Claims
- 1. A compound of Formula (I): ##STR10## D is S; P is CO.sub.2 R.sub.6 or C(O)N(R.sub.6)S(O).sub.q R.sub.10 ;
- R.sup.a is 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 ##STR11## 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.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 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, NR.sub.7 C(O)NR.sub.7 SO.sub.2 R.sub.11, 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 of 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 C.sub.1-6 alkyl or phenyl substituted by one or two 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 independently:
- Ar is independently: ##STR12## naphthyl, furyl, thienyl; all of which may be unsubstituted or substituted by one or more Z.sub.1 or Z.sub.2 groups;
- A is independently C.dbd.O, or (C(R.sub.6).sub.2).sub.m ;
- B 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, X(CH.sub.2).sub.n R.sub.8, O(CH.sub.2).sub.m C(O)NR.sub.a SO.sub.2 R.sub.15, (CH.sub.2).sub.m OC(O)NR.sub.a SO.sub.2 R.sub.15, or O(CH.sub.2).sub.m NR.sub.a C(O)NR.sub.a SO.sub.2 R.sub.15, or which may be substituted or unsubstituted by C.sub.1-6 alkyl, CF.sub.3 or C(O)R.sub.6 ;
- Ar' is naphthyl, furyl, thienyl; all of which may be unsubstituted or substituted by one or more XR.sub.9 --Y, 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 n is 1-6 in Formula (I) when R.sub.2 is furyl; and further provided that R.sub.3, R.sub.4 and R.sub.5 are not O--O(CH.sub.2).sub.n Ar;
- or a pharmaceutically acceptable salt thereof.
- 2. A compound of claim 1 chosen from the group consisting of:
- E-3-[4-n-Butyl-3-[(7-carboxy-4-methoxy)naphthyl]thien-2-yl]-2-[(2-methoxy-4,5-methylenedioxyphenyl)methyl]-2-propenoic acid.
- 3. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
- 4. 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.
- 5. 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.
Parent Case Info
This application is a 371 of PCT/US 97/00953 filed Jan. 31, 1997, which claims benefit of Provisional application No. 60/010,945 filed Feb. 1, 1996.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US97/00953 |
1/31/1997 |
|
|
7/31/1998 |
7/31/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/28159 |
8/7/1997 |
|
|
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5247098 |
Kumagai et al. |
Sep 1993 |
|