)-amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(L-phenylalanyl)amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(D-phenylalanyl)amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(D-phenylalanyl)amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(aminoacetylamino)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(aminoacetylamino)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(2"'-hydroxypropylamino)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(2"'-hydroxypropylamino)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(1-aza-4-oxabicyclo[4.4.0]dec-6-yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(1-aza-4-oxabicyclo[4.4.0]-dec-6-yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-trimethylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone iodide; 17-allyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-isopropoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-allyl-1-hydroxy-12-[2'-(4"-amino-3"-isopropoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-propyl-1-hydroxy-12-[2'-(4"-amino-3"-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-acetylamino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.31.0 4 ,9 ]octacos-18-ene-2,3,20,26-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-[4"-(N'-t-butoxycarbonyl-D-phenylalanine)amido-3"-n-propyloxycyclohexyl]-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetra-methyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-[4"-(N'-t-butoxycarbonyl-L-phenylalanine)amido-3"-n-propyloxycyclohexyl]-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetra-methyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-acetoxyacetylamino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(1"'-adamantanecarboxamido-)3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-cyclopropanecarboxamido-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2-(4"-formamido-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"',5"'-dicarboethoxy-1"',2"',3"'-triazole)-3"-n-propyloxycyclohexyl]-1'-methyl-vinyl}-23,23-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-benzylamino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-trimethylamino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone-Iodide; 17-ethyl-1,2,14-trihydroxy-12-[2'-(4"-acetylamino-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.0 4 ,9 ]octacos-18-ene-3,10,16-trione; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(N'-benzylamino-3"-methoxycyclohexy]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-dihydroxy-12-{2'-[4"-(N'-benzylamino-3"-methoxycyclohexy]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(N'-phenylaminocarbonyl)amino-3"-isopropyloxycyclohexy]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(ethoxycarbonyl)amino-3"-n-propyloxycyclohexyl]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-acetylamino-3"-n-propylcyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-dimethylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-dimethylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-dimethylamino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-dimethylamino-3"-n-propylyoxyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzylamino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzylamino-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethyoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(2-phenyl-2-hydroxyethyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethyoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-morpholino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-morpholino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-n-butyloxycyclo-hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-n-butyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-(3-methylbutyloxy)cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-(3-methylbutyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-(2-methylbutyloxy)cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-(2-methylbutyloxy)cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(N-(2-methyl-3-(4-hydroxyphenyl)propenyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(L-Trp)amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]pctacps-18-ene-2,3,10,16-tetraone; or a pharmaceutically acceptable salt thereof.

Claim 8

A compound which is selected from: 17-ethyl-1,14-dihydroxy-12-[2'-(4"-azido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-acetylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-N-(2-propenyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-methylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-methylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(1'"-adamantanecarboxamido)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-cyclopropanecarboxamido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-formamido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(4'",5'"-dicarboethoxy-1'",2'",3'"-triazole)-3"-methoxycyclohexyl]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-acetylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-aminocyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-hydroxy-3"-aminocyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-benzylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(ethoxycarbonyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(N'-phenylaminocarbonyl)amino-3"-methoxycyclohexyl]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-beta-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-alpha-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-beta-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-alpha-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-methylcarbamate-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzylcarbamate-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-acetamidine-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzamidine-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-formamidine-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-allyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-allyl-1-hydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(L-phenylalanyl)-amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(L-phenylalanyl)amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(D-phenylalanyl)amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(D-phenylalanyl)amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(aminoacetylamino)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(aminoacetylamino)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(2"'-hydroxypropylamino)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(2"'-hydroxypropylamino)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(1-aza-4-oxabicyclo[4.4.0]dec-6-yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(1-aza-4-oxabicyclo[4.4.0]-dec-6-yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-trimethylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone iodide; 17-allyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-isopropoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-allyl-1-hydroxy-12-[2'-(4"-amino-3"-isopropoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-propyl-1-hydroxy-12-[2'-(4"-amino-3"-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-acetylamino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.31.0 4 ,9 ]octacos-18-ene-2,3,20,26-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-[4"-(N'-t-butoxycarbonyl-D-phenylalanine)amido-3"-n-propyloxycyclohexyl]-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetra-methyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-[4"-(N'-t-butoxycarbonyl-L-phenylalanine)amido-3"-n-propyloxycyclohexyl]-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetra-methyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-acetoxyacetylamino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(1"'-adamantanecarboxamido-)3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-cyclopropanecarboxamido-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2-(4"-formamido-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"',5"'-dicarboethoxy-1"',2"',3"'-triazole)-3"-n-propyloxycyclohexyl]-1'-methyl-vinyl}-23,23-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-benzylamino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-trimethylamino-3"-ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone-Iodide; 17-ethyl-1,2,14-trihydroxy-12-[2'-(4"-acetylamino-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.0 4 ,9 ]octacos-18-ene-3,10,16-trione; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(N'-benzylamino-3"-methoxycyclohexy]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-dihydroxy-12-{2'-[4"-(N'-benzylamino-3"-methoxycyclohexy]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(N'-phenylaminocarbonyl)amino-3"-isopropyloxycyclohexy]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-{2'-[4"-(ethoxycarbonyl)amino-3"-n-propyloxycyclohexyl]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-acetylamino-3"-n-propylcyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-dimethylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-dimethylamino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-dimethylamino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-dimethylamino-3"-n-propylyoxyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzylamino-3"-isopropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-benzylamino-3"-n-propyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethyoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(2-phenyl-2-hydroxyethyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethyoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-morpholino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-morpholino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-n-butyloxycyclo-hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-n-butyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-(3-methylbutyloxy)cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-(3-methylbutyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-amino-3"-(2-methylbutyloxy)cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1,14-dihydroxy-12-[2'-(4"-amino-3"-(2-methylbutyloxy)cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(N-(2-methyl-3-(4-hydroxyphenyl)propenyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-ethyl-1-hydroxy-12-[2'-(4"-(L-Trp)amido-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4 ,9 ]pctacps-18-ene-2,3,10,16-tetraone; or a pharmaceutically acceptable salt thereof.

