Peptide, production and use thereof

Claim 2

The peptide as claimed in claim 1 wherein R₁ is (i) a straight or branched C₁₋₁₀ alkyl group which may be substituted, (ii) a C₃₋₁₀ cycloalkyl group which may be substituted, (iii) a straight or branched C₁₋₈ alkoxy group which may be substituted, (iv) a C₆₋₁₅ aromatic hydrocarbon group which may be substituted, (v) a 5- to 6- membered aromatic heterocyclic group which contains 1 to 4 hetero atoms of O,S and N which may be substituted or the group as condensed with another aromatic ring or (vi) a substituted amino group.

Claim 3

The peptide as claimed in claim 2 wherein the straight or branched C₁₋₁₀ alkyl group may be substituted by 1 to 3 substituents selected from the group consisting of a C₃₋₈ cycloalkyl group, a halogen atom, a C₁₋₆ alkoxy group, a C₁₋₆ alkylthio group, a C₁₋₆ alkoxycarbonyl group, a C₆₋₁₂ aromatic hydrocarbon group which may be substituted by a halogen atom, hydroxy group, C₁₋₃ alkoxy group or C₁₋₃ alkyl group and a 5- to 10- membered aromatic heterocyclic group.

Claim 4

The peptide as claimed in claim 2 wherein the C₃₋₁₀ cycloalkyl group may be substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl group, a halogen atom, a C₁₋₆ alkoxy group, a C₁₋₆ alkylthio group and a C₁₋₆ alkoxycarbonyl group, or the cycloalkyl group as condensed with another ring.

Claim 5

The peptide as claimed in claim 2 wherein the straight or branched C₁₋₈ alkoxy group may be substituted by 1 to 3 substituents selected from the group consisting of a C₃₋₈ cycloalkyl group, a C₁₋₆ alkoxy group and a C₁₋₆ alkoxy carbonyl group.

Claim 6

The peptide as claimed in claim 2 wherein the C₆₋₁₅ aromatic hydrocarbon group may be substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxy group, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, a carboxyl group, a C₁₋₆ alkylcarbonyl group and a C₁₋₆ alkoxycarbonyl group.

Claim 7

The peptide as claimed in claim 2 wherein the 5- to 6-membered aromatic heterocyclic group which contains 1 to 4 hetero atoms of O,S and N or the group as condensed with another aromatic ring, which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxy group, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, a carboxyl group, a C₁₋₆ alkylcarbonyl group and a C₁₋₆ alkoxycarbonyl group.

Claim 8

The peptide as claimed in claim 2 wherein the substituted amino group is a group represented by R₇NH- or R₈R₉N- wherein R⁷, R⁸ and R⁹ independently represent (i) a C₄₋₁₀ alkyl group, (ii) a C₅₋₁₀ cycloalkyl group, (iii) a C₆₋₁₂ aromatic hydrocarbon group or (iv) a 5- to 10- membered aromatic heterocyclic group which may be substituted or the group as condensed with another aromatic ring, and R⁸ and R⁹ may bind together to form a ring.

