Claims for Patent: 7,176,211

Summary for Patent: 7,176,211

Title:	Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
Abstract:	GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.
Inventor(s):	Zhiqiang Guo, Yongsheng Chen, Dongpei Wu, Chen Chen, Warren Wade, Wesley J. Dwight, Charles Q. Huang, Fabio C. Tucci
Assignee:	Neurocrine Biosciences Inc
Application Number:	US11/251,085
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,176,211
Patent Claims:	1. A method for treating a condition selected from the group of prostate cancer, benign prostatic hypertrophy, breast cancer and endometriosis in a subject in need thereof comprising administering to the subject a pharmaceutically effective amount of a compound represented by the following structure: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein: R1a, R1b and R1c are the same or different and independently hydrogen, halogen, C1-4alkyl, hydroxy or alkoxy, or R1a and R1b taken together form —OCH2O— or —OCH2CH2—; R2a and R2b are the same or different and independently hydrogen, halogen, trifluoromethyl, cyano or —SO2CH3; R3 is hydrogen or methyl; R4 is phenyl or C3-7alkyl; R5 is hydrogen or C1-4alkyl; R6 is -COOH or an acid isostere; and X is C1-6alkanediyl optionally substituted with from 1 to 3 C1-6alkyl groups. 2. A method according to claim 1, wherein X is a straight chain C1-6alkanediyl. 3. A method according to claim 2, wherein R6 is —COOH. 4. A method according to claim 3, wherein R4 is phenyl. 5. A method according to claim 4, wherein R1a is halogen and R1b is alkoxy. 6. A method according to claim 4, wherein R3 is methyl. 7. A method according to claim 4, wherein the condition is endometriosis. 8. A method according to claim 4, wherein the condition is benign prostatic hypertrophy. 9. A method according to claim 4, wherein the condition is prostate cancer. 10. A method according to claim 4, wherein the condition is breast cancer. 11. A method according to claim 1, wherein the compound is 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione, 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(3-isopropylphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione, 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-(cyclohexyl)ethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione, or 3-[2(R)-{2-[1-(5-tetrazoyl)propyl]-amino}-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylsulfonylbenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione. 12. A method according to claim 11, wherein the condition is endometriosis. 13. A method according to claim 11, wherein the condition is benign prostatic hypertrophy. 14. A method according to claim 11, wherein the condition is prostate cancer. 15. A method according to claim 11, wherein the condition is breast cancer. 16. A method according to claim 1, wherein the compound is 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-chlorophenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-pyrimidine-2,4(1H,3H)-dione, 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-pyrimidine-2,4(1H,3H)-dione, 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-chloro-3-methylphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-pyrimidine-2,4(1H,3H)-dione, 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-chlorophenyl)-1-[2-fluoro-6-(methylsulfonyl)benzyl]-pyrimidine-2,4(1H,3H)-dione, 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-pyrimidine-2,4(1H,3H)-dione, or 3-[2(R)-{hydroxycarbonylpropyl-amino}-2-(isobutyl)ethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-pyrimidine-2,4(1H,3H)-dione. 17. A method according to claim 16, wherein the condition is endometriosis. 18. A method according to claim 16, wherein the condition is benign prostatic hypertrophy. 19. A method according to claim 16, wherein the condition is prostate cancer. 20. A method according to claim 16, wherein the condition is breast cancer.