N2-Arylsulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof

Claim 1

An N 2 -arylsulfonyl-L-argininamide of the formula (I) having the D-configuration in the carbon atom to which the carboxyl group or the ester thereof is attached: ##STR32## or a pharmaceutically acceptable salt thereof, wherein R is ##STR33## wherein R 1 is C 2 -C 10 carboxyalkyl, C 3 -C 10 alkoxycarbonylalkyl or C 8 -C 15 α-carboxyaralkyl; R 2 is hydrogen, C 1 -C 10 alkyl, C 6 -C 10 aryl, C 7 -C 12 aralkyl or 5-indanyl; and n is an integer of 1, 2 or 3, ##STR34## wherein R 3 is C 2 -C 10 carboxyalkyl, C 3 -C 10 alkoxycarbonylalkyl or C 8 -C 15 α-carboxyaralkyl; R 4 is C 1 -C 10 alkyl, phenyl optionally substituted with at least one C 1 -C 5 alkyl, C 1 -C 5 alkoxy, or mixtures thereof, C 7 -C 12 aralkyl, or ring substituted benzyl wherein said substituent is C 1 -C 5 alkyl or C 1 -C 5 alkoxy; R 5 is hydrogen, C 1 -C 10 alkyl, C 6 -C 10 aryl, C 7 -C 12 aralkyl or 5-indanyl; and n' is an integer of 0, 1 or 2, ##STR35## wherein R 6 is hydrogen, C 1 -C 10 alkyl, C 3 -C 10 alkenyl, C 3 -C 10 alkynyl, C 2 -C 10 alkoxyalkyl, C 2 -C 10 alkylthioalkyl, C 2 -C 10 alkylsulfinylalkyl, C 1 -C 10 hydroxyalkyl, C 3 -C 10 alkylcarbonylalkyl, C 1 -C 10 haloalkyl, C 7 -C 15 aralkyl, C 3 -C 10 cycloalkyl, C 4 -C 10 cycloalkylalkyl, furfuryl, tetrahydrofurfuryl optionally substituted with at least one C 1 -C 5 alkyl, C 1 -C 5 alkoxy or mixtures thereof, 3-furylmethyl, tetrahydro-3-furylmethyl optionally substituted with at least one C 1 -C 5 alkyl, C 1 -C 5 alkoxy or mixtures thereof, tetrahydro-2 (3 or 4)-pyranylmethyl optionally substituted with at least one C 1 -C 5 alkyl, C 1 -C 5 alkoxy or mixtures thereof, 1,4-dioxa-2-cyclohexylmethyl optionally substituted with one or more C 1 -C 5 alkyl, C 1 -C 5 alkoxy or mixtures thereof, 2-thenyl, 3-thenyl, tetrahydro-2-thenyl optionally substituted with at least one C 1 -C 5 alkyl, C 1 -C 5 alkoxy or mixtures thereof, or tetrahydro-3-thenyl; R 7 is carboxyl or C 2 -C 10 alkoxycarbonyl; R 8 is hydrogen, C 1 -C 10 alkyl, C 6 -C 10 aryl, C 7 -C 12 aralkyl or 5-indanyl; and n" is an integer of 0, 1 or 2, ##STR36## wherein R 9 is --COOR 11 wherein R 11 is hydrogen, C 1 -C 10 alkyl, C 6 -C 10 aryl, C 7 -C 12 aralkyl or 5-indanyl; each R 10 independently is hydrogen, C 1 -C 10 alkyl, phenyl, C 1 -C 5 alkoxy, C 2 -C 6 alkoxycarbonyl or carboxy; m is an integer of 1 to 4; R 9 is substituted at the 2 or 3-position; and R 10 can be substituted at the 2, 3, 4, 5 or 6-position, ##STR37## optionally substituted with at least one C 1 -C 5 alkyl, C 1 -C 5 alkoxy or mixtures thereof wherein R 12 is hydrogen, C 1 -C 10 alkyl, C 6 -C 10 aryl, C 7 -C 12 aralkyl or 5-indanyl; and r is an integer of 1, 3, 4, 5 or 6, ##STR38## wherein