Claims
- 1. A cinnamoylamide derivative of the formula: ##STR33## Wherein R.sup.2 and R.sup.3 each independently represents a hydrogen or methyl group with the proviso that
- (i) when R.sup.2 represents a methyl group, R.sup.3 represents hydrogen and (R.sup.1).sub.n represents a member selected from the group consisting of 3-group 4-pentyl group, 4-neopentyl group, 4-(2-ethylbutyl) group and 4-(2-methylpentyl) group, or
- (ii) when R.sup.2 represents hydrogen, R.sup.3 represents a methyl group and (R.sup.1).sub.n represents a 3-pentyl group, or non-toxic salts therof.
- 2. A derivative according to claim 1, wherein
- (i) R.sub.2 represents a methyl group, R.sub.3 represents hydrogen and (R.sup.1).sub.n represents a member selected from the group consisting of 3-pentyl group and 4-pentyl group, or
- (ii) R.sup.2 represents hydrogen, R.sup.3 represents a methyl group and (R.sup.1).sub.n represents a 3-pentyl group.
- 3. A derivative according to claim 2, wherein R.sup.2 represents a methyl group, R.sup.3 represents hydrogen and (R.sup.1).sub.n represents a member selected from the group consisting of 3-pentyl group and 4-pentyl group.
- 4. A pharmaceutical composition for treating alopecia, acne or prostatic hypertrophy which comprises an effective amount of a cinnamoylaimide derivative of the formula (I) depicted in claim 1 or a non-toxic salt thereof, and a pharmaceutically acceptable carrier and/or coating.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 62-109722 |
May 1987 |
JPX |
|
SUMMARY
This application is a continuation of application Ser. No 191,194, filed May 6, 1988 now abandoned.
This invention is related to novel cinnamoylamide derivatives of the following general formula: ##STR2## (wherein all of the symbols are the same measuring as hereafter defined.) and inhibitory agents on 5.alpha.-reductase containing them as active ingredient.
So far, many theories are exposited such as (1) imbalance of hormones, (2) genetics, (3) circulatory failure, (4) nutrition, as the origin of androgenic alopecia.
And it has been also suggested that testosterone (androgenic hormone) played an important role on the generation of hairs.
The theory of Adachi at al in which the relation between testosterone and androgenic alopecia is proved by biochemical experiments, is as follows:
According to the theory it is thought that, at the results of the series of the phenomena, hairs in the growing phase shift to the resting phase, the terminal hairs change to the soft hairs, and the androgenic alopecia develops in the end.
A report by H. V. Schweikert supports this theory that large quantities of metabolites by 5.alpha.-reductase such as dihydro testosterone etc. in hair follicles of androgenic alopecia-patient exist more than that in females or healthy male.
It was reported that dihydrotestosterone converted from testosterone by 5.alpha.-reductase also plays in an important physiological role in the generate of acnes (acne, pimple etc.) other than androgenic alopecia. J. B. Hay et al reported that the metabolism of testosterone by 5.alpha.-reductase was enhanced in he affected part of acne aggravated, from the study in the flux between affected skin of acne-patient and healthy skin (See Br. J. Dermatol., 91. 123 (1974)).
G. Sansone et al found that synthetic ability of dihydrotestosterone from testosterone developed from two to twenty times in the affected part of acne-patient compared to that in healthy man, and they suggested that dihydrotestosterone generated by 5.alpha.-reductase greatly relates to the generation or aggravation of acne (See J. Invest. Dermatol., 56. 366 (1971)).
And, dihydrotestosterone is related to the hypertrophy of prostate. Cowan et al reported that much dihydrotestosterone existed in the prostate of prostatic hypertrophy-patient (See J. Steroid Biochemistry, 11. 609 (1979)). Recently, it was known that activity of 5.alpha.-reductase in prostate of prostatic hypertrophy-patient aggravated abnormally (See J. Clinical Endocrinol and Metabolism, 56, 139 (1983)).
From those informations it has been clear that dihydrotestosterone plays an important role in the generation and development of prostatic hypertrophy.
On the above background, recently, researches and developments of 5.alpha.-reductase inhibitors are carried out energetically and they are mainly steroids or derivatives thereof.
Widespread investigation has been carried out in order to discover compound which have a non-stroidal structure, and possess inhibitory activity on 5.alpha.-reductase. The present applicant have found that the above purpose can be accomplished by compounds wherein cinnamic acid or benzoic acids form amides with anilines, and then applicated the patents
For example, in the specification of Japanese Patent Kokai No. 61-126061, it was described that a very wide range of amide compounds possess inhibitory activity on 5.alpha.-reductase. Extracting part related closely to the compounds of the present invention of the general formula (1) in chemical structure from it, it is suggested that the compounds of the general formula: ##STR3## [wherein A.sup.a represents a binylene group unsubstituted or substituted by alkyl group(s) of from 1 to 10 carbon atom(s),
On the other hand, the group of compounds which are similar to the compounds of the prevent invention in chemical structure, is disclosed in the specification of Japanese Patent Kokai No. 51-1438 and France Patent Publication No. 2164481.
For example, in the specification of Japanese Patent Kokai No. 51-1438, it is disclosed that the compounds of the general formula ##STR6## [wherein R.sup.b1 and R.sup.b2 each represent a hydrogen atom or lower alkyl group,
Moreover, in the specification of France Patent Publication No. 2164481, it is disclosed that the compounds of the general formula: ##STR7## [wherein A.sup.c represents an alkylene group of from 1 to 3 carbon atom(s),
This time, the present inventors have synthesized newly the compounds which belong to the compounds of the general formula (A2) broadly and are not described specifically in the specification of Japanese Patent Kokai No. 61-126061, and confirmed that the compounds possess inhibitory activity on 5.alpha.-reductase. As the result, we, the present inventors have found the compounds which possess far more activity than we expected at the beginning and then completed the present invention. It can be quite unexpected that the compounds having remarkably superior activity are contained in the compounds of the general formula(A2)
The compounds of the general formula (I), of the prevent invention are not contained in the general formula (B), and the fact that the compounds of the general formula (B) possess anti-inflammatory acitivity never quite suggest that the compounds of the prevent invention possess inhibitory activity on 5.alpha.-reductase. Examining the specification of France Patent Kokai No. 2164481 in detail, we can understand that only one compound was synthesized in practice. Moreover, the fact that compounds of the general formula (C) possesses anti-inflammatory activity does not quite suggest that the compounds of the present invention possess inhibitory activity on 5.alpha.-reductase.
US Referenced Citations (1)
| Number |
Name |
Date |
Kind |
| 4026896 |
Harita et al. |
May 1977 |
|
Foreign Referenced Citations (4)
| Number |
Date |
Country |
| 173516 |
Mar 1986 |
EPX |
| 2515914 |
Nov 1975 |
DEX |
| 62-116657 |
Jun 1985 |
JPX |
| 62-198653 |
Sep 1987 |
JPX |
Continuations (1)
|
Number |
Date |
Country |
| Parent |
191194 |
May 1988 |
|
Patent Grant
5037852