Claim 9

The peptide as claimed in claim 8 wherein each of R₇, R₈ and R₉ independently is (i) a C₄₋₁₀ alkyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a C₃₋₈ cycloalkyl group, a C₁₋₆ alkoxy group, a C₁₋₆ alkylthio group, a hydroxy group, a carboxyl group, a C₁₋₆ alkylcarbonyl group, a C₆₋₁₂ aromatic hydrocarbon group which may be substituted by a halogen atom, a hydroxy group, a C₁₋₃ alkoxy group or a C₁₋₃ alkyl group, and a 5- to 10- membered aromatic heterocyclic group which contains 1 to 4 hetero atoms of O,S and N, (ii) a C₅₋₁₀ cycloalkyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, a C₁₋₆ alkylthio group, a hydroxy group, a carboxyl group and a C₁₋₆ alkylcarbonyl group, (iii) a C₆₋₁₂ aromatic hydrocarbon group which may be substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, a hydroxy group, a carboxyl group and a C₁₋₆ alkylcarbonyl group, or (iv) a 5- to 10- membered aromatic heterocyclic group which contains 1 to 4 hetero atoms of O,N and S or the group as condensed with another aromatic ring wherein a carbon atom which may be substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl, C₁₋₆ alkoxy, hydroxyl, carboxyl and C₁₋₆ alkylcarbonyl group, and a nitrogen atom which may be substituted by 1 to 3 C₁₋₆ alkyl groups, and R₈ and R₉ may bind together to form a 5- to 13- membered nitrogen-containing heterocyclic ring which may have 1 or 2 hetero atoms such as oxygen atom and sulfur atom, the said 5- to 13- membered nitrogen-containing heterocyclic ring being optionally substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl group, a phenyl group, a halogen atom, a nitro group, a cyano group, a hydroxy group, a C₁₋₄ alkoxy group, a C₁₋₄ alkylthio group, an amino group, a mono- or di-C₁₋₄ alkylamino group, a C₁₋₄ alkylcarbonylamino group, a C₁₋₄ alkylsulfonylamino group, a C₁₋₄ alkoxycarbonyl group, a carboxyl group, a C₁₋₆ alkylcarbonyl group, a C₁₋₄ alkylcarbonyloxy group and a 5- or 6- membered heterocyclic group having 1 to 4 hetero atoms such as O,S and N.

Claim 10

The peptide as claimed in claim 9 wherein the 5- to 13- membered nitrogen-containing heterocyclic ring which may have 1 or 2 hetero atoms such as oxygen atom and sulfur atom is a pyrrolidinyl, piperidinyl, hexamethyleneiminyl, heptamethyleneiminyl, oxazolidinyl, morphonyl, thiazolidinyl, thiomorphonyl, imidazolidinyl, piperazinyl, pyrrolyl, 1,2-dihydropyridinyl, 1-4-dihydropyridinyl, 1,2,3,6-tetrahydropyridinyl, 2-oxazolidonyl, 2-thiazolidonyl, imidazolyl, 1,4,5,6-tetrahydropyrimidinyl, 2,3-dihydro-1H-indolyl, 1,2,3,4-tetrahydroquinolinyl, 2,3,4,5-tetrahydro-1H-1-benzazepinyl, 2,3-dihydro-1H-isoindolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3,4,5-tetrahydro-1H-2-benzazepinyl, 2,3,4,5-tetrahydro-1H-3-benzazepinyl, 1,2,3,4,5,6-hexahydro-1-benzazocinyl, 1,2,3,4,5,6-hexahydro-2-benzazocinyl, 1,2,3,4,5,6-hexahydro-3-benzazocinyl, 2,3,4,5,6,7-hexahydro-1H-1-benzazonyl, 2,3,4,5,6,7-hexahydro-1H-2-benzazonyl, 2,3,4,5,6,7-hexahydro-1H-3-benzazonyl, 2,3,4,5,6,7-hexahydro-1H-4-benzazonyl, β-carbolynyl, phenothiadinyl, 3H-3-benzazepinyl, 3,4-dihydroquinolyl, benzimidanyl, 1,4-benzodiazepinyl or 10,11-dihydro-5H-dibenz (b,f) azepine-5-yl.

Claim 11

The peptide as claimed in claim 9 wherein the ring formed by R₈ and R₉ is a hexamethyleneiminyl, 10,11-dihydro-5H-dibenz (b,f) azepin-5-yl, morpholinyl, piperidinyl, methylpiperazinyl or 1-(2-pyrimidyl) piperazinyl.

Claim 12

The peptide as claimed in claim 2 wherein the C₆₋₁₅ aromatic hydrocarbon group is a phenyl or napthyl group.

Claim 13

The peptide as claimed in claim 2 wherein the 5- or 6- membered heterocyclic group which contains 1 to 4 hetero atoms of O,S and N or the group as condensed with another aromatic ring is a 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, thiazol-4-yl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyranyl, indol-3-yl, N-methylindol-3-yl, 2-quinolyl or quinoxalin-2-yl.

