N-acylamino acid derivatives and their use

Claim 2

An N-acylamino acid derivative of the formula: wherein each of R¹, R², R⁴ and R⁶ which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms; each of R³ and R⁵ which may be the same or different is a hydrogen atom or a lower alkyl group; A is a -CH(OH)-(CH₂ R⁷ wherein R⁷ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cyloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms or a -E-R¹⁰ group wherein E is a -S(O) i - group wherein i is 0, 1 or 2, an oxygen atom, a -NR¹¹- group wherein R¹¹ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group, or a group wherein each of R¹² and R¹³ which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group, and R¹⁰ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms, provided that when R¹⁰ is a hydrogen atom, i is 0, and q is an integer of from 0 to 5; or a -CH₂-CHR⁸-CO-R⁹ group wherein R⁸ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containig from 1 to 4 hetero atoms selected from the group consisting of nitrogen, surfur and oxygen atoms, and R⁹ is a hydroxyl group, a -OX group wherein X is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, a lower alkoxycarbonyloxyalkyl group or a 1-phthalidyl group, or a -N(Y¹)(Y²) group wherein each of Y¹ and Y² which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted cycloalkyl group, or Y¹ and Y² form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may contain a further hetero atom selected from the group consisting of nitrogen, oxygen and sulfur atoms; m is 0, 1 or 2; and n is an integer of from 1 to 5, provided that when R¹ is a hydrogen atom, m is 0; or a salt thereof.

Claim 3

The N-acylamino acid derivative or its salt according to Claim 1, wherein A is a -CH(OH)-(CH₂ R⁷ group wherein R⁷ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms or a -E-R¹⁰ group wherein E is a -S(O) i - group wherein i is 0, 1 or 2, an oxygen atom, a -NR¹¹- group wherein R¹¹ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group, or a group wherein each of R¹² and R¹³ which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group, and R¹⁰ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms, provided that when R¹⁰ is a hydrogen atom, i is 0, and q is an integer of from 0 to 5; m is 0, 1 or 2; and n is an integer of from 1 to 5; provided when R¹ is a hydrogen atom, m is 0.

Claim 4

The N-acylamino acid derivative or its salt according to Claim 1, wherein A is a -CH₂-CHR⁸-CO-R⁹ group wherein R⁸ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms, and R⁹ is a hydroxyl group, a -OX group wherein X is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, a lower alkoxycarbonyloxyalkyl group or a 1-phthalidyl group, or a -N(Y¹)(Y²) group wherein each of Y¹ and Y² which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted cycloalkyl group, or Y¹ and Y² form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may contain a further hetero atom selected from the group consisting of nitrogen, oxygen and sulfur atoms; m is 0, 1 or 2; and n is an integer of from 1 to 5; provided when R¹ is a hydrogen atom, m is 0.

Claim 5

The N-acylamino acid derivative or its salt according to Claim 1, wherein A is a group of the formula: wherein j is 0 or 1.

Claim 6

The N-acylamino acid derivative or its salt according to Claim 4, wherein each of R¹, R², R⁴ and R⁶ which may be the same or different is a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur atoms; each of R³ and R⁵ is a hydrogen atom; m is 0, 1 or 2; and n is 1.

Claim 7

The N-acylamino acid derivative or its salt according to Claim 1, wherein R² is A is a -CH₂-CHR⁸-CO-R⁹ group wherein R⁸ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms, and R⁹ is a hydroxyl group, a -OX group wherein X is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, a lower alkoxycarbonyloxyalkyl group or a 1-phthalidyl group, or a -N(Y¹)(Y²) group wherein each of Y¹ and Y² which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted cycloalkyl group, or Y¹ and Y² form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may contain a further hetero atom selected from the group consisting of nitrogen, oxygen and sulfur atoms; m is 0, 1 or 2; and n is an integer of from 1 to 5; provided when R¹ is a hydrogen atom, m is 0.