Claim 9

The compound of claim 5 which is: ##STR22## wherein R 1 , R 2 and R 3 are selected from: ______________________________________ R.sup.1 R.sup.2 R.sup.3 ______________________________________ ##STR23## ##STR24## ##STR25## ##STR26## ##STR27## ##STR28## ##STR29## ##STR30## H ##STR31## ##STR32## H ##STR33## ##STR34## H ##STR35## ##STR36## H ##STR37## ##STR38## H ##STR39## ##STR40## ##STR41## ##STR42## ##STR43## ##STR44## ##STR45## ##STR46## ##STR47## ##STR48## ##STR49## H ##STR50## ##STR51## ##STR52## ##STR53## ##STR54## H ##STR55## ##STR56## H ##STR57## ##STR58## H ##STR59## ##STR60## H ##STR61## ##STR62## H. ______________________________________

Claim 10

The compound of claim 5 which is: ##STR63##

Claim 11

The compound of claim 5 which is: ##STR64##

Claim 12

The compound of claim 5 which is: ##STR65##

Claim 13

The compound of claim 5 which is: ##STR66##

Claim 14

The compound of claim 5 which is: ##STR67##

Claim 15

The compound of claim 5 which is: ##STR68##

Claim 16

The compound of claim 5 which is: ##STR69##

Claim 17

The compound of claim 5 which is: ##STR70##

Claim 18

The compound of claim 5 which is: ##STR71##

Claim 19

The compound of claim 5 which is: ##STR72##

Claim 20

The compound of claim 5 which is: ##STR73##

Claim 21

The compound of claim 5 which is: ##STR74##

Claim 22

The compound of claim 5 which is: ##STR75##

Claim 23

A pharmaceutical composition for the treatment of immunoregulatory disorders or diseases comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

Claim 24

A pharmaceutical composition for the treatment of resistance to transplantation comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

Claim 25

A pharmaceutical composition for the topical treatment of inflammatory and hyperproliferative skin diseases and/or cutaneous manifestations of immunologically-mediated illnesses comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

Claim 26

A pharmaceutical composition for the treatment of reversible obstructive airways disease comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

Claim 27

A method for the treatment of immunoregulatory disorders or diseases comprising the administration to a mammalian species in need of such treatment an effective amount of the compound of claim 1.

Claim 28

A method for the treatment of resistance to transplantation comprising the administration to a mammalian species in need of such treatment an effective amount of the compound of claim 1.

Claim 29

A method for the topical treatment of inflammatory and hyperproliferative skin diseases and or cutaneous manifestations of immunologically-mediated illnesses comprising the administration to a mammalian species in need of such treatment an effective amount of the compound of claim 1.

Claim 30

A method for the treatment of reversible obstructive airways disease comprising the administration to a mammalian species in need of such treatment of an effective amount of the compound claim 1.