Claims
- 1. A compound of the formula: ##STR40## wherein: R.sup.1 is SO.sub.2 NR.sub.2.sub.4, SO.sub.2 NHR.sup.4 or benzyl;
- R.sup.2 and R.sup.3 are arranged in cis-configuration;
- R.sup.2 is phenyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of OH, halogen, nitro, cyano, SH, SR.sup.4, trihalo-C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 alkoxy and phenyl;
- R.sup.3 is phenyl substituted with --X--(CH.sub.2).sub.n --Y, wherein:
- X is a valency bond, O or S,
- n is an integer in the range of 1 to 12,
- Y is H, halogen, OH, OR.sup.4, NHR.sup.4, NR.sub.2.sup.4, NHCOR.sup.4, NHSO.sub.2 R.sup.4,CONHR.sup.4,
- CONR.sub.2.sup.4, COOH, COOR.sup.4, SO.sub.2 R.sup.4, SOR.sup.4, SONHR.sup.4, SONR.sub.2.sup.4, a pyrrolidinyl ring, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR.sup.4, trihalo-C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl and C.sub.1 -C.sub.6 -alkoxy; and
- R.sup.4 is C.sub.1 -C.sub.6 -alkyl;
- and optical and geometrical isomers, pharmaceutically acceptable esters, ethers and salts thereof.
- 2. A compound of the formula I: ##STR41## wherein: R.sup.1 is SO.sub.2 NR.sub.2.sup.4 or SO.sub.2 NHR.sup.4 ;
- R.sup.2 and R.sup.3 are arranged in cis-configuration;
- R.sup.2 is phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of OH, halogen, nitro, cyano, SH, SR.sup.4, trihalo-C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl and C.sub.1 -C.sub.6 -alkoxy;
- R.sup.3 is phenyl substituted with --X--(CH.sub.2).sub.n --Y, wherein:
- X is a valency bond, O or S,
- n is an integer in the range of 1 to 12,
- Y is H, OH, OR.sup.4, NHR.sup.4, NR.sub.2.sup.4, NHCOR.sup.4, NHSO.sub.2 R.sup.4, CONHR.sup.4, CONR.sub.2.sup.4, COOH, COOR.sup.4, SO.sub.2 R.sup.4, SOR.sup.4, SONHR.sup.4, SONR.sub.2.sup.4, a pyrrolidinyl ring, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR.sup.4, trihalo-C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl and C.sub.1 -C.sub.6 -alkoxy; and
- R.sup.4 is C.sub.1 -C.sub.6 -alkyl;
- and optical and geometrical isomers, pharmaceutically acceptable esters, ethers and salts thereof.
- 3. A compound according to claim 1 having the formula ##STR42## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above.
- 4. A compound according to claim 1 having the formula ##STR43## wherein R.sup.1 is as defined above and m is an integer from 0 to 10.
- 5. A compound according to claim 1 having the formula ##STR44## wherein R.sup.1 is as defined above and R.sup.6 represents one or more of the following substituents: methoxy, hydroxy, trifluormethyl, fluoro and chloro.
- 6. A compound according to claim 1 which is
- (.+-.)-(cis-3-(4-Methylphenyl)4-(4-(2-pyrrolidinoethoxy)phenyl)-chroman-7-yl) N,N-dimethylsulfamic acid ester.
- 7. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 or a pharmaceutical acceptable salt thereof and a pharmaceutical carrier or diluent.
- 8. The pharmaceutical composition according to claim 7 in the form of an oral dosage unit or parenteral dosage unit.
- 9. A method of treating estrogen deficiency associated with bone loss, osteoporosis, cardiovascular diseases, cognitive disorders, menopausal symptoms, incontinence, obesity, dysmenorrhea, dysfunctional uterine bleeding, acne, hirsutism, prostatic carcinoma, estrogen-dependent cancers, postpartum lactation, and threatened or habitual abortion, said method comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 1.
- 10. The method of claim 9, wherein the menopausal symptoms are flushing, urogenital atrophy, depression, mania, or schizophrenia.
Priority Claims (1)
Number |
Date |
Country |
Kind |
1200/96 |
Oct 1996 |
DKX |
|
CROSS-REFERENCE TO RELATED APPLICATIONS
The application claims priority under 35 U.S.C. 119 United States provisional application Ser. No. 60/031,239 filed Nov. 12, 1996 and Danish application serial no. 1200/96 Oct. 28, 1996, the contents of which are fully incorporated herein by reference.
US Referenced Citations (6)
Foreign Referenced Citations (2)
Number |
Date |
Country |
WO 9420098 |
Sep 1994 |
WOX |
WO 9621444 |
Jul 1996 |
WOX |
Non-Patent Literature Citations (3)
Entry |
Salman et al., J. Med. Chem., 26, pp. 592-595, (1983). |
Bundgaard "Design of prodrugs" Elsevier, p. 3-9, 1985. |
Durani et al. "a possible basis for structure-fuction relationship of estrogens" CA 95:109086, 1981. |