Claim 14

The peptide as claimed in claim 1 wherein R₁ is a straight or branched C₁₋₁₀ alkyl, C₃₋₁₀ cycloalkyl, C₁₋₈ alkoxy, phenyl, napthyl, phenyl-C₁₋₁₀ alkyl, indan-1-yl, indan-2-yl, 1,2,3,4-tetrahydronaphthalene-1-yl, 1,2,3,4-tetrahydronaphthalene-2-yl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, thiazol-4-yl, 2-pyridyl, 4-pyridyl, 2-pyranyl, indol-3-yl, N-methylindol-3-yl, 2-quinolyl, quinoxalin-2-yl, mono- or di-phenylamino, phenyl-C₁₋₁₀ alkyl amino, methylpiperazino or 1-(2-pyrimidyl)piperazino.

Claim 15

The peptide as claimed in claim 1 wherein R₂ is a hydrogen atom or a straight or branched C₁₋₆ alkyl group.

Claim 16

The peptide as claimed in claim 1 wherein R₂ is a hydrogen atom.

Claim 17

The peptide as claimed in claim 1 wherein R₃ is a C₁₋₈ alkyl, C₃₋₈ cycloalkyl or C₃₋₈ cycloalkyl-C₁₋₈ alkyl group wherein a methylene (-CH₂-) of the group may be interrupted by an oxygen atom or a sulfur atom.

Claim 18

The peptide as claimed in claim 17 wherein the C₁₋₈ alkyl group wherein a methylene (-CH₂-) of the group interrupted by an oxygen atom or a sulfur atom is a methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, methylthiomethyl, ethylthiomethyl, 2-methylthioethyl, 2-ethylthioethyl, 3-methylthiopropyl or 3-ethylthiopropyl group.

Claim 19

The peptide as claimed in claim 17 wherein the C₃₋₈ cycloalkyl group wherein a methylene (-CH₂-) of the group interrupted by an oxygen atom or a sulfur atom is a tetrahydrofuran-2-yl or tetrahydrothiophen-2-yl group.

Claim 20

The peptide as claimed in claim 17 wherein the C₃₋₈ cycloalkyl-C₁₋₈ alkyl group wherein a methylene (-CH₂-) of the group interrupted by an Oxygen atom or a sulfur atom is a cyclopenthlthiomethyl or cyclohexylthiomethyl group.

Claim 21

The peptide as claimed in claim 1 wherein R₃ is a C₁₋₆ alkyl group.

Claim 22

The peptide as claimed in claim 1 wherein R₄ is a heterocyclic-substituted C₁₋₆ alkyl group which may be substituted wherein the heterocycle is a 5- or 6-heterocyclic group having 1 to 4 hetero atoms of O,S and N or the group as condensed with another ring.

Claim 23

The peptide as claimed in claim 22 wherein the carbon atom of the heterocyclic-substituted C₁₋₆ alkyl group may be substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl group, a halogen atom, a hydroxyl group, a carboxyl group, a C₁₋₆ alkoxy group and a C₁₋₆ alkylcarbonyl group, and the nitrogen atom of the heterocyclic-substituted C₁₋₆ alkyl group may be substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl group, a C₁₋₆ alkylcarbonyl group and a hydroxy-C₁₋₆ alkyl group.

Claim 24

The peptide as claimed in claim 1 wherein R₄ is a 2-pyridyl-C₁₋₆ alkyl, imidazol-2-yl-C₁₋₆ alkyl, imidazol-4-yl-C₁₋₆ alkyl, indol-3-yl-C₁₋₆ alkyl, N-methylindol-3-yl-C₁₋₆ alkyl, N-ethylindol-3-yl-C₁₋₆ alkyl, N-hydroxymethylindol-3-yl-C₁₋₆ alkyl, N-formylindol-3-yl-C₁₋₆ alkyl, thiazol-4-yl-C₁₋₆ alkyl or 5-fluoroindol-3-yl-C₁₋₆ alkyl group.

Claim 25

The peptide as claimed in claim 1 wherein R₄ is a indol-3-yl-C₁₋₆ alkyl or N-methylindol-3-yl-C₁₋₆ alkyl group.

Claim 26

The peptide as claimed in claim 1 wherein R₅ is a hydrogen atom or a C₁₋₆ alkyl group.

Claim 27

The peptide as claimed in claim 1 wherein R₅ is a hydrogen atom.

