Claims
- 1. A compound of Formula (I): ##STR13## wherein: R.sub.1 is --X(CH.sub.2).sub.n R.sub.8 ;
- R.sub.2 is hydrogen, Ar or C.sub.1-4 alkyl;
- P.sub.1 is tetrazole, SO.sub.2 NR.sub.7 R.sub.11, CONR.sub.7 SO.sub.2 R.sub.11, (CH.sub.2).sub.5 CO.sub.2 R.sub.7 ;
- R.sub.3 and R.sub.5 are independently hydrogen, R.sub.11, OH, C.sub.1-8 alkoxy, S(O).sub.q R.sub.11, N(R.sub.6).sub.2, Br, F, I, Cl, CF.sub.3, NHCOR.sub.6, R.sub.11 CO.sub.2 R.sub.7, --X--R.sub.9 --Y, or --X(CH.sub.2).sub.n R.sub.8 wherein each methylene group within --X(CH.sub.2).sub.n R.sub.8 may be unsubstituted or substituted by one or two --(CH.sub.2).sub.n Ar groups;
- R.sub.4 is hydrogen, R.sub.11, OH, C.sub.1-5 alkoxy, S(O).sub.q R.sub.11, N(R.sub.6).sub.2, --X(R.sub.11), Br, F, I, Cl or NHCOR.sub.6 wherein the C.sub.1-5 alkoxy may be unsubstituted or substituted by OH, methoxy or halogen;
- R.sub.6 is independently hydrogen or C.sub.1-4 alkyl;
- R.sub.7 is independently hydrogen, C.sub.1-10 alkyl, C.sub.2-10 alkenyl or C.sub.2-8 alkynyl, all of which may be unsubstituted or substituted by one or more OH, N(R.sub.6).sub.2, CO.sub.2 R.sub.12, halogen or XC.sub.1-5 alkyl; or R.sub.7 is (CH.sub.2).sub.n Ar;
- R.sub.8 is hydrogen, R.sub.11, CO.sub.2 R.sub.7, CO.sub.2 C(R.sub.11).sub.2 O(CO)XR.sub.7, PO.sub.3 (R.sub.7).sub.2, SO.sub.2 NR.sub.7 R.sub.11, NR.sub.7 SO.sub.2 R.sub.11, CONR.sub.7 SO.sub.2 R.sub.11, SO.sub.3 R.sub.7, SO.sub.2 R.sub.7, P(O)(OR.sub.7)R.sub.7, CN, --CO.sub.2 (CH.sub.2).sub.m C(O)N(R.sub.6).sub.2, C(R.sub.11).sub.2 N(R.sub.7).sub.2, C(O)N(R.sub.6).sub.2 or tetrazole;
- R.sub.9 is (CH.sub.2).sub.n, C.sub.1-10 alkylene, C.sub.2-10 alkenylene or phenylenyl, all of which may be unsubstituted or substituted by one or more OH, N(R.sub.6).sub.2, COOH, halogen, or R.sub.9 may be <C.dbd.O or XC.sub.1-5 alkyl;
- R.sub.11 is hydrogen, Ar, C.sub.1-8 alkylene, C.sub.2-8 alkenylene, C.sub.2-8 alkynylene, all of which may be unsubstituted or substituted by one or more OH, CH.sub.2 OH, N(R.sub.6).sub.2 or halogen;
- R.sub.12 is hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-7 alkynyl;
- X is (CH.sub.2).sub.n, O or NR.sub.6 ;
- Y is CH.sub.3 or X(CH.sub.2).sub.n Ar;
- Ar is: ##STR14## naphthyl, indolyl, pyridyl, thienyl, oxazolidinyl, oxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolyl, imidazolidinyl, thiazolidinyl, isoxazolyl, oxadiazolyl, thiadiazolyl, morpholinyl, piperidinyl, piperazinyl, pyrrolyl, or pyrimidyl; all of which may be unsubstituted or substituted by one or more R.sub.3 or R.sub.4 groups;
- A is C.dbd.O, or (C(R.sub.6).sub.2).sub.m ;
- B is --CH.sub.2 -- or --O--;
- Z.sub.1 and Z.sub.2 are independently hydrogen, C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, OH, C.sub.1-8 alkoxy, S(O)qC.sub.1-8 alkyl, N(R.sub.6).sub.2, Br, F, I, Cl, NHCOR.sub.6, --X--R.sub.9 --Y, --X(CH.sub.2).sub.n R.sub.8, phenyl, benzyl or C.sub.3-6 cycloalkyl wherein the C.sub.1-8 alkyl, C.sub.2-8 alkenyl or C.sub.2-8 alkynyl may be optionally substituted by COOH, OH, CO(CH.sub.2).sub.n CH.sub.3, CO(CH.sub.2).sub.n CH.sub.2 N(R.sub.6).sub.2, or halogen; or Z.sub.1 and Z.sub.2 together may be --O--A--O-- on contiguous carbons;
- Z.sub.3 is Z.sub.1 or --X--R.sub.9 ----Y;
- q is zero, one or two;
- n is an integer from 0 to six;
- s is an integer from one to six;
- m is 1, 2 or 3;and the dotted line indicates the optional presence of a double bond;
- or a pharmaceutically acceptable salt thereof.
- 2. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
- 3. A method of antagonizing endothelin receptors which comprises administering to a subject in need thereof, an effective amount to antagonize endothelin receptors of a compound of claim 1.
- 4. A method of treating hypertension which comprises administering to a subject in need thereof an effective amount of a compound of claim 1.
- 5. A method of treating renal failure which comprises administering to a subject in need thereof, an effective amount of a compound of claim 1.
- 6. A method of treating cerebrovascular disease which comprises administering to a subject in need thereof, an effective amount of a compound of claim 1.
Parent Case Info
This is a divisional of application Ser. No. 08/464,761, filed Dec. 12, 1996, now U.S. Pat. No. 5,736,564 which is a 371 of International Application No. PCT/US95/07193 filed Jun. 6, 1995; which claims priority to U.S. Ser. No. 08/262,801, filed Jun. 20, 1994, now abandoned.
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Divisions (1)
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