Claims
- 1. A compound of Formula (I): ##STR41## wherein (Z) is ##STR42## P is tetrazol-5-yl, XO.sub.2 R.sub.6 or C(O)N(R.sub.6)S(O).sub.1 R.sub.10 ;
- R.sup.a is independently hydrogen or C.sub.1-6 alkyl;
- R.sub.1 is independently hydrogen, Ar or C.sub.1-6 alkyl;
- R.sub.2 is Ar, C.sub.1-8 alkyl, C(O)R.sub.14 or ##STR43## R.sub.3 and R.sub.5 are independently R.sub.13 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.13 CO.sub.2 R.sub.7, --X--R.sub.9 --Y or --X(CH.sub.2).sub.11 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 independently R.sub.11, OH, C.sub.1-5 alkoxy, S(O).sub.q R.sub.11, N(R.sub.6).sub.2, 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.1-8 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.1-10 alkyl; or R.sub.7 is (CH.sub.2).sub.n Ar;
- R.sub.8 is independently 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, tetrazole or OR.sub.6 ;
- R.sub.9 is independently a bond, C.sub.1-10 alkylene, C.sub.1-10 alkenylene, C.sub.1-10 alkylidene, C.sub.1-10 alkynylene, all of which may be linear or branched, or phenylene, all of which may be unsubstituted or substituted by one or more OH, N(R.sub.6).sub.2, COOH or halogen;
- R.sub.10 is independently C.sub.1-10 alkyl, N(R.sub.6).sub.2 or Ar;
- R.sub.11 is independently hydrogen, Ar, C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, 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 independently hydrogen, C.sub.1-6 alkyl, C.sub.2 6 alkenyl or C.sub.2 7 alkynyl;
- R.sub.13 is independently divalent Ar, C.sub.1-10 alkylene, C.sub.1-10 alkylidene, C.sub.2-10 alkenylene, 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.14 is independently hydrogen, C.sub.1-10 alkyl, XC.sub.1-10 alkyl, Ar or XAr;
- R.sub.15 is independently hydrogen, Ar, C.sub.1-6 alkyl, or XAr;
- R.sub.16 is independently C.sub.1-6 alkyl or phenyl substituted by one or more C.sub.1-6 alkyl, OH, C.sub.1-5 alkoxy, S(O).sub.q R.sub.6, N(R.sub.6).sub.2, Br, F, I, Cl, CF.sub.3 or NHCOR.sub.6 ;
- X is independently (CH.sub.2).sub.n, O, NR.sub.6 or S(O).sub.q ;
- Y is independently CH.sub.3 or X(CH.sub.2).sub.n Ar;
- Ar is: ##STR44## naphthyl, all of which may be unsubstituted or substituted by one or more Z.sub.1 or Z.sub.2 groups;
- A is independently C.tbd.O, or (C(R.sub.6).sub.2).sub.m ;
- D is independently --CH.sub.2 -- or --O--;
- Z.sub.1 and Z.sub.2 are independently hydrogen, XR.sub.6, C.sub.1-8 alkyl, (CH.sub.2).sub.q CO.sub.2 R.sub.6, C(O)N(R.sub.6).sub.2, CN, (CH.sub.2).sub.n OH, NO.sub.2, F, Cl, Br, I, N(R.sub.6).sub.2, NHC(O)R.sub.6, O(CH.sub.2).sub.m C(O)NR.sub.1 SO.sub.2 R.sub.15, (CH.sub.2).sub.m OC(O)NR.sub.a SO.sub.2 R.sub.16, O(CH.sub.2).sub.m NR.sub.a C(O)NR.sub.a SO.sub.2 R.sub.16, NR.sub.7 C(O)NR.sub.7 SO.sub.2 R.sub.11, or tetrazolyl which may be substituted or unsubstituted by C.sub.1-6 alkyl, CF.sub.3 or C(O)R.sub.6 ;
- Ar' is independently naphthyl, indolyl, faryl, oxazolyl, pyridyl thienyl, oxazolidinyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolyl, imidazolidinyl, thiazolidinyl, isoxazolyl, oxadiazolyl, thiadiazolyl, morpholinyl, piperidinyl, piperazinyl, pyrrolyl, or pyridyl; all of which may be unsubstituted or substituted by one or more XR.sub.9 --Y, X(CH.sub.2).sub.n R.sub.8, Z.sub.1 or Z.sub.2 groups;
- m is independently 1 to 3;
- n is independently 0 to 6;
- q is independently 0, 1 or 2;
- provided R.sub.3, R.sub.4 and R.sub.5 arc not O--O(CH.sub.2).sub.n Ar;
- 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 treatment of diseases caused by an excess of endothelin comprising administering to a subject in need thereof, an effective amount of an endothelin receptor antagonist of claim 1.
- 4. A method of treating renal failure, hypertension, pulmonary hypertension or heart failure which comprises administering to a subject in need thereof, an effective amount of a compound of claim 1.
- 5. A compound of claim 1 selected from the group consisting of:
- (E)-alpha-[[5-Butyl-4-[4-[(2-carboxyphenyl)methoxy]-2-methoxypyrid-5-yl]-pyrrol-3-yl]methylene]-6-methoxy-1,3-benzodioxole-5-propanoic acid; or
- (E)-alpha-[[1-Butyl-2-[4-[(2-carboxyphenyl)methoxy]-2-methoxypyrid-5-yl]-pyrrol-3-yl]methylene]-6-methoxy-1,3-benzodioxole-5-propanoic acid.
Parent Case Info
This application is a divisional of Ser. No. 09/142,510 filed Jul. 31, 1998 now U.S. Pat. No. 6,022,886 which claims the benefit of provision application Ser. No. 60/010,984 filed Feb. 1, 1996 and which is also a 371 of PCT/US97/00954 filed Jan. 31, 1997.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
3063978 |
Lynn et al. |
Nov 1962 |
|
3678063 |
Binon et al. |
Jul 1972 |
|
Divisions (1)
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Number |
Date |
Country |
Parent |
142510 |
Jul 1998 |
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