Claim 28

The peptide as claimed in claim 1 wherein R₆ is a hydrogen atom, a straight or branched C₁₋₆ alkyl group which may be substituted, a C₆₋₁₂ aromatic hydrocarbon group which may be substituted or a 5- or 6- membered aromatic heterocyclic group which contains 1 to 4 hetero atoms of O,S and N or the group as condensed with another ring which may be substituted.

Claim 29

The peptide as claimed in claim 28 wherein the straight or branched C₁₋₆ alkyl group may be substituted by 1 to 3 substituents selected from the group consisting of (i) a C₆₋₁₅ aromatic hydrocarbon group, (ii) a 5- to 6- membered aromatic heterocyclic group which contains 1 to 4 hetero atoms of O, S and N or the group as condensed with another aromatic ring, (iii) a sulfur-containing group selected from the group consisting of a thione, mercapto, methylthio, ethylthio and phenylthio, (iv) a oxygen-containing group selected from the group consisting of a ketone, hydroxy, methoxy, ethoxy, phenoxy and benzyloxy and (v) a nitrogen-containing group selected from the group consisting of an amino, N-methylamino, N-ethylamino and guanidino.

Claim 30

The peptide as claimed in claim 28 wherein the C₆₋₁₂ aromatic hydrocarbon group may be substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl group, a halogen atom, a C₁₋₆ alkoxy group, a C₁₋₆ alkylthio group, a C₁₋₆ alkylcarbonyl group and a C₁₋₆ alkoxycarbonyl group.

Claim 31

The peptide as claimed in claim 30 wherein the C₆₋₁₂ aromatic hydrocarbon group is a phenyl, 1-naphthyl or 2-naphtyl.

Claim 32

The peptide as claimed in claim 28 wherein the 5- or 6- membered aromatic heterocyclic group which contains 1 to 4 hetero atoms of O, S and N or the group as condensed with another ring may be substituted by 1 to 3 substituents selected from the group consisting of a C₁₋₆ alkyl group, a halogen atom, a C₁₋₆ alkoxy group, a C₁₋₆ alkylthio group, a C₁₋₆ alkylcarbonyl group and a C₁₋₆ alkoxycarbonyl group.

Claim 33

The peptide as claimed in claim 32 wherein the 5- or 6- membered aromatic heterocyclic group which contains 1 to 4 hetero atoms of O, S and N or the group as condensed with another ring is a furyl, thienyl, pyridyl, thiazolyl, imidazolyl or indolyl.

Claim 34

The peptide as claimed in claim 1 wherein R₆ is a C₁₋₆ alkyl, furyl, thienyl, pyridyl, pyridyl-C₁₋₆ alkyl or indolyl-C₁₋₆ alkyl group.

Claim 35

The peptide as claimed in claim 1 wherein X is (i) a group resulting from elimination of one hydrogen atom from the α-amino group of α-amino acid having at least one aromatic cyclic group or (ii) an alkylamino group substituted by an aromatic cyclic group.

Claim 36

The peptide as, claimed in claim 35 wherein the aromatic cyclic group is (i) a C₆₋₁₅ aromatic hydrocarbon group which may be substituted or (ii) a 5- or 6- membered aromatic heterocyclic group having 1 to 4 hetro atoms of O, S and N or the group as condensed with another aromatic ring which may be substituted.

Claim 37

The peptide as claimed in claim 36 wherein the C₆₋₁₅ aromatic hydrocarbon group may be substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxy group, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, a carboxyl group, a C₁₋₆ alkylcarbonyl group and a C₁₋₆ alkoxycarbonyl group.

Claim 38

The peptide as claimed in claim 36 wherein the 5- or 6- membered aromatic heterocyclic group having 1 to 4 hetero atoms of O, S, N or the group as condensed with another aromatic ring may be substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxy group, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, a carboxyl group, a C₁₋₆ alkylcarbonyl group and a C₁₋₆ alkoxycarbonyl group.

Claim 39

The peptide as claimed in claim 36 wherein the C₆₋₁₅ aromatic hydrocarbon group is a phenyl or α-naphtyl group.

