Hypotensive peptides and their use

Claim 1

Compounds of formula (I): ##STR36## wherein: R 1 represents a C 1 -C 4 alkyl group having: (a) an amino or protected amino substituent on its α-carbon atom and (b) a phenyl or naphthyl group, a 5- or 6-membered heterocyclic group having one or more of hetero atoms selected from nitrogen, oxygen and sulfur atoms, a 3-indolinyl group or a 1,2,3,4-tetrahydro-β-carbolin-3-yl group, said R 1 C0-- having one or more substituents selected from an amino group and a protected amino group; or R 1 represents a 1,2,3,4-tetrahydro-β-carbolin-3-yl group or a 1,2,3,4-tetrahydro-β-carbolin-1-yl group; But represents a butyl group selected from the isobutyl and sec-butyl groups; X represents the formyl group or, a group of formula --CH(R 2 )--Y wherein R 2 is a hydrogen atom, an alkyl group of 1 to 8 carbon atoms or a substituted alkyl group of 1 to 8 carbon atoms and having at least one substituent selected from a hydroxy, mercapto, amino, carbamoyl, formyl, phenyl, naphthyl or 5- or 6-membered heterocyclic group having one or more of hetero atoms of N, O and S, and Y is hydroxy, mercapto or formyl; and the carbon atoms marked with (S) are of the S-configuration; provided that R 1 does not represent the benzyloxycarbonyl-L-phenylalanyl group or the benzyloxycarbonyl-L-prolyl-L-phenylalanyl group when X represents the formyl group; and pharmaceutically acceptable salts and esters thereof.

Claim 14

A method of treating angiotensin-induced hypertension in a mammal, by administering to said mammal an effective amount of a renin inhibitor, wherein said renin inhibitor is selected from the group consisting of compounds of formula (I): ##STR41## wherein: R 1 represents a C 1 -C 4 alkyl group having: (a) an amino or protected amino substituent on its α-carbon atom and (b) a phenyl or naphthyl group, a 5- or 6-membered heterocyclic group having one or more of hetero atoms selected from nitrogen, oxygen and sulfur atoms, a 3-indolinyl group or a 1,2,3,4-tetrahydro-β-carbolin-3-yl group, said R 1 CO-- having one or more substituents selected from an amino group and a protected amino group; or R 1 represents a 1,2,3,4-tetrahydro-β-carbolin-3-yl group or a 1,2,3,4-tetrahydro-β-carbolin-1-yl group; But represents a butyl group selected from the isobutyl and sec-butyl groups; X represents the formyl group or, a group of formula --CH(R 2 )--Y wherein R 2 is a hydrogen atom, an alkyl group of 1 to 8 carbon atoms or a substituted alkyl group of 1 to 8 carbon atoms and having at least one substituent selected from a hydroxy, mercapto, amino, carbamoyl, formyl, phenyl, naphthyl or 5- or 6-membered heterocyclic group having one or more of hetero atoms of N, O and S, and Y is hydroxy, mercapto or formyl; and the carbon atoms marked with (S) are of the S-configuration; provided that R 1 does not represent the benzyloxycarbonyl-L-phenylalanyl group or the benzyloxycarbonyl-L-prolyl-L-phenylalanyl group when X represents the formyl group; and pharmaceutically acceptable salts and esters thereof.

Claim 15

A method of treating angiotensin-induced hypertension in a mammal, by administering to said mammal an effective amount of a renin inhibitor, wherein said renin inhibitor is selected from the group consisting of compounds of formula (I): ##STR41## wherein: R 1 represents a C 1 -C 4 alkyl group having: (a) an amino or protected amino substituent on its α-carbon atom and (b) a phenyl or naphthyl group, a 5- or 6-membered heterocyclic group having one or more of hetero atoms selected from nitrogen, oxygen and sulfur atoms, a 3-indolinyl group or a 1,2,3,4-tetrahydro-β-carbolin-3-yl group, said R 1 CO-- having one or more substituents selected from an amino group and a protected amino group; or R 1 represents a 1,2,3,4-tetrahydro-β-carbolin-3-yl group or a 1,2,3,4-tetrahydro-β-carbolin-1-yl group; But represents a butyl group selected from the isobutyl and sec-butyl groups; X represents the formyl group or, a group of formula --CH(R 2 )--Y wherein R 2 is a hydrogen atom, an alkyl group of 1 to 8 carbon atoms or a substituted alkyl group of 1 to 8 carbon atoms and having at least one substituent selected from a hydroxy, mercapto, amino, carbamoyl, formyl, phenyl, naphthyl or 5- or 6-membered heterocyclic group having one or more of hetero atoms of N, O and S, and Y is hydroxy, mercapto or formyl; and the carbon atoms marked with (S) are of the S-configuration; provided that R 1 does not represent the benzyloxycarbonyl-L-phenylalanyl group or the benzyloxycarbonyl-L-prolyl-L-phenylalanyl group when X represents the formyl group; and pharmaceutically acceptable salts and esters thereof.

Claim 18

A method as claimed in any one of claims 14, 15 or 13, wherein the acyl group represented by R 1 CO-- is selected from the acetyl, propionyl, pivaloyo, benzoyl, 2-methoxycarbonylbenzoyl, 1-naphthoyl, 2-naphthoyl, phenylacetyl, benzyloxycarbonyl, phenylalanyl, N-(benzyloxycarbonyl)phenylalanyl, alpha-(benzyloxycarbonylamino)phenylacetyl, N-(4-phenylbutyryl)phenylalanyl, 2-hydroxy-3-phenylpropionyl, N-(benzyloxycarbonyl)-tyrosyl, N-(2-nitrophenylthio)phenylalanyl, N-(3-nitro-2-pyridylthio)phenylalanyl, 2-benzyloxycarbonylamino-3-(1-naphthoyl)propionyl, 2-benzyloxycarbonylamino-3-(2-naphthoyl)propionyl, nicotinyl, 2-pyridinecarbonyl, N-benzyloxycarbonyl-3-(3-quinolyl)-L-alanyl and N-benzyloxycarbonyl-3-(8-quinolyl)-L-alanyl groups, and the groups having the formulae: ##STR44## in which Boc represents the t-butoxycarbonyl group and Z represents the benzyloxycarbonyl group.

Claim 19

A method as claimed in any one of claims 14, 15 or 13, wherein the group represented by X is selected from the formyl, hydroxymethyl, formylmethyl, 2-formyl-1-hydroxyethyl, 1,2-dihydroxyethyl, 1,3-dihydroxypropyl, 2-hydroxy-1-mercaptoethyl, phosphono, hydroxo(2-hydroxyethyl)oxophosphorio and (formylmethyl)hydroxooxophosphorio groups and groups of formulae ##STR45## in which n represents an integer from 2 to 8.