JPS5953417A - Testosterone-5alpha-reductase inhibitor - Google Patents

Testosterone-5alpha-reductase inhibitor

Info

Publication number
JPS5953417A
JPS5953417A JP16427582A JP16427582A JPS5953417A JP S5953417 A JPS5953417 A JP S5953417A JP 16427582 A JP16427582 A JP 16427582A JP 16427582 A JP16427582 A JP 16427582A JP S5953417 A JPS5953417 A JP S5953417A
Authority
JP
Japan
Prior art keywords
testosterone
5alpha
formula
decen
bicyclo
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
JP16427582A
Other languages
Japanese (ja)
Other versions
JPH0380769B2 (en
Inventor
Toshio Nishiyama
西山　敏夫
Shinichi Hirama
平間　伸一
Makoto Uzuka
宇塚　誠
Keisuke Nakajima
啓介 中嶋
Kenichi Tomita
健一 富田
Shoji Nakamura
祥二 中村
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shiseido Co Ltd
Original Assignee
Shiseido Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shiseido Co Ltd filed Critical Shiseido Co Ltd
Priority to JP16427582A priority Critical patent/JPS5953417A/en
Publication of JPS5953417A publication Critical patent/JPS5953417A/en
Publication of JPH0380769B2 publication Critical patent/JPH0380769B2/ja
Granted legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

PURPOSE:To provide the titled inhibitor free from the hormone-like action, applicable externally and safely for a long period, and useful for the remedy and prevention of the symptoms such as male pattern baldness, etc., by using 5,6- dimethyl-8-isopropenyl-bicyclo [4,4,0]-decen-1-one as an active component. CONSTITUTION:The objective inhibitor contains 5,6-dimethyl-8-isopropenyl-bicyclo [4,4,0]decen-1-one of formula as an active component. The above compound of formula is a sesquiterpene contained in grape fruit oil, etc., absolutely free from hormone-like action, and devoid of other undersirable side effects. The testosterone-5alpha-reductase inhibiting action of the compound of formula has been demonstrated by determining the amount of testosterone reduced to 5alpha-dihydrotestosterone using human hair root.

Description

【発明の詳細な説明】 本発明は、新規なるテストステロン−５α−しダクター
ゼ阻害剤に関するものである。男性型の禿頭、粗毛症、
尋常性能ｊＭ、脂漏などの生理学１の徴候は、代謝系に
男性ホルモンが過剰にｉ　ｆ【１ｆされることに起因す
る男性ホルモン刺激の増大に基づいていることが知られ
ている。また最近、Ｇ　、ｆｌ、！、皮脂腺をはしめい
くつかの器官において男性ホルモン活性の本体は、５α
−ジヒドロテストス〜ア■」ンでアリ、これは標的器官
においてテストステロンがデス１ステロンー５α−レダ
クターゼにより還元されることによって生成することが
周知になっている。その゛ため、男性ホルモン１テリ激
の増大に起因する男性型の禿頭・粗毛症、尋常性座癒、
脂漏などの徴候は、テストステロン−５α−レダクター
ゼを阻害することにより低減あるいは防１１−すること
ができると考えられ、テストステロン−５α−しダクタ
ーゼを特異的に阻害するいくつかの阻害剤が見出され、
また合成されてきた。例えば黄体ホルモンプロゲステロ
ンはテストステロン−５α−レダクターゼを大きく阻害
することが周知であるが、その反面、プロゲステロン自
身の持ツ女性ポルモン作用が発現し、乳房の肥大、澤丸
委縮、精力減退なとの好ましくない作用が現われてくる
。また、乍までに新規に合成された阻害剤は、ステロイ
１．’　ｊＪＩ造あるいはステロイド類似構造を持って
おり、やはり好ましくないホルモン様作用を多少なりと
も有しているという欠点があった。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel testosterone-5α-ductase inhibitor. Male pattern baldness, hair loss,
It is known that symptoms of Physiology 1, such as normal performance jM and seborrhea, are based on increased stimulation of androgens caused by excessive production of androgens in the metabolic system. Recently, G, fl,! , the main body of male hormone activity in several organs including the sebaceous glands is 5α
It is well known that dihydrotestosterone is produced by the reduction of testosterone by des1sterone-5α-reductase in the target organ. As a result, male-pattern baldness and coarse hair, acne vulgaris,
It is thought that symptoms such as seborrhea can be reduced or prevented by inhibiting testosterone-5α-reductase, and several inhibitors have been discovered that specifically inhibit testosterone-5α-reductase. is,
It has also been synthesized. For example, it is well known that progesterone, a progesterone, greatly inhibits testosterone-5α-reductase, but on the other hand, progesterone itself exhibits its own female pormon effect, which causes undesirable effects such as enlargement of the breasts, atrophy of the Sawa's circle, and decreased energy. Effects that were previously absent will appear. In addition, the newly synthesized inhibitors are steroid 1. It has a JI structure or a steroid-like structure, and it also has the disadvantage of having some undesirable hormone-like effects.