Claim 40

The peptide as claimed in claim 36 wherein the 5- or 6- membered aromatic heterocyclic group having 1 to 4 hetero atoms of O,S and N or the group as condensed with other aromatic rings is a 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, thiazol-4-yl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyranyl, indol-3-yl, N-methylindol-3-yl, 2-quinolyl or quinoxalin-2-yl group.

Claim 41

The peptide as claimed in claim 35 wherein the α-amino acid may be substituted or protected at a 1-carboxyl group thereof by an ester or an amide.

Claim 42

The peptide as claimed in claim 35 wherein the α-amino acid is Gly, Ala, Val, Leu, Ile, Ser, Thr, Glu, Asn, Phe, Trp, Met, His, Cys, Arg, Asn, Gln, Tyr, (I)Tyr, diiodo-Tyr, Phg, Cha, Nva, NIe, Rya(2), Pya(3) or Thi which may be substituted or protected at a 1-carboxyl group thereof by (i) an ester selected from the group consisting of a benzyl ester, diphenylmethyl ester and trityl ester or (ii) an amide selected from the group consisting of a phenylamide, benzylamide, diphenylamide, dibenzylamide, 2-phenylethylamide, 2,2-diphenylethylamide, 1,2-diphenylethylamide and indol-3-yl-methylamide.

Claim 43

The peptide as claimed in claim 35 wherein the group resulting from elimination of one hydrogen atom from the α-amino group of α-amino acid having at least one aromatic cyclic group is a group selected from the group consisting of Phe-OH, -Tyr-OH, -Trp-OH, -Phg-OH, -(m-F)Tyr-OH, -(p-F)Phe-OH, -(p-Cl)Phe-OH, -(p-Me)Phe-OH, -Trp(Me)-OH, - Trp(CHO)-OH, -Phe-Trp-OH, -Trp-Phe-OH,-Tyr-Trp-OH, -Trp-Phe-OH, -(m-F)Tyr-(p-F)Phe-OH, -Glu(OBzl)-OH, -Glu-OBzl, - Asp(OBzl)-OH, -Asp-OBzl, -Asp-Asp(OBzl)-OH, -Glu(NBzl₂)-OH, -Glu(NHBzl)-OH, -Asp(NBzl₂)-OH, -Asp(NHBzl)-OH, -Glu-NBzl₂, -Glu-NHBzl, -Asp-NBzl₂, -Asp-NHBzl, -Glu-NHCHPhCH₂Ph, -Asp-NHCHPhCH₂Ph, -Glu-NHCH₂CHPh₂, -Asp-NHCH₂CHPh₂, -Glu(NHCHPhCH₂Ph)-OH, -Asp(NHCHPhCH₂Ph)-OH -Glu(NHCH₂CHPh₂)-OH, -Asp(NHCH₂CHPh₂)-OH, -Glu(NHCH₂CH₂-Ind)-OH, -Asp(NHCH₂CH₂-Ind)-OH, -Glu-NHCH₂CH₂-Ind, -Asp-NHCH₂CH₂-Ind, -Trp-NH-Ind(OH), -Tyr-Iqu(OH), -(I)Tyr-Phe-OH, -Trp-Trp-OH, -Tyr(Bzl)-Phe-OH, -Tyr(Bzl)-Trp-OH, -(I)Tyr-Trp-OH, -(I)Tyr-Tyr-OH, -Trp-His-OH, -His-Trp-OH, -Tyr-His-OH, -His-Tyr-OH, -Phe-His-OH, -His-Phe-OH, -Phe-Trp-OH, -Phe-Tyr-OH and -Phe-Phe-OH.

Claim 44

The peptide as claimed in claim 35 wherein the alkylamino group is a C₁₋₁₀ alkyl amino group or a C₃₋₁₀ cycloalkyl amino group.

Claim 45

The peptide as claimed in claim 35 wherein the alkylamino group substituted by an aromatic cyclic group is a group selected from the group consisting of -NBzl₂, -NHBzl, -NHCHPhCH₂Ph, -NHCH₂CHPh₂ and -NHCH₂CH₂-Ind.

