Gonadotropin-releasing hormone receptor antagonists and methods relating thereto

Patent metadata

Field	Value
Publication number	US-11713324-B2
Application number	US-202017126581-A
Country	US
Kind code	B2
Filing date	Dec 18, 2020
Priority date	Apr 6, 2007
Publication date	Aug 1, 2023
Grant date	Aug 1, 2023

Abstract

GnRH receptor antagonists are disclosed which 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, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates 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.

First claim

We claim:

1. A process for preparing 3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionic acid, comprising:
contacting a solution of 4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-N-[2-(3-hydroxy-propoxy)-phenyl]-N-methyl-benzamide with a solution of sodium periodate, followed by ruthenium (III) chloride, and
isolating the 3-(2-[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionic acid.

2. A process for preparing 4-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl}-methyl-amino}-3-methyl-phenoxy)-butyric acid comprising:
contacting a solution of 4-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-3-methyl-phenoxy)-butyric acid methyl ester in tetrahydrofuran with an aqueous solution of lithium hydroxide; and
isolating the 4-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-3-methyl-phenoxy)-butyric acid.

Assignees

• Neurocrine Biosciences Inc

Inventors

• Beaton Graham
• Chen Mi
• Coon Timothy Richard
• Ewing Todd
• Jiang Wanlong
• Moree Willy
• Rowbottom Martin
• Wade Warren
• Zhao Liren
• Lowe Richard
• Smith Nicole
• Ashweek Neil
• Zhu Yun-Fei

Classifications

• C07D495/04 Primary

  Ortho-condensed systems · CPC title

• C07C233/88

  having nitrogen atoms of carboxamide groups bound to an acyclic carbon atom and to a carbon atom of a six-membered aromatic ring wherein at least one ortho-hydrogen atom has been replaced · CPC title

• C07C235/42

  having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton · CPC title

• C07C255/57

  containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton · CPC title

• C07D213/56

  Amides · CPC title