Mitsubishi Chemical Industries Limited

Other

Shosuke Okamoto

Mitsubishi Chemical Corporation

Mitsubishi Kasei Corporation

Ryoji Kikumoto

Shinji Tonomura

Kazuo Ohkubo

Yoshikuni Tamao

Tohru Tezuka

Akiko Hijikata

Akihiro Tobe

Harukazu Fukami

Yoshikuno Tamao

Hidenobu Ikoma

Kunihiro Ninomiya

Mamoru Sugano

Issei Nitta

Mitsuo Egawa

Hiroto Hara

Kenichiro Nakao

Shinichiro Fujimori

Shinya Inoue

Tomoshi Yamazaki

Akira Maruyama

Akiko Okunomiya

Kazuo Honda

Masanori Osakabe

A method for preparing N.sup.2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-N.sup.G -nitro-L-arginine which comprises the step of condensing N.sup.G -nitro-L-arginine and 3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl chloride. The method achieves an extremely efficient and high yield preparation of N.sup.2 -arylsulfonyl-L-arginineamides that are useful as active ingredients of medicaments. Also provided is a novel N.sup.2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-N.sup.G -nitro-L-arginine compound which can be used as synthetic intermediate for the manufacture of (2R,4R)-4-methyl-1-�N.sup.2 -(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl!-2-piperidine -carboxylic acid.

Method for preparing N.sup.2 -arylsulfonyl-L-argininamides

Disclosed herein is a fibrinolysis-enhancing agent comprising, as an effective ingredient, an N.sup.2 -arylsulfonyl-L-arginine amide represented by the general formula (I): ##STR1## wherein R.sup.1 is a group of the formula: ##STR2## where R.sup.3 is an alkyl group having 3 to 5 carbon atoms or an alkoxyalkyl group having 2 to 4 carbon atoms and R.sup.4 is an alkyl group having 1 to 3 carbon atoms; and R.sup.2 is a group of the formula: ##STR3## where R.sup.5 and R.sup.6 are independently hydrogen atom, methyl group or methoxy group provided that they cannot be hydrogen atoms simultaneously, and R.sup.7 is an alkyl group having 1 to 3 carbon atoms; or a salt thereof. The agent is used in combination with a plasminogen activator.

Fibrinolysis-enhancing agents

A method of suppressing vasoconstriction in a warm-blooded animal which comprises administering to said warm-blooded animal an effective amount of a serotonin antagonist compound of the formula (I): ##STR1## wherein: R.sup.1 is hydrogen, halo, C.sub.1 -C.sub.5 alkoxy or C.sub.2 -C.sub.6 dialkyl amino;

Serotonin antagonist

A novel sulfone compound represented by the general formula (I) ##STR1## wherein R.sup.1 is cyclohexyl, phenyl; or a phenyl substituted with a group selected from nitro, C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy and halogen; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are respectively hydrogen, halogen, cyano or carbonyl, wherein R.sup.1 and R.sup.2 may form an o-phenylene or an o-phenylene substituted with at least one group selected from nitro C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy and halogen; X is oxygen or methylkene; Y is -(CH.sub.2).sub.n --, wherein n is an integer of 0, 5 or 6, or ##STR2## wherein m is an integer 1-3; R.sup.6 is hydrogen, C.sub.1 -C.sub.3 alkyl, .omega.-alkylaminoalkyl, wherein each alkyl has 1-3 carbon atoms, or .omega.-dialkylaminoalkyl, wherein each alkyl has 1-3 carbon atoms; R.sup.7 is hydrogen or C.sub.1 -C.sub.3 alkyl; and R.sup.6 and R.sup.7 may form a ring together with N, or ##STR3## wherein R.sup.8 is hydrogen, C.sub.1 -C.sub.3 hydroxyalkyl or phenyl; or a pharmaceutically acceptable salt thereof is disclosed. The compound has anti-ulcer effect.

Arylsulfone compounds as anti-ulcer agents

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

A novel sulfone compound represented by the general formula (I) ##STR1## wherein R.sup.1 is cyclohexyl, phenyl; or a phenyl substituted with a group selected from nitro, C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy and halogen; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are respectively hydrogen, halogen, cyano or carbonyl, wherein R.sup.1 and R.sup.2 may form an o-phenylene or an o-phenylene substituted with at least one group selected from nitro C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy and halogen; X is oxygen or methylene; Y is --(CH.sub.2).sub.n --, wherein n is an integer of 0, 5 or 6, or ##STR2## wherein m is an integer 1-3; R.sup.6 is hydrogen, C.sub.1 -C.sub.3 alkyl, .omega.-alkylaminoalkyl, wherein each alkyl has 1-3 carbon atoms, or .omega.-dialkylaminoalkyl, wherein each alkyl has 1-3 carbon atoms; R.sup.7 is hydrogen or C.sub.1 -C.sub.3 alkyl; and R.sup.6 and R.sup.7 may form a ring together with N, or ##STR3## wherein R.sup.8 is hydrogen, C.sub.1 -C.sub.3 hydroxyalkyl or phenyl; or a pharmaceutically acceptable salt thereof is disclosed. The compound has anti-ulcer effect.

O-aminoalkylene (or aminoalkyleneoxy) phenylsulfone compounds having

A phenylpiperazine derivative according to the present invention has the following general formula [I]: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen or alkoxy group having 1 to 3 carbon atoms, or

Phenylpiperazine derivatives and their acid addition salts

This invention relates novel thieno[2,3-d]pyrimidine derivatives represented by the following general formula (I): ##STR1## or salts thereof; wherein R.sup.1 and R.sup.2 independently represent hydrogen, halogen or alkyl group having 1 to 6 carbon atoms; or R.sup.1 and R.sup.2 may concatenate to form a cycloalkylene group having 5 or 6 ring carbon atoms; R.sup.3 and R.sup.4 independently represent hydrogen or alkyl group having 1 to 6 carbon atoms; R.sup.5 represents a member selected from

Thieno[2,3-d]pyrimidine derivatives and salts thereof

Alkylenedioxybenzene derivatives are prepared and found to be useful as pharmaceutical agents, particularly as hypotensives.

Alkylenedioxybenzene and acid addition salts thereof useful as

Alkylenedioxybenzene derivatives and acid addition salts thereof

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

A piperazine derivative according to the present invention has the following general formula [I]: ##STR1## wherein R.sup.1 is --OH, --OR.sup.3, --SR.sup.3, --SOR.sup.3 or --SO.sub.2 R.sup.3 wherein R.sup.3 is alkyl group having 1 to 3 carbon atoms;

Piperazine derivatives and their acid addition salts

(3-Aminopropoxy)bibenzyl derivatives are prepared and found useful as pharmaceutical agents, particularly as inhibitors of platelet aggregation.

Pharmaceutically active (3-cyclic aminopropoxy)bibenzyls as inhibitors

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

Growing community of inventors

Machida, Japan

Ryoji Kikumoto