Claim 8

The N-acylamino acid derivative or its salt according to Claim 1, which is (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-(1-­naphthylmethyl)propionyl]seryl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-(1-­ naphthylmethyl)propionyl]methionyl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-isopropylsulfonyl-2-(8-­quinolylmethyl)propionyl]leucyl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N α -[(2S)-3-isopropylsulfinyl-2-(1-­naphthylmethyl)propionyl]histidyl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S or R)-3-(2-hydroxyethyl)sulfonyl-­2-(1-naphthylmethyl)propionyl]norleucyl}amino-5-­cyclohexyl-1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-2-benzyl-3-ethylsulfonyl­propionyl]norleucyl}amino-5-cyclohexyl-1-morpholino-­2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-tert-butylsulfonyl-2-(1-­naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-[L-N-(2S)-3-[[(2S)-N-benzyloxycarbonyl-2-­pyrrolidinyl]methyl]sulfonyl-2-(1-naphthylmethyl)­propionyl]norleucyl]amino-5-cyclohexyl-1-morpholino-2,3-­pentanediol, (2S,3R,4S)-4-{L-N-[(2S or R)-3-(2-hydroxyethyl)sulfonyl-­2-(1-naphthylmethyl)propionyl]norleucyl}amino-5-­cyclohexyl-1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfinyl-2-1-­naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, N-[(2S,3R,4S)-4-{L-N-[(2R)-3-ethylsulfonyl-2-(1-­naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­2,3-dihydroxypentyl]morpholine N-oxide, (2S,3R,4S)-4-{L-N-[(2S or R)-3-cyclopentanesulfonyl-2-­benzylpropionyl]norleucyl}amino-5-cyclohexyl-1-­morpholino-2,3-pentanediol, N-[(2S,3R,4S)-4-{L-N-[(2R)-3-cyclopentanesulfonyl-2-­benzylpropionyl]norleucyl}amino-5-cyclohexyl-1-­2,3-dihydroxypentyl]morpholine N-oxide, (2RS,4S,5S)-5-{L-N-[(2S)-3-ethylsulfonyl-2-(4-­quinolylmethyl)propionyl]norleucyl}amino-2-ethyl-4-­hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N-[(2S)-3-ethylsulfonyl-2-(8-­quinolylmethyl)propionyl]norleucyl}amino-2-ethyl-4-­hydroxy-7-methyloctanoic acid isobutylamide, (2S,3R,4S)-4-{L-N-[(2S)-2-benzyl-3-furfurylsulfonyl­propionyl]norleucyl}amino-5-cyclohexyl-1-morpholino-­2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-2-(1-naphthylmethyl)-3-­pyrimidin-2-yl)thiopropionyl]norleucyl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-2-(1-naphthylmethyl)-3-­(pyrimidin-2-yl)sulfonylpropionyl]norleucyl}amino-5-­cyclohexyl-1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-2-(1-naphthylmethyl)-3-­(pyrimidin-2-yl)sulfinylpropionyl]norleucyl}amino-5-­cyclohexyl-1-morpholino-2,3 pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-2-(1-naphthylmethyl)-3-­[(2S)-2-pyrrolidinylmethyl]sulfonylpropionyl]norleucyl}­amino-5-cyclohexyl-1-morpholino-2,3-pentanediol dihydrochloride, (2S,3R,4S)-4-{L-N-[(2S)-2-benzyl-3-(pyrimidin-2-yl) sulfonylpropionyl]norleucyl}amino-5-cyclohexyl-1-­morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-O-acetyl-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]homoseryl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]homoseryl}amino-5-cyclohexyl-­2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-furfurylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­1-morpholino-2,3-pentanediol, (2RS,4S,5S)-5-{L-N-[(2R or S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-2-ethyl-4-­hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N-[(2R or S)-3-(pyrimidin-2-yl)sulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-2-ethyl-4-­hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N-[(2R or S)-3-ethylsulfonyl-2-­(2,3-ethylenedioxybenzyl)propionyl]-δ-hydroxynorvalyl}amino-­2-ethyl-4-hydroxy-7-methyloctanoic acid isobutylamide, (2S,4S,5S)-5-{L-N-[(2R or S)-3-(1-methyltetrazol-5-yl)­sulfonyl-2-(1-naphthylmethyl)propionyl]norleucyl}amino-2-­ ethyl-4-hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N-[(2S)-3-(1,3,4-thiadiazol-2-yl)thio-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-2-ethyl-­4-hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N-[(2S)-3-(pyrimidin-2-yl)thio-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-2-ethyl-­4-hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N-[(2S)-3-(pyrimidin-2-yl)sulfinyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-2-ethyl-­4-hydroxy 7-methyloctanoic acid isobutylamide, (2R or S,4S,5S)-5-{L-N-[(2R or S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-2-ethyl-­4-hydroxy-7-methyloctanoic acid 2-morpholinoethylamide, (2RS,3RS,4S)-4-{L-N-[3-ethylsulfonyl-2-(1-naphthylmethyl)­propionyl]norleucyl}amino-5-cyclohexyl-1-morpholino-2,3-­pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-(1-­naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-1-­piperidino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-(1-­naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-1-­(4-methylpiperidino)-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-6-methyl-1-­morpholino-2,3-heptanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­ 1-(2-methoxyethylamino)-2,3-pentanediol, (2RS,3R or S,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­1-methylthio-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­1-(2-hydroxyethylamino)-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­1-diethylamino-2,3-pentanediol, (2RS,3RS,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-­1-[ethyl(2-hydroxyethyl)amino]-2,3-pentanediol, (2RS,3RS,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-1-­isopropylthio-6-methyl-2,3-heptanediol, (2RS,3RS,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]norleucyl}amino-6-methyl-1-­thiomorpholino-2,3-heptanediol, (2S,3R,4S)-4-[L-N-((2R or S)-2-ethylsulfonylmethyl-4-­methylpentanoyl)norleucyl]amino-5-cyclohexyl-1-­morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2R or S)-5-ethylthio-2-(1-naphthylmethyl) pentanoyl]norleucyl}amino-5-cyclohexyl-1-­morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2R or S)-5-ethylsulfonyl-2-(1-­naphthylmethyl)pentanoyl]norleucyl}amino-5-cyclohexyl-1-­ morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-(8-­quinolylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-1-­morpholino-2,3-pentanediol, (2S,3R,4S)-4-{L-N α -[(2S)-3-ethylsulfonyl-2-(1-­naphthylmethyl)propionyl]histidyl}amino-5-cyclohexyl-1-­morpholino-2,3-pentanediol, (2RS,4S,5S)-5-{L-N-[(2R or S)-5-ethylthio-2-(1-­naphthylmethyl)pentanoyl]norleucyl}amino-2-ethyl-4-­hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N-[(2R or S)-5-ethylsulfonyl-2-(1-­naphthylmethyl)pentanoyl]norleucyl}amino-2 ethyl-4-­hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N α -[(2RS)-3-ethylsulfonyl-2-­(1-naphthylmethyl)propionyl]-N im -triphenylmethyl­histidyl}amino-2-ethyl-4-hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N α -[(2S)-3-ethylsulfonyl-­2-(1-naphthylmethyl)propionyl]histidyl}amino-2-ethyl-4-­hydroxy-7-methyloctanoic acid isobutylamide, (2RS,4S,5S)-5-{L-N α -[2(S)-3-ethylsulfonyl-2-(8-­quinolylmethyl)propionyl]histidyl}amino-2-ethyl-4-­hydroxy-7-methyloctanoic acid isobutylamide, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-[(5 6,7,8-­tetrahydro-1-naphthyl)methyl]propionyl]norleucyl}amino-5-­cyclohexyl-1-morpholino-2,3-pentanediol, N-[(2S,3R,4S)-4-[L-N-[(2S)-3-ethylsulfonyl-2-(1-­naphthylmethyl)propionyl]norleucyl]amino-5-cyclohexyl-­ 2,3-dihydroxypentyl]piperidine N-oxide, N-[(2S,3R,4S)-4-­[L-N-[(2S)-3-ethylsulfonyl-2-(1-naphthylmethyl)­propionyl]norleucyl]amino-5-cyclohexyl-2,3-­dihydroxypentyl]-N-methyl morpholinonium iodide, (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-(3-tolylmethyl)­propionyl]norleucyl}amino-5-cyclohexyl-1-morpholino-2,3-­pentanediol or (2S,3R,4S)-4-{L-N-[(2S)-3-ethylsulfonyl-2-­(2-tolylmethyl)propionyl]norleucyl}amino-5-cyclohexyl-1-­morpholino-2,3-pentanediol.

