Ono Pharmaceutical Co., Ltd.

Hideki Aishita

Yoshinobu Arai

Masanori Kawamura

Setsuro Fujii

Hiroshi Terashima

Yasumichi Kajita

Ken Taniguchi

Minoru Wada

Heizo Kira

Akira Akimoto

Seizi Hiraku

Keiko Muryobayashi

Amino acid compounds of the formula: ##STR1## wherein the various symbols are as hereinafter described, which have inhibiting effect on enkephalinase.

3-mercapto-glutamic acid derivatives

The compounds of the formula: ##STR1## (wherein R.sup.1 is hydrogen or alkyl; R.sup.2 is carbocyclic or heterocyclic ring, unsubstituted or substituted by R.sup.3 s; R.sup.3 is halogen, trihalomethyl, hydroxy, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfornyl, cyano, nitro, or group of the formula: --C.sub.6 H.sub.4 --R.sup.4, --NR.sup.5 R.sup.6, --CO--R.sup.7, --COOR.sup.8, --CONR.sup.5 R.sup.6, --SO.sub.2 NR.sup.5 R.sup.6 or --NHCO--R.sup.7, in which R.sup.4 is hydrogen, halogen, trihalomethyl, hydroxy, alkyl or alkoxy, R.sup.5 and R.sup.6 are each hydrogen or alkyl, R.sup.7 is alkyl or phenyl substituted by R.sup.4 and R.sup.8 is hydrogen or alkyl; Z is hydrogen or group of the formula: --COR.sup.9, ##STR2## in which R.sup.9 is alkyl or phenyl substituted by R.sup.10, in which R.sup.10 is hydrogen, halogen, trihalomethyl, alkyl or alkoxy, R.sup.11 and R.sup.12 are each hydrogen, alkyl or phenyl substituted by R.sup.10, or R.sup.11 and R.sup.12 together represent alkylene and p is 1 or 2; A is phenyl or cycloalkyl substituted by R.sup.13 in which R.sup.13 is hydrogen, halogen, trihalomethyl, alkyl or alkoxy; and m is zero and n is 1 to 4 or n is zero and m is 1 to 4; and non-toxic salts thereof have inhibitory effect on enkephalinase, and therefore, are useful as analgesic, antianxiety and anticonvulsant.

Amino acid derivatives

The compounds of the formula: ##STR1## (wherein R.sup.1 is hydrogen or alkyl; R.sup.2 is carbocyclic or heterocyclic ring, unsubstituted or substituted by R.sup.3 S; R.sup.3 is halogen, trihalomethyl, hydroxy, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfornyl, cyano, nitro, or group of the formula: --C.sub.6 H.sub.4 --R.sup.4, --NR.sup.5 R.sup.6, --CO--R.sup.7, --COOR.sup.8, --CONR.sup.5 R.sup.6, --SO.sub.2 NR.sup.5 R.sup.6 or --NHCO--R.sup.7, in which R.sup.4 is hydrogen, halogen, trihalomethyl, hydroxy, alkyl or alkoxy, R.sup.5 and R.sup.6 are each hydrogen or alkyl, R.sup.7 is alkyl or phenyl substituted by R.sup.4 and R.sup.8 is hydrogen or alkyl; Z is hydrogen or group of the formula: --COR.sup.9, ##STR2## in which R.sup.9 is alkyl or phenyl substituted by R.sup.10, in which R.sup.10 is hydrogen, halogen, trihalomethyl, alkyl or alkoxy, R.sup.11 and R.sup.12 are each hydrogen, alkyl or phenyl substituted by R.sup.10, or R.sup.11 and R.sup.12 together represent alkylene and p is 1 or 2; .circle. is phenyl or cycloalkyl substituted by R.sup.13 in which R.sup.13 is hydrogen, halogen, trihalomethyl, alkyl or alkoxy; and m is zero and n is 1 to 4 or n is zero and m is 1 to 4; and non-toxic salts thereof have inhibitory effect on enkephalinase, and therefore, are useful as analgesic, antianxiety and anticonvulsant.

Novel amino acid derivatives

A method for isolating and purifying a physiologically active substance contained in a tissue or a body fluid using an insoluble type naturally occurring proteolytic enzyme inhibitor or an insoluble type proteolytic enzyme alone or in combination with the insoluble type naturally occurring proteolytic enzyme inhibitor is disclosed.

Method for purification of physiologically active substance using

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Osaka, Japan

Hideki Aishita