Cyclic regimens using quinazolinone and benzoxazine derivatives

US6498154B1 · kind B1 · utility

Assignees

• Wyeth, LLC · US
• Ligand Pharmaceuticals Incorporated · US

Inventors

• Gary S. Grubb · Newtown Square, US
• Lin Zhi · San Diego, US
• Todd K. Jones · Solana Beach, US
• Puwen Zhang · Audubon, US
• James P. Edwards · San Diego, US
• Andrew Fensome · Wayne, US
• Eugene A. Terefenko · Quakertown, US
• Jay E. Wrobel · Lawrenceville, US
• Christopher M. Tegley · Thousand Oaks, US

Key dates

• Filing date: Apr 19, 2000
• Grant date: Dec 24, 2002
• Expiry date: Apr 19, 2020

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P35/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

This invention relates to cyclic combination therapies utilizing, in combination with progestins, estrogens, or both, compounds which are progesterone receptor antagonists of the general structure: wherein: R1 and R2 are H, CORA, or NRBCORA, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heterocyclic; or R1 and R2 fuse to form 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic rings; RA is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl groups; RB is H or alkyl; R3 is H, OH, NH2, CORC or alkyl, alkenyl, or alkynyl; RC is H, alkyl, aryl, alkoxy, or aminoalkyl; R4 is H, halogen, CN, NO2, alkyl, alkynyl, alkoxy, amino or aminoalkyl; R5 is benzene or 5- or 6-membered heterocyclic ring; R6 is H or alkyl; G1 is O, NR7, or CR7R8; G2 is CO or CR7R8; provided that when G1 is O, G2 is CR7R8, and G1 and G2 cannot both be CR7R8; R7 and R8 are H or an optionally substituted alkyl, aryl, or heterocyclic moiety; or pharmaceutically acceptable salt thereof. These methods may be used for contraception or treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of t…