Claim 46

The peptide as claimed in claim 1 wherein X is a group selected from the group consisting of -Tyr-OH, -Phe-OH, -Trp-OH, -Phg-OH, -Tyr-Phe-OH, -Tyr-Trp-OH, -Trp-Trp-OH, -(m-F)Tyr-OH, -(P-F)Phe-OH, -(m-F)Tyr-(p-F)Phe-OH, -(I)Tyr-Phe-OH, -Tyr(Bzl)-Phe-OH, -Trp(Bzl)-Trp-OH, -(I)Tyr-Trp-OH, -(I)Tyr-Tyr-OH, -Glu(Obzl)-OH, -Glu-OBzl, -Asp(OBzl)-OH, -Asp-Obzl, -Glu-NHCHPhCH₂Ph, -Glu-NHCH₂CHPh₂, -Asp-NHCHPhCH₂Ph, -Asp-NHCH₂CHPh₂, -Asp-NHCH₂CH₂-Ind, -Asp-(NHCH₂CH₂-Ind)-OH, -Glu-Asp-NHCH₂CH₂-Ind, -Glu-Asp(NHCH₂CH₂-Ind)-NBzl₂, -Asp-NBzl₂, -Trp-NH-Ind and -Trp-Iqu.

Claim 47

The peptide as claimed in claim 1 wherein n is 0 or an integer of 1 to 4.

Claim 48

The peptide as claimed in claim 1 wherein n is 0.

Claim 49

The peptide as claimed in claim 1 wherein n is 0 and the -N(R₅)-(HCR₆)-(CH₂)n-CO- moiety is an α-amio acid residue selected from the group consisting of Ala, Val, Leu, Ile, Trp, Pya(2) and Pya(3).

Claim 50

The peptide as claimed in claim 1 wherein m is an integer of 2 to 6.

Claim 51

The peptide as claimed in claim 1 wherein n is 2, 3 or 5.

Claim 52

The peptide as claimed in claim 1 wherein R₁ is a hexamethyleneimino group, R₂ is a hydrogen atom, R₃ is a C₁₋₆ alkyl group, R₄ is a indol-3-yl-C₁₋₆ alkyl group, R₅ is a hydrogen atom, R₆ is a C₁₋₆ alkyl group or a 5- or 6- membered aromatic heterocyclic group having 1 to 4 hetero atoms of O, S and N, m is 2, n is 0 and X is -Tyr-(D)Phe-OH, -Tyr(I)-(D)Phe-OH or -Trp-NH-Ind-OH.

Claim 53

The peptide as claimed in claim 1 wherein R₁ is a hexamethyleneimino group, R₂ is a hydrogen atom, R₃ is a C₁₋₆ alkyl group, R₄ is a indol-3-yl-C₁₋₆ alkyl group, R₅ is a hydrogen atom, R₆ is a C₁₋₆ alkyl group, m is 2, n is 0 and X is -Tyr-(D)Phe-OH.

Claim 54

Hexamethyleneimino-CO-Leu-(D)Trp-(D)Ala-βAla-Tyr-(D)Phe-OH, or a pharmaceutically acceptable salt thereof.

Claim 55

Hexamethyleneimino-CO-Leu-(D)Trp-(D)Ala-βAla-Tyr(I)-(D)Phe-OH, or a pharmaceutically acceptable salt thereof.

Claim 56

Hexamethyleneimino-CO-Leu-(D)Trp-(D)Ala-βAla-Trp-NH-Ind-OH, or a pharmaceutically acceptable salt thereof.

Claim 57

Hexamethyleneimino-CO-Leu-(D)Trp-(D)Ala-βAla-Tyr-(D)Phe-OH.

Claim 58

A method of producing the peptide of claim 1 wherein a partial peptide or amino acids capable of constituting the peptide represented by the formula of claim 1 are condensed with the remaining moiety, and when the product has a protected group, it is deprotected.

Claim 59

A pharmaceutical composition containing the peptide of one of claims 1-57 or a pharmacologically acceptable salt thereof.

Claim 60

The pharmaceutical composition of claim 59 which is an endothelin receptor antagonist.

Claim 61

Use of the peptide or a pharmaceutically acceptable salt thereof as claimed in one of claims 1-57 for preparing an endothelin receptor antagonist.