Claim 9

A compound of the formula: wherein each of R¹ and R² which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms; R¹⁴ is a carboxyl group, a reactive derivative of a carboxyl group or a protected carboxyl group; m is 0, 1 or 2; and n is an integer of from 1 to 5; provided that when R¹ is a hydrogen atom, m is 0.

Claim 10

A compound of the formula: wherein each of R¹ and R² which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms; R¹⁴ is a carboxyl group, a reactive derivative of a carboxyl group or a protected carboxyl group; m is 0, 1 or 2; and n is an integer of from 1 to 5; provided that when R¹ is a hydrogen atom, m is 0.

Claim 11

A compound of the formula: wherein R⁵ is a hydrogen atom or a lower alkyl group; R⁶ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms; R⁷ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms or a -E-R¹⁰ group, wherein E is a -S(O) i -group wherein i is 0, 1 or 2, an oxygen atom, a -NR¹¹-group wherein R¹¹ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group, or wherein each of R¹² and R¹³ which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group, and R¹⁰ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms, provided that when R¹⁰ is a hydrogen atom, i is 0; R¹⁵ is a hydrogen atom or a protecting group for an amino group, each of R¹⁶ and R¹⁷ which may be the same or different is a hydrogen atom or a protecting group for a hydroxyl group; and q is an integer of from 0 to 5.

Claim 12

A compound of the formula: wherein R⁵ is a hydrogen atom or a lower alkyl group; R⁶ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms; R⁷ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms or a -E-R¹⁰ group, wherein E is a -S(O) i -group wherein i is 0, 1 or 2, an oxygen atom, a -NR¹¹-group wherein R¹¹ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group, or wherein each of R¹² and R¹³ which may be the same or different is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group, and R¹⁰ is a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkylalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a monocyclic or bicyclic heterocyclic group containing from 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms, provided that when R¹⁰ is a hydrogen atom, i is 0; R¹⁵ is a hydrogen atom or a protecting group for an amino group, each of R¹⁶ and R¹⁷ which may be the same or different is a hydrogen atom or a protecting group for a hydroxyl group; and q is an integer of from 0 to 5.

Claim 13

A process for producing an N-acylamino acid derivative of the formula I as defined in Claim 1 or its salt, which comprises condensing an N-acylamino acid of the formula: wherein R¹, R², R³, R⁴, m and n are as defined in Claim 1, or a reactive derivative at the carboxyl group thereof with an amine of the formula: wherein R⁵, R⁶ and A are as defined in Claim 1, or condensing a carboxylic acid of the formula: wherein R¹, R², m and n are as defined in Claim 1, or a reactive derivative at the carboxyl group thereof with an amino acid amide of the formula: wherein R³, R⁴, R⁵, R⁶ and A are as defined in Claim 1.

Claim 14

A hypotensive drug comprising an effective amount of an N-acylamino acid derivative of the formula I as defined in Claim 1 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.