（以下全白） 本発明者らは、ホルモン様作用を全く持たないテストス
テロン−５α−レダクターゼ阻害剤について鋭意研究を
重ねた結果、５．６−シメチルー８　”　イア　フｏベ
ニル−ビンクロ（４，４，０：ＩＶ’セン−１−オン−
３がテストステロン−５α−レダクターゼを阻害するこ
とを見出し本発明を完成するに致った。即ち、 本発明は式（１）で表わされる５、６−シメチルー８−
インプロペニル−ビシクロ（４，４，０）デセン−１−
オン−３からなるテストステロン−５α−レダクターゼ
阻害剤である。(Hereinafter referred to as "all white") As a result of extensive research into a testosterone-5α-reductase inhibitor that has no hormone-like effects, the present inventors discovered that 5,6-cymethyl-8'' iafbenyl-binculo (4,4 ,0:IV'sen-1-one-
The present invention was completed by discovering that 3 inhibits testosterone-5α-reductase. That is, the present invention provides 5,6-cymethyl-8- represented by formula (1).
Impropenyl-bicyclo(4,4,0)decene-1-
It is a testosterone-5α-reductase inhibitor consisting of 1-3.

（以下余白） ５．６−シメチルー８−インプロペニル−ビシクロ（４
，４，０）デセン−１−オン−３はグレープフルーツオ
イル等に含有されているセスキテルペンケトンであって
、ホルモン作用は一切持たず、また他の好ましくない副
作用も有していない。(Left below) 5.6-dimethyl-8-impropenyl-bicyclo(4
, 4, 0) Decen-1-one-3 is a sesquiterpene ketone contained in grapefruit oil and the like, and has no hormonal effects or other undesirable side effects.

従って、本発明の５．６−シメチルー８−インプロペニ
ル−ビシクロ（４，４’、ｏ）デセン−１−オン−３を
テストステロン−５α−レダクターゼ阻害剤として使用
しても、ホルモン様作用は全く持たず、しかも長期にわ
たり継続的に外用しても、安全性には問題がないという
すぐれた利点を有している。Therefore, even when the 5,6-dimethyl-8-impropenyl-bicyclo(4,4',o)decen-1-one-3 of the present invention is used as a testosterone-5α-reductase inhibitor, it does not exhibit any hormone-like effects. Moreover, it has the excellent advantage of being safe even when used externally for a long period of time.

次に、本発明の５〜６−ジメテルー８−イソプロペ１ル
ービシクロ（４，４，０）デセン−１−オン−３のテス
トステロン−５α−レダクターゼ阻害作用を実証する実
験例を以下に具体的に示す。Next, an experimental example demonstrating the testosterone-5α-reductase inhibitory effect of 5-6-dimethe-8-isoprope-1-rubicyclo(4,4,0)decen-1-one-3 of the present invention will be specifically shown below. .

（以下余白） 高安らの方法（Ｓ、　Ｔａｋａｙａｓｕ　、　Ｋ、　Ａ
ｄａｃｈｉ　、ザ・ジャー９ ナル拳オブ傘クリニカル・エンドクルノロシー崇エント
メタボリズム（Ｊ、　０１ｉｎ　、　Ｅｎｄｏｃｒｉｎ
ｏｌ　、Ｍｅｔａへ、）。(Left below) Takayasu's method (S, Takayasu, K, A
dachi, The Jar 9 Naruken of Umbrella Clinical Endocrinology Entometabolism (J, 01in, Endocrin
ol, to Meta,).

