Banyu Pharmaceutical Co. Ltd

Shugo Atsuumi

Seiichi Tanaka

Kenji Matsuyama

Hajime Morishima

Masato Nakano

Yutaka Koike

Yutaka Kokie

An N-acylamino acid derivative of the formula: ##STR1##

N-acylamino acid derivatives and their use

An N-acylamino acid derivative of the formula: ##STR1## wherein each of R.sup.1, R.sup.2, R.sup.4 and R.sup.6 is hydrogen lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl or a monocyclic or bicyclic heterocyclic group containing from to 4 hetero atoms; each of R.sup.3 and R.sup.5 is hydrogen or lower alkyl; A is --CH(OH)--(CH.sub.2).sub.q R.sup.7 wherein R.sup.7 is hydrogen, lower alkyl, cycloalkyl, cyloalkylalkyl, aryl, aralkyl, a monocyclic or bicyclic heterocyclic group containing from to 4 hereto atoms or --E--R.sup.10 wherein E is --S(O).sub.i -- wherein i is 0, 1 or 2, oxygen, --NR.sup.11 -- wherein R.sup.11 is hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, or ##STR2## wherein each of R.sup.12 and R.sup.13 is hydrogen, lower alkyl cycloalkyl, cycloalkylalkyl, aryl or aralkyl, and R.sup.10 is hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms provided that when R.sup.10 is hydrogen, i is 0, and a is an integer of from 0 to 5; or --CH.sub.2 --CHR.sup.8 --CO--R.sup.9 wherein R.sup.8 is hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms, and R.sup.9 is hydroxyl, --OX wherein X is alkyl, aryl, lower alkoxycarbonyloxyalkyl or 1-phthalidyl, or --N(Y.sup.1) (Y.sup.2) wherein each of Y.sup.1 and Y.sup.2 is hydrogen, lower alkyl, aryl, aralkyl or cycloalkyl, or Y and.sup.1 and Y.sup.2 form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may contain a further hereto atom; m is 0, 1 or 2; and n is an integer of from 1 to 5, provided that when R.sup.1 is hydrogen, m is 0; or a salt thereof, which is useful as hypotensive drugs.

The present invention provides an N-substituted acylamino acid compound of the formula: ##STR1## a process for their production and pharmaceutical uses, and intermediates useful for their production.

N-substituted acylamino acid compounds, process for their production and

An N-acylamino acid derivative of the formula: ##STR1## wherein each of R.sup.1, R.sup.2, R.sup.4 and R.sup.6 is hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms; each of R.sup.3 and R.sup.5 is hydrogen or lower alkyl; A is --CH(OH)--(CH.sub.2).sub.q R.sup.7 wherein R.sup.7 is hydrogen, lower alkyl, cycloalkyl, cyloalkylalkyl, aryl, aralkyl, a-monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms or --E--R.sup.10 wherein E is --S(O).sub.i -- wherein i is 0, 1 or 2, oxygen, --NR.sup.11 -- wherein R.sup.11 is hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, or ##STR2## wherein each of R.sup.12 and R.sup.13 is hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, and R.sup.10 is hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms provided that when R.sup.10 is hydrogen, i is 0, and a is an integer of from 0 to 5; or --CH.sub.2 --CHR.sup.8 --CO--R.sup.9 wherein R.sup.8 is hydrogen, lower alkyl, cycloalkyl, cycloalkylakyl, aryl, aralkyl or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms, and R.sup.9 is hydroxyl, --OX wherein, X is alkyl aryl, lower alkoxycarbonyloxyalkyl or 1-phthalidyl, or --N(Y.sup.1)(Y.sup.2 ) wherein each of Y.sup.1 and Y.sup.2 is hydrogen, lower alkyl, aryl, aralkyl or cycloalkyl, or Y.sup.1 and Y.sup.2 form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may contain a further hetero from; m is 0, 1 or 2; and n is an integer of from 1 to 5, provided that when R.sup.1 is hydrogen, m is 0; or a salt thereof, which is useful as hypotensive drugs.

N-acylamino acid derivatives

An N-acylamino acid derivative of the formula: ##STR1## wherein the substituents are herein defined, or a salt thereof, which is useful as hypotensive drugs.

An N-acylamino acid derivative of the formula: ##STR1## wherein the substituents are herein defined or a salt thereof, which is useful as hypotensive drugs.

N-acylamino acid derivatives and their pharmaceutical compositions

A 5-substituted amino-4-hydroxy-pentenoic acid or its salt represented by the formula: ##STR1## wherein each of R.sup.1 and R.sup.2 which may be the same or different is a hydrogen atom, a lower alkyl group, an aralkyl group, a lower alkoxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group or a lower alkanoyl group which may be substituted by from one to three substituents selected from the group consisting of an amino group, a hydroxyl group, a carboxyl group, an aryloxy group, an aralkyloxycarbonylamino group, a lower alkoxycarbonylamino group and a ##STR2## group (wherein each of X.sup.1 and X.sup.2 which may be the same or different is a hydrogen atom, a lower alkyl group, an aryl group or an aralkyl group, or X.sup.1 and X.sup.2 form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may further contain a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom) and which may further contain a double bond in its carbon chain, each of R.sup.3, R.sup.4 and R.sup.6 which may be the same or different is a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an aralkyl group or a residue of an acidic neutral or basic amino acid, R.sup.5 is a hydrogen atom or a lower alkyl group, R.sup.7 is a hydrogen atom, a lower alkyl, cycloalkyl, cycloalkylalkyl or aralkyl group which may be substituted by one or two hydroxyl groups or a residue of an acidic, neutral or basic amino acid, R.sup.8 is a hydroxymethyl group or a --CO--R.sup.9 group (wherein R.sup.9 is a hydroxyl group, a --OY group (wherein Y is a lower alkyl group, an aryl group, an aralkyl group, a lower alkoxyalkyl group, a lower alkanoyloxyalkyl group, a lower alkoxycarbonyloxyalkyl group, or a 1-phthalidyl group) or ##STR3## group (wherein each of Y.sup.1 and Y.sup.2 which may be the same or different is a hydrogen atom, a lower alkyl group, an aryl group, an aralkyl group or a cycloalkyl group, or Y.sup.1 and Y.sup.2 form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may further contain a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom), and each of n and m which may be the same or different is 0 or 1.

5-substituted amino-4-hydroxy-pentenoic acid derivatives and their use

A 5-substituted amino-4-hydroxy-pentanoic acid derivative having the formula: ##STR1## wherein R.sup.1 is a hydrogen atom or an N-protecting group, R.sup.2, R.sup.3 and R.sup.5 may be any of a variety of groups including the side chains of amino acid residues, R.sup.4 is a hydrogen atom or a lower alkyl group, R.sup.6 is a group which is substituted by one or two hydroxyl groups, and R.sup.7 is any of a variety of groups, including a hydroxyl group, which compounds are renin inhibitors useful as hypotensive drugs, are disclosed.

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Tokyo, Japan

Shugo Atsuumi