Mitsubishi Chemical Industries Limited

Other

Shosuke Okamoto

Yoshikuno Tamao

Ryoji Kikumoto

Shinji Tonomura

Kazuo Ohkubo

Tohru Tezuka

Akiko Hijikata

N.sup.2 -naphthalenesulfonyl-L-arginine amides having the formula ##STR1## or the acid addition salts thereof with a pharmaceutically acceptable acid wherein R.sub.1 is alkenyl of not more than 10 carbon atoms, or substituted alkyl containing not more than 20 carbon atoms wherein said substituent is a member selected from the class consisting of alkoxy, alkoxycarbonyl, arylcarbamoyl acyl, acyloxy, N,N-polymethylenecarbamoyl and carboxy, and R.sub.2 is aryl, cycloalkyl, aralkyl or cycloalkylalkyl, respectively containing not more than 15 carbon atoms and R' is 1-naphthyl substituted with a member selected from the class consisting of 2-dialkylamino, 3-dialkylamino, 4-dialkylamino, 6-dialkylamino, 7-dialkylamino, 8-dialkylamino, respectively containing not more than 20 carbon atoms, and 5-dialkylamino containing 3-20 carbon atoms; or 2-naphthyl substituted with dialkylamino containing not more than 20 carbon atoms.

N.sup.2 -Naphthalenesulfonyl-L-arginine derivatives, and the

N.sup.2 -naphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof have been found to be effective as pharmaceutical agents for the inhibition and suppression of thrombosis.

N.sup.2 -arylsulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof have been found to be effective as pharmaceutical agents for the inhibition and suppression of thrombosis in mammals.

N.sup.2 -Arylsulfonyl-L-argininamides and the pharmaceutically

N.sup.2 -arylsulfonyl-l-argininamides and the pharmaceutically

N.sup.2 -arylsulfonyl-L-argininamides and the pharmaceutically

N.sup.2 -alkoxynaphthylsulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof have been found to be effective as pharmaceutical agents for the inhibition and suppression of thrombosis in mammals, and are prepared by reacting an N.sup.2 -alkoxynaphthylsulfonyl-L-arginyl halide with an N-substituted amino acid or an ester thereof.

N.sup.2 -alkoxynaphthylsulfonyl-L-argininamides and the pharmaceutically

N.sup.2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof have been found to be effective as pharmaceutical agents for the inhibition and suppression of thrombosis in mammals.

N.sup.2 -alkoxynaphthalenesulfonyl-L-argininamides and the

N.sup.2 -naphthalenesulfonyl-L-arginine esters and amides having the formula ##STR1## or the acid addition salts thereof with a pharmaceutically acceptable acid, wherein R is selected from the class consisting of (1) alkoxy, alkenyloxy, cycloalkoxy and halogenated alkoxy, aralkyloxy, and alkoxy substituted with an alkoxy group; ##STR2## wherein R.sub.1 and R.sub.2 are members selected from the class consisting of hydrogen, alkyl, aryl, alkenyl and cycloalkyl, and aralkyl and cycloalkylalkyl, and substituted alkyl, said substituent being selected from the class consisting of alkoxy, alkoxycarbonyl, acyl, acyloxy, arylcarbamoyl and N,N-polymethylenecarbamoyl, and carboxy; and ##STR3## wherein Z is a divalent group containing up to 10 carbon atoms, which consists of more than one group selected from the class consisting of methylene, monosubstituted methylene; and disubstituted methylene, and which may further contain at least one member selected from the class consisting of oxy-O-, thio --S--, cycloalkylene, imino, alkyl-substituted imino, acyl-substituted imino, and phenylene, which may be arranged in any order and complete the ##STR4## ring together with the said methylene, monosubstituted methylene or disubstituted methylene, and R' is a member selected from the class consisting of 1-naphthyl substituted 2-, 3-, 4-, 6-, 7- or 8-dialkylamino, respectively, containing not more than 20 carbon atoms, and 1-naphthyl substituted with 5-dialkylamino containing 3 - 20 carbon atoms, 2-naphthyl substituted dialkylamino containing not more than 20 carbon atoms.

N.sup.2 -naphthalenesulfonyl-L-arginine esters and amides having the formula ##STR1## or the acid addition salts thereof with a pharmaceutically acceptable acid, wherein R is selected from the class consisting of (1) alkoxy, alkenyloxy, cycloalkoxy and halogenated alkoxy, respectively containing not more than 10 carbon atoms, aralkyloxy of not more than 15 carbon atoms, and alkoxy of not more than 10 carbon atoms substituted with an alkoxy group of not more than 10 carbon atoms; ##STR2## wherein R.sub.1 and R.sub.2 are members selected from the class consisting of hydrogen, alkyl, aryl, alkenyl and cycloalkyl, respectively containing not more than 10 carbon atoms, and aralkyl and cycloalkylalkyl, respectively containing not more than 15 carbon atoms, and substituted alkyl containing not more than 20 carbon atoms, said substituent being selected from the class consisting of alkoxy, alkoxycarbonyl, acyl, acyloxy, arylcarbamoyl and N,N-polymethylenecarbamoyl, respectively containing not more than 10 carbon atoms, and carboxy; and (3) ##STR3## wherein Z is a divalent group containing up to 10 carbon atoms, which consists of more than one group selected from the class consisting of methylene --CH.sub.2 --, monosubstituted methylene ##STR4## wherein R.sub.3 is selected from the class consisting of alkyl, acyl, alkoxy, and alkoxycarbonyl, respectively containing not more than 10 carbon atoms, and carbamoyl; and disubstituted methylene ##STR5## wherein R.sub.4 and R.sub.5 are alkyl groups of not more than 10 carbon atoms, and which may further contain at least one member selected from the class consisting of oxy--O--, thio --S--, cycloalkylene of not more than 10 carbon atoms, imino ##STR6## alkyl-substituted imino ##STR7## wherein R.sub.6 is an alkyl group of not more than 10 carbon atoms, acyl-substituted imino ##STR8## wherein R.sub.7 is an alkyl group of not more than 10 carbon atoms, and phenylene ##STR9## which may be arranged in any order and complete the ##STR10## ring together with the said methylene, monosubstituted methylene or disubstituted methylene; and R' is a member selected from the class consisting of 5,6,7,-8-tetrahydro-1-naphthyl, 5,6,7,8-tetrahydro-2-naphthyl, 1-naphthyl, 2-naphthyl, 1-naphthyl substituted alkoxy or alkoxycarbonyloxy, respectively containing not more than 10 carbon atoms; and 2-naphthyl substituted with alkoxy or alkoxycarbonyloxy, respectively containing not more than 10 carbon atoms.

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Yokohama, Japan

Yoshikuno Tamao