| abstract |
This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds that are antagonists of the progesterone receptor having the general structure: n n n wherein: R 1 , and R 2 are chosen independently from each other from H, OH; OAc; alkylaryl; alkylheteroaryl; 1-propynyl; 3-propynyl; and optionally substituted alkyl, O(alkyl); aryl; or heteroaryl groups; or R 1 and R 2 are joined to form a ring comprising —CH 2 (CH 2 ) n CH 2 — where n=0-5; —CH 2 CH 2 CMe 2 CH 2 CH 2 —; —O(CH 2 ) m CH 2 — where m=1-4; O(CH 2 ) p O— where p=1-4; —CH 2 CH 2 OCH 2 CH 2 —; —CH 2 CH 2 N(H or alkyl)CH 2 CH 2 —; n or R 1 and R 2 together comprise a double bond to CMe 2 ; C(cycloalkyl), O, or C(cycloether); n R 3 is H, OH, NH 2 , COR A ; or optionally substituted alkenyl or alkynyl groups; n R A =H or optionally substituted alkyl, alkoxy, or aminoalkyl groups; n R 4 =H, halo, CN, NH 2 , or optionally substituted alkyl, alkoxy, or aminoalkyl; n R 5 is selected from optionally substituted benzene ring; a five or six membered heterocyclic ring; a 4 or 7-substituted indole or a substituted benzothiophene; or pharmaceutically acceptable salt thereof. These methods of treatment may be used for contraception or for the treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or mininization of side effects or cyclic menstrual bleeding. Additional uses of the invention include stimulation of food intake. |