Prostaglandin receptor EP2 antagonists, derivatives, compositions, and uses related thereto
The present invention is directed to compounds of Formula IC: wherein the substituents are described herein. These compounds and their pharmaceutically acceptable salts thereof are prostaglandin receptor EP2 antagonists.
1. A pharmaceutical composition comprising a compound of Formula IC,
or pharmaceutically acceptable salt or prodrug thereof, wherein:
W is CH or N;
n is 1, 2, 3, or 4;
Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl;
X 1 , X 2 , X 3 , and X 4 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl;
X 5 is alkyl, wherein X 5 is optionally substituted with one or more, the same or different, halogen.
2. The composition of claim 1 , wherein n is 2.
3. A compound of Formula IC as in claim 1 , selected from the group consisting of:
N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,
3-(3,4-dimethoxyphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,
3-(3,4-dimethoxyphenyl)-N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)acrylamide,
3-(benzo[d][1,3]dioxol-5-yl)-N-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)acrylamide,
N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,
3-(3,4-dimethoxyphenyl)-N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)acrylamide,
N-(2-(5-fluoro-2-(trifluoromethyl)-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,
3-(3,4-dimethoxyphenyl)-N-(2-(5-fluoro-2-(trifluoromethyl)-1H-indol-1-yl)ethyl)acrylamide,
N-(3-(2-methyl-1H-indol-1-yl)propyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,
N-methyl-N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,
3-(4-methoxyphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)-3-(4-methoxyphenyl)acrylamide,
3-(benzo[d][1,3]dioxol-5-yl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
3-(4-ethoxy-3-methoxyphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
3-(4-isobutylphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
3-(3,4-difluorophenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
3-(3,4-difluorophenyl)-N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)acrylamide,
N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trifluorophenyl)acrylamide,
N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trifluorophenyl)acrylamide,
3-(3-bromo-4,5-dimethoxyphenyl)-N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)acrylamide,
3-(4-chloro-3-methoxyphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
3-(4-chloro-3-methoxyphenyl)-N-(2-(5-fluoro-2-methyl-1H-indol-1-yl)ethyl)acrylamide,
3-(5-bromo-2,4-dimethoxyphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
N-(2-(2-(trifluoromethyl)-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide,
3-(3,5-dimethoxyphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide,
3-(4-fluoro-3,5-dimethylphenyl)-N-(2-(2-(trifluoromethyl)-1H-indol-1-yl)ethyl)acrylamide, and
3-(4-fluoro-3,5-dimethylphenyl)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)acrylamide or salts thereof.