Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-05-05
1998-06-02
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514419, 544373, 548493, A61K 31405, A61K 31495, C07D20912, C07D40310
Patent
active
057600406
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP95/00599 filed Mar. 29, 1995.
TECHNICAL FIELD
The present invention relates to novel indole derivatives which have testosterone 5.alpha.-reductase inhibitory action and thus are effective in the treatment and/or prevention of diseases caused by overproduction of dihydrotestosterone, e.g., prostatic hypertrophy or accompanying urination disorder, male pattern alopecia, and acne; and which have .alpha..sub.1 -adrenergic receptor blocking action and thus are capable of selectively curing disorders regarding passage through the bladder neck to thereby improve urination disorder.
BACKGROUND ART
Testosterone 5.alpha.-reductase is an enzyme that reduces testosterone, a male hormone (androgen), into dihydrotestosterone. The produced dihydrotestosterone has been elucidated to play an important role in the mechanism of the generation and progress of prostatic hypertrophy, male pattern alopecia, and acne (J. Steroid Biochemistry, 11, 609 (1979), J. Clinical Endocrinol and Metabolism, 56, 139 (1983), and Japanese Patent Application Laid-Open (kokai ) No. 1-139558). Indoles are known as compounds that exhibit testosterone 5.alpha.-reductase inhibitory activities, (Japanese Patent Application Laid-Open (kokai) No. 4-244061, WO93/02050).
.alpha.-Adrenergic receptors are known to participate in contraction of smooth muscles. Particularly, recent research has revealed that .alpha..sub.1 -adrenergic receptors strongly participate in contraction of the sphincter in the human bladder neck (J. Urol., 134, 396 (1985)). Therefore, blockers of the receptors are considered to serve as drugs that are capable of selectively treating urination disorders and frequent urination accompanied by prostatic hypertrophy. As compounds that have a blocking action against such .alpha..sub.1 -adrenergic receptors, there are known piperazine derivatives (WO89/12634, WO90/03972).
Disurea, which aged people frequently suffer, is caused by constriction of urethra due to the tonus of sympathetic nerves present in the bladder neck or by urinary obstruction associated with prostatic hypertrophy, and makes urination difficult. In recent years, disurea has been treated by the combined use of an .alpha..sub.1 -adrenergic receptor blocking agent and an antiandrogenic agent. However, this is not satisfactory in view of the drug administration schedule.
Therefore, it is desired to develop drugs having both benefits of symptomatic therapy, which exerts immediate effects as exerted by .alpha..sub.1 -adrenergic receptors, and of radical therapy, which exhibits its effect slowly but radically, as in the case of testosterone 5.alpha.-reductase inhibitors. However, compounds having both .alpha..sub.1 -adrenergic receptor blocking action and testosterone 5.alpha.-reductase inhibitory action have so far not been known.
DISCLOSURE OF THE INVENTION
The present inventors conducted careful studies toward solving the above problems, and surprisingly found that the indole derivatives (1) described below possess strong actions of both blocking .alpha..sub.1 -adrenergic receptors and inhibiting testosterone 5.alpha.-reductases, and thus are useful for the treatment of prostatic hypertrophy and disorders accompanying the same, such as urination disorder, alopecia, and acne. The present invention was accomplished based on this finding.
Accordingly, the present invention provides an indole derivative represented by the following formula (1) or a salt thereof: ##STR2## wherein R.sup.1 represents lower alkyl; R.sup.2 represents hydrogen or phenyl which may be substituted by at least one lower alkyl, lower alkoxy or a halogen atom; R.sup.3 represents hydrogen, lower alkyl, lower alkoxy, or phenylalkyloxy which may be substituted by halogen or lower alkyl; R.sup.4 represents hydrogen, lower alkyl or lower alkoxy; R.sup.5 represents hydrogen or lower alkyl; and n represents an integer of 1 to 5.
The present invention also provides an .alpha..sub.1 -adrenergic receptor blocker and testosterone 5.alpha.-reductase inhibitor comprising as an
Kurimoto Tadashi
Sato Hiroki
Takei Mineo
Yoshida Kiyoshi
Oswecki Jane C.
Richter Johann
Zeria Pharmaceutical Co. Ltd.
LandOfFree
Indole derivative for treating overproduction of dihydrotestoste does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Indole derivative for treating overproduction of dihydrotestoste, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Indole derivative for treating overproduction of dihydrotestoste will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1460063