Mitsubishi Chemical Industries Limited

Other

Shosuke Okamoto

Shinji Tonomura

Ryoji Kikumoto

Kazuo Ohkubo

Tohru Tezuka

Akiko Hijikata

Yoshikuni Tamao

Yoshikuno Tamao

Akihiro Tobe

Hidenobu Ikoma

Akira Maruyama

Akiko Okunomiya

Kazuo Honda

Hyogi Kikumoto

Kazdo Ohkubo

Novel arginine derivatives represented by the general formula ##STR1## wherein R.sup.1 stands for a naphthalenesulfonyl, a naphthalenecarbonyl, a 1,2,3,4-tetrahydronaphthalenesulfonyl, a 1,2,3,4-tetrahydronaphthalenecarbonyl, a dioxa b-6,7-naphthalenesulfonyl, a dioxa b-6,7-naphthalenecarbonyl, a 1,2,3,4-tetrahydro-8-quinolinesulfonyl, a 1,2,3,4-tetrahydro-8-quinolinecarbonyl, a dibenzofuransulfonyl, a dibenzofurancarbonyl, a fluorenesulfonyl, a fluorenecarbonyl, a dibenzothiophenesulfonyl or a dibenzothiophene, and R.sup.2 stands for a piperidino or a piperazino are disclosed. These arginine derivatives and their pharmaceutically acceptable salts have trypsin-inhibiting activity and useful as a pancreatitis remedy.

Arginine derivatives and pharmaceutically acceptable acid addition salts

N.sup.2 -dansyl-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 group consisting of (1) alkoxy, alkenyloxy, alkynyloxy, and cycloalkoxy, respectively, containing not more than 10 carbon atoms, aralkyl of not more than 15 carbon atoms, tetrahydrofurfuryloxy, and alkoxy of not more than 10 carbon atoms substituted with an alkoxy group of not more than 10 carbon atoms, halogen or nitro; (2) ##STR2## wherein R.sub.1 and R.sub.2 are members selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, alkenyl, and alkyl, wherein said member has no more than 10 carbon atoms, and wherein said alkyl may be substituted with a member selected from the group consisting of alkoxy, alkoxycarbonyl, arylcarbamoyl, acyl, acyloxy, N,N-polymethylenecarbamoyl, respectively, containing not more than 10 carbon atoms, and carboxyl; and (2) ##STR3## wherein Z is a divalent group containing up to 10 carbon atoms, which consists of more than one group selected from the group consisting of methylene --CH.sub.2, monosubstituted methylene ##STR4## wherein R.sub.3 is selected from the group 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 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 group 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, phenylene ##STR9## and carbonyl ##STR10## which completes the ring together with the said methylene, mono-substituted methylene or disubstituted methylene.

N.sup.2 -dansyl-L-arginine derivatives, and the pharmaceutically

2-Substituted-1-(omega-aminoalkoxy)benzenes are prepared and found useful as pharmaceutical agents, particularly as antidepressants.

Pharmaceutically active 2-substituted-1-(omega-aminoalkoxy)benzenes

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 -dansyl-L-arginine esters and amides or the acid addition salts thereof with a pharmaceutically acceptable acid have been found to be effective as pharmaceutical agents for the inhibition and suppression of thrombosis.

N.sup.2 -Dansyl-L-arginine derivatives, and the pharmaceutically

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 acceptable

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 -naphthalenesulfonyl-L-arginine esters and amides and the pharmaceutically acceptable acid addition salts thereof which have antithrombotic properties.

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

N.sup.2 -substituted-L-arginine esters and amides, and the pharmaceutically acceptable acid addition salts thereof have been found to be effective as pharmaceutical agents for the inhibition and suppression of thrombosis.

N.sup.2 -Substituted-L-arginine derivatives and the pharmaceutically

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

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

Growing community of inventors

Tokyo, Japan

Shinji Tonomura