# US 5,705,507 A · Aplha-substituted-3-benzyl-benzofurans

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- Number: US 5,705,507 A
- Document ID: US5705507A
- Status: Granted
- Kind: A
- Application number: 08/536,313
- Filed: 1995-09-29
- Granted: 1998-01-06
- Earliest claimed: 1995-03-10
- Assignees: Eli Lilly and Company
- Inventors: Brian S. Muehl
- Web page: https://patentgrep.com/patent/US5705507A

## CPC

- C07D 307/80: Radicals substituted by oxygen atoms
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 19/10: for osteoporosis
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 307/81: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- Y10S 206/828: Medicinal content
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

This invention relates to the fields of pharmaceutical and organic chemistry and provides novel 3-benzyl-benzofurans which are .alpha.-substituted with ether, thioether, amino, hydrazino, cyano or halo that are useful for the treatment of the various medical indications associated with post-menopausal syndrome, as well as estrogen dependent diseases including cancer of the breast, uterus and cervix. The present invention further relates to intermediate compounds and processes useful for preparing the pharmaceutically active compounds of the present invention, and pharmaceutical compositions.

## Claims

### Claim 1

A compound of the formula ##STR33## wherein R.sub.1 is OH, OCO (C.sub.1 -C.sub.6 alkyl), OCO (aryl), OSO.sub.2 (C.sub.4 -C.sub.6 alkyl), OCOO (C.sub.1 -C.sub.6 alkyl), OCOO (aryl), OCONH (C.sub.1 -C.sub.6 alkyl), or OCON (C.sub.1 -C.sub.6 alkyl).sub.2 ;
R.sub.2 is aryl, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or 4-cyclohexanol;
R.sub.3 is O (CH.sub.2).sub.2 or O (CH.sub.2).sub.3 ;
R.sub.4 and R.sub.5 are optionally CO (CH.sub.2).sub.2 CH.sub.3, CO (CH.sub.2).sub.3 CH.sub.3, C.sub.1 -C.sub.6 alkyl, or R.sub.4 and R.sub.5 combine to form, with the nitrogen to which they are attached, piperidine, morpholine, pyrrolidine, 3-methylpyrrolidine, 3,3-dimethylpyrrolidine, 3,4-dimethylpyrollidine, azepine, or pipecoline;
R.sub.6 is ##STR34## wherein each of R.sub.7 and R.sub.8 is taken separately and represents H, C.sub.1 -C.sub.6 -alkyl, 2-hydroxyethyl, or 2-fluoroethyl, with the proviso that (1) R.sub.7 and R.sub.8 are not both H;
(2) R.sub.7 and R.sub.8 are not both C.sub.1 -C.sub.6 -alkyl; and
(3) when either R.sub.7 or R.sub.8 is H, then the other is not C.sub.1 -C.sub.6 -alkyl;
or both R.sub.7 and R.sub.8 are taken together with the nitrogen and form a ring which is pyrrolidine, piperidine, azepine, or morpholine and which may optionally be substituted by one or two methyl groups, or ##STR35## wherein each of R.sub.10 and R.sub.11 is taken separately and represents H or C.sub.1 -C.sub.2, or both R.sub.10 and R.sub.11 are taken together with the nitrogen and represent a ring which is a pyrrolidine, piperidine, azepine or morpholine and which may optionally be substituted by one or two methyl groups, and R.sub.12 is hydrogen, methyl, or ethyl; and pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1, and, optionally, an effective amount of estrogen or progestin, in combination with a pharmaceutically acceptable carrier, diluent or excipient.

### Claim 3 (depends on 1)

A method for alleviating the symptoms of post-menopausal syndrome comprising administering to a woman in need of such treatment an effective amount of a compound of claim 1.

### Claim 4 (depends on 3)

A method according to claim 3 wherein the post-menopausal syndrome pathological condition is osteoporosis.

### Claim 5 (depends on 3)

A method according to claim 3 wherein the post-menopausal syndrome pathological condition is related to a cardiovascular disease.

### Claim 6 (depends on 1)

A method for inhibiting uterine fibroid disease comprising administering to a woman in need of such treatment an effective amount of a compound of claim 1.

### Claim 7 (depends on 1)

A method for inhibiting endometriosis comprising administering to a woman in need of such treatment an effective amount of a compound of claim 1.

### Claim 8 (depends on 1)

A method for inhibiting aortal smooth muscle cell proliferation comprising administering to a human in need of such treatment an effective amount of a compound of claim 1.

### Claim 9 (depends on 1)

A method for inhibiting restenosis comprising administering to a human in need of such treatment an effective amount of a compound of claim 1.

### Claim 10 (depends on 1)

An article of manufacture comprising packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent is effective for treatment of a malady selected from 1) a various medical indication associated with postmenopausal syndrome, and 2) estrogen dependent diseases, and wherein said packaging material comprises a label which indicates that said pharmaceutical agent can be used for treating one of said maladies, and wherein said pharmaceutical agent is selected from the group consisting of a compound of formula (I) of claim 1.