R 13 is hydrogen, C 1 -C 10 alkyl, C 6 -C 10 aryl, C 7 -C 12 aralkyl or 5-indanyl; Z is oxy, thio or sulfinyl; and q is an integer of 0 or 1, ##STR39## wherein R 14 is hydrogen, C 1 -C 10 alkyl, C 6 -C 10 aryl, C 7 -C 12 aralkyl or 5-indanyl; i is an integer of 0, 1 or 2; j is an integer of 0, 1 or 2; and the sum of i + j is an integer of 1 or 2; and Ar is a phenyl, naphthyl, naphthoquinonyl, anthryl, phenanthryl, pentalenyl, heptalenyl, azulenyl, biphenylenyl, as -indacenyl, S-indacenyl, acenaphthylenyl, phenylcarbonylphenyl, phenoxyphenyl, benzofuranyl, isobenzofuranyl, benzo(b)-thienyl, isobenzothienyl, oxanthrenyl, thianthrenyl, dibenzofuranyl, dibenzothienyl, phenoxathiinyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, phthalazinyl, 1,8-naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl or benzimidazolyl group each of which is unsubstituted or substituted with one or more groups selected from the group consisting of halo, nitro, cyano, hydroxy, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 2 -C 20 dialkylamino, sulfoamino, carbamoyl, C 3 -C 10 N,N-dialkylcarbamoyl, amino, C 1 -C 10 alkylamino, mercapto, C 1 -C 10 alkylthio, C 7 -C 12 aralkyl, carboxyl, C 2 -C 10 alkoxycarbonyl, C 2 -C 10 carboxyalkyl, C 1 -C 10 acylamino, C 2 -C 10 alkylcarbonyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 haloalkyl, and phenyl optionally substituted with at least one hydroxy, C 1 -C 5 alkoxy or mixtures thereof, or a C 9 -C 16 cycloalkylphenyl, C 10 -C 18 cycloalkylalkylphenyl, C 9 -C 16 cycloalkoxyphenyl, C 9 -C 16 cycloalkylthiophenyl, 5,6,7,8-tetrahydronaphthyl, C 7 -C 12 aralkyl, 9,10-dihydroanthryl, 5,6,7,8-tetrahydroanthryl, 9,10-dihydrophenanthryl, 1,2,3,4,5,6,7,8-octahydrophenanthryl, indenyl, indanyl, fluorenyl, acenaphthenyl, phenylthiophenyl, 1,2-methylenedioxyphenyl, 1,2-ethylenedioxyphenyl, chromanyl, isochromanyl, 2,3-dihydrobenzofuranyl, 1,3-dihydroisobenzofuranyl, 2,3-ethylenedioxynaphthyl, xanthenyl, thioxanthenyl, 1,2-trimethylenedioxyphenyl, 2H-chromenyl, 3,4-dehydro-1-isochromanyl, 4H-chromenyl, indolinyl, isoindolinyl, 1,2,3,4-tetrahydroquinolyl, or 1,2,3,4-tetrahydroisoquinolyl group each of which is unsubstituted or substituted with one or more groups selected from the group consisting of halo, nitro, cyano, hydroxy, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 2 -C 20 dialkylamino, sulfoamino, carbamoyl, C 3 -C 10 N,N-dialkylcarbamoyl, amino, C 1 -C 10 alkylamino, mercapto, C 1 -C 10 alkylthio, C 7 -C 12 aralkyl, C 2 -C 10 alkoxycarbonyl, C 2 -C 10 carboxyalkyl, C 1 -C 10 acylamino, C 2 -C 10 alkylcarbonyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 haloalkyl, oxo and phenyl optionally substituted with at least one hydroxy, C 1 -C 5 alkoxy or mixtures thereof.