Amino acid derivatives, the preparation and use thereof as endothelin antagonists

A compound of formula I

• where R is tetrazolyl, cyano or a radical
• where R1 has the following meanings:
• b) succinimidyl;
• d) a radical
• where k is 0, 1 or 2, p is 1, 2, 3 or 4, and R9 is C1-C4-alkyl, C3-C7-cycloalkyl, C3-C6-alkenyl, C3-C6-alkynyl or phenyl which is unsubstituted or substituted by one or more of the following radicals:
• halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, C1-C4-alkylthio, mercapto, amino, C1-C4-alkylamino and C1-C4-dialkylamino;
• e) a radical OR10, where R10 is:
• hydrogen, an alkali metal cation or an alkaline earth metal cation, ammonium or a physiologically tolerated alkylammonium ion, C3-C8-cycloalkyl;
• C1-C8-alkyl;
• benzyl which is unsubstituted or substituted by one or more of the following radicals:
• halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, mercapto, C1-C4-alkylthio, amino, C1-C4-alkylamino and C1-C4-dialkylamino;
• C3-C6-alkenyl or C3-C6-alkynyl, which is unsubstituted or carries one to five halogen atoms;
• phenyl which is unsubstituted or substituted by one to five halogen atoms and/or from one to three of the following radicals:
• nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, mercapto, C1-C4-alkylthio, amino, C1-C4-alkylamino and C1-C4-dialkylamino;
• f) a radical
• where R11 is:
• C1-C4-alkyl, C3-C6-alkenyl, C3-C6-alkynyl, C3-C8-cycloalkyl, which radicals are unsubstituted or carry a C1-C4-alkoxy, C1-C4-alkylthio and/or phenyl radical;
• phenyl which is unsubstituted or substituted by one to five halogen atoms and/or one to three of the following radicals:
• nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, mercapto, C1-C4-alkylthio, amino, C1-C4-alkylamino and C1-C4-dialkylamino;
• g) a radical
• where R12 is C1-C4-alkyl, C3-C6-alkenyl, C3-C6-alkynyl, C3-C8-cycloalkyl, which radicals are unsubstituted or carry a C1-C4-alkoxy, C1-C4-alkylthio and/or phenyl radical;
• phenyl which is unsubstituted or substituted by one to five halogen atoms and/or one to three of the following radicals:
• nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, mercapto, C1-C4-alkylthio, amino, C1-C4-alkylamino and C1-C4-dialkylamino;
• h) a radical
• where R13 and R14, independently of one another, are hydrogen, C1-C7-alkyl, C3-C7-cycloalkyl, C3-C7-alkenyl, C3-C7-alkynyl, benzyl or phenyl which are unsubstituted or substituted by one to five halogen atoms and/or one to three of the following radicals:
• nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, mercapto, C1-C4-alkylthio, amino, C1-C4-alkylamino and C1-C4-dialkylamino;
• or R13 and R14 together form a C4-C7-alkylene chain or a chain consisting of 4 to 7 methylene members and one member selected from the group of oxygen, nitrogen and sulfur, which chain is unsubstituted or substituted by C1-C4-alkyl;
• tetrazole or nitrile;
• and
• W is nitrogen;
• R2 is hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, hydroxyl, mercapto, C1-C4-alkylthio, nitro, amino, C1-C4-alkylamino or C1-C4-dialkylamino, cyano, phenyl which is unsubstituted or carries one to three of the following:
• halogen, hydroxyl, amino, mono-(C1-C3)-amino, dialkyl-(C1-C3)-amino, C1-C3-alkyl, C1-C3-alkoxy, mercapto and C1-C3-alkylthio;
• or
• X is CR15 where R15 is hydrogen or C1-C5-alkyl, C1-C5-alkoxy, C1-C5-alkylthio, nitro, phenyl, hydroxyl, mercapto, halogen, amino, C1-C4-alkylamino, C1-C4-dialkylamino or cyano, or
• R15 and R2 to form a 5- to 6-membered alkylene or alkylidene ring or a 5- or 6-membered alkylene or alkenylene ring wherein one or two carbon ring members are replaced by a nitrogen, sulfur or oxygen atom, and which ring is unsubstituted or carries one to three of the following radicals:
• halogen, nitro, cyano, hydroxyl, mercapto, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, C1-C3-alkylthio, amino, C1-C3-alkylamino and C1-C3-dialkylamino;
• or
• R15 and R3 together with the adjacent carbon atom form a 5- or 6-membered alkylene or alkylidene ring or a 5- or 6-membered alkylene or alkenylene ring wherein one or two carbon ring members are replaced by a nitrogen, sulfur or oxygen atom, and which ring is unsubstituted or carries one to three of the following radicals:
• halogen, nitro, cyano, hydroxyl, mercapto, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, C1-C3-alkylthio, amino, C1-C3-alkylamino and C1-C3-dialkylamino;
• R3 is one of the radicals given for R2,
• Y is nitrogen;
• R4 is phenyl which is unsubstituted or carries one or more of the following radicals halogen, nitro, cyano, hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, phenyl, C1-C4-alkylthio, amino, C1-C4-alkylamino and C1-C4-dialkylamino, or
• R4 and R5 are each phenyl groups which are connected to each other in the ortho positions by a direct linkage, a methylene, ethylene or ethenylene group, an oxygen or sulfur atom or an SO2, NH or N-alkyl group;
• R5 is cyclohexyl, phenyl or naphthyl which is unsubstituted or carries from one to three of the following radicals:
• halogen, nitro, cyano, hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, phenyl, C1-C4-alkylthio, amino, C1-C4-alkylamino, C1-C4-dialkylamino and two radicals on adjacent carbon atoms which form an alkylene or alkylidene group, a ring having 5 or 6 ring members selected from methylene, methylidene and oxygen;
• R6 is hydrogen, C1-C4-alkyl or C1-C4-haloalkyl
• Z is a single bond, oxygen, sulfur, sulfinyl or sulfonyl;
• R7 is hydrogen or C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl;
• Q is a single bond, a
• group
• R8 is hydrogen, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl, and R8 can furthermore be directly connected to R5 as described above, in which case R8 is a CH—R17 group where R17 is hydrogen, C1-C4-alkyl, phenyl or phenyl which is mono- to trisubstituted by methoxy, or is one of the following radicals