Methods of treating hormone-related conditions using thio-oxindole derivatives
The present invention provides methods of inducing contraception which includes delivering to a female a composition containing a compound of formula I, or tautomers thereof, in a regimen which involves delivering one or more of a selective estrogen receptor modulator, wherein formula I is: and wherein R 1 -R 5 and Q 1 are defined as described herein. Methods of providing hormone replacement therapy and for treating carcinomas, dysfunctional bleeding, uterine leiomyomata, endometriosis, and polycystic ovary syndrome is provided which includes delivering a compound of formula I and a selective estrogen receptor modulator are also described.
1. A method of inducing contraception comprising delivering to a female of child-bearing age a composition comprising a compound of formula I in a regimen which involves delivering a pharmaceutically effective amount of one or more selective estrogen receptor modulator selected from the group consisting of EM-800, EM-652, raloxifene hydrochloride, arzoxifene, lasofoxifene, droloxifene, tamoxifen citrate, 4-hydroxytamoxifen citrate, clomiphene citrate, toremifene citrate, pipendoxifene, idoxifene, levormeloxifene, centchroman, nafoxidene, and bazedoxifene to said female, wherein formula I is:
wherein:
R 1 and R 2 are joined to form —CH 2 (CH 2 ) n CH 2 —;
n is 3 or 4;
R 3 is H;
R 4 is H;
R 5 is a five membered heterocyclic ring having 1 NR 6 heteroatom and having one CN and one substituent selected from the group consisting of H, halogen, C 1 to C 3 alkyl, and CSR D ;
R D is NH 2 ;
R 6 is H or C 1 to C 3 alkyl;
Q 1 is S;
or a pharmaceutically acceptable salt, tautomer, metabolite, or prodrug thereof.
2. The method according to claim 1 , wherein said compound of formula I and said selective estrogen receptor modulator are delivered in a single composition.
3. The method according to claim 1 , wherein said compound of formula I and said selective estrogen receptor modulator are delivered separately.
4. The method according to claim 1 , wherein said compound is delivered at a daily dosage of about 0.1 to about 50 mg.
5. The method according to claim 1 , wherein said regimen comprises delivering said composition daily for 1 to about 21 days, wherein said regimen is a cycle which is repeated monthly.
6. The method according to claim 1 , wherein said selective estrogen receptor modulator is delivered at a daily dosage of about 0.2 to about 100 mg.