21-substituted progesterone derivatives as new antiprogestational agents
A compound having the general formula: in which: R 1 is a member selected from the group consisting of —OCH 3 , —SCH 3 , —N(CH 3 ) 2 , —NHCH 3 , —CHO, —COCH 3 and —CHOHCH 3 ; R 2 is a member selected from the group consisting of halogen, alkyl, acyl, hydroxy, alkoxy, acyloxy, alkyl carbonate, cypionyloxy, S-alkyl and S-acyl; R 3 is a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; R 4 is a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of ═O and ═N—OR 5 , wherein R 5 is a member selected from the group consisting of hydrogen and alkyl. In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce labor; and for contraception.
1. A compound having the formula
in which:
R 1 is a member selected from the group consisting of —OCH 3 , —SCH 3 , —N(CH 3 ) 2 , —NHCH 3 , —CHO, —COCH 3 and —CHOHCH 3 ;
R 2 is a member selected from the group consisting of halogen, alkyl, acyl, hydroxy, alkoxy, acyloxy, alkylcarbonate, cypionyloxy, S-alkyl and S-acyl;
R 3 is a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy;
R 4 is a member selected from the group consisting of hydrogen and alkyl; and
X is a member selected from the group consisting of ═O and ═N—OR 5 , wherein R 5 is a member selected from the group consisting of hydrogen and alkyl.
2. A compound in accordance with claim 1 in which:
R 1 is —N(CH 3 ) 2 .
3. A compound in accordance with claim 1 in which:
R 2 is halogen.
4. A compound in accordance with claim 1 in which:
R 2 is alkoxy.
5. A compound in accordance with claim 1 in which:
R 3 is acyloxy.
6. A compound in accordance with claim 1 in which:
R 4 is alkyl.
7. A compound in accordance with claim 1 in which:
X is ═O.
8. A compound in accordance with claim 1 in which:
X is ═N—OR 5 .
9. A compound in accordance with claim 1 in which:
R 1 is —N(CH 3 ) 2 ;
R 2 is halogen;
R 3 is acyloxy;
R 4 is alkyl; and
X is ═O.
10. A compound in accordance with claim 9 in which:
R 2 is F.
11. A compound in accordance with claim 9 in which:
R 2 is Br.
12. A compound in accordance with claim 9 in which:
R 2 is Cl.
13. A compound in accordance with claim 9 in which:
R 4 is methyl.
14. A compound in accordance with claim 1 in which:
R 1 is —N(CH 3 ) 2 ;
R 2 is alkyl;
R 3 is acyloxy;
R 4 is alkyl; and
X is ═O.
15. A compound in accordance with claim 1 in which:
R 1 is —N(CH 3 ) 2 ;
R 2 is alkoxy;
R 3 is acyloxy;
R 4 is alkyl; and
X is ═O.
16. A compound in accordance with claim 15 in which:
R 2 is methoxy.
17. A compound in accordance with claim 15 in which:
R 2 is ethoxy.
18. A compound in accordance with claim 15 in which:
R 3 is acetoxy.