第ヌ巻、第１０９８−１１０１項、１９９２年〕に従い
、人毛根を用い、テストステロンが５α−ジヒドロテス
トステロンに還元されるＶｉ′ｒを測定し、５．６−シ
メチルー８−イソプロペミル−ビシクロ（４，４，０）
デセン−１−オン−３によるテストステロン−５α−レ
ダクターゼ阻害作用を検討し、表１に示した。Vol. 1, No. 1098-1101, 1992], using human hair roots, the Vi′r at which testosterone is reduced to 5α-dihydrotestosterone was measured, and 5,6-dimethyl-8-isopropemyl-bicyclo(4, 4,0)
The inhibitory effect of decen-1-one-3 on testosterone-5α-reductase was investigated and is shown in Table 1.

表１　人毛根テストステロンー５α−レダクタ−（以下
余白） また、ハムスターの皮脂腺を用いる高安らの方法〔高安
　進、板見　智、西日本皮膚利、第ぐ巻、第１．２１５
−１２１．７頁１９８１年〕に基づいて、皮脂腺のテス
トステロン−５α−レダクターゼを阻害する５、６−シ
メチルー８−インプロペペルービシクロ〔４，４，Ｏ）
デセン−１−オン−３の効果を表２に示した。ＢＩ４害
率０算出方法は表−１と同様である。Table 1 Human hair root testosterone-5α-reductor (blank below) Also, Takayasu's method using hamster sebaceous glands [Susumu Takayasu, Satoshi Itami, Nishinippon Dermatology, Vol. 2, No. 1.215
-121.7, 1981], 5,6-cymethyl-8-impropeperubicyclo[4,4,O] inhibits testosterone-5α-reductase in the sebaceous gland.
Table 2 shows the effects of decen-1-one-3. The method for calculating BI4 harm rate 0 is the same as in Table-1.

表２　ハムスター皮脂腺テストステロン−５α−前記表
１および表２において、人毛根・ハムスター皮脂腺にお
ける５、６−シメチルー８−インプロペヌル−ビシクロ
（４，４，０）デセン−１−オン−３のテストステロン
−５α−レダクターゼ阻害作用が明らかに認められた。Table 2 Hamster sebaceous gland Testosterone-5α - In Tables 1 and 2 above, Testosterone-5α of 5,6-dimethyl-8-impropenul-bicyclo(4,4,0)decen-1-one-3 in human hair roots and hamster sebaceous glands - Reductase inhibitory effect was clearly observed.

このように、５．６−シメチルー８−インプロペペルー
ビシクロ（４，４，０）デセン−１−オン−３はテスト
ステロン−５α−レダクターゼ阻害作用ヲ有するのみな
らず、ホルモン様作用は−ｕＪもだ１″安全性も高いと
いうすぐれた特徴を有してＯＺ）。Thus, 5,6-cymethyl-8-impropeperubicyclo(4,4,0)decen-1-one-3 not only has an inhibitory effect on testosterone-5α-reductase, but also has a hormone-like effect on -uJ. It has the excellent feature of being highly safe (OZ).

特許出願人　　株式会社　資　生　堂Patent applicant: Shiseido Co., Ltd.

Claims (1)

【特許請求の範囲】[Claims] （１）　　式（Ｉ）で表わされる５、６−シメチルー８
−インプロペニル−ピンクｏ（４，４，０）７’セン−
１−オン−３からなるテストステロン−５α−レダクタ
ーゼ阻害剤。 （以下余白）(1) 5,6-cymethyl-8 represented by formula (I)
-impropenyl-pink o(4,4,0)7'sen-
Testosterone-5α-reductase inhibitor consisting of 1-one-3. (Margin below)
JP16427582A 1982-09-21 1982-09-21 Testosterone-5alpha-reductase inhibitor Granted JPS5953417A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP16427582A JPS5953417A (en) 1982-09-21 1982-09-21 Testosterone-5alpha-reductase inhibitor

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP16427582A JPS5953417A (en) 1982-09-21 1982-09-21 Testosterone-5alpha-reductase inhibitor

Publications (2)

Publication Number Publication Date
JPS5953417A true JPS5953417A (en) 1984-03-28
JPH0380769B2 JPH0380769B2 (en) 1991-12-26

Family

ID=15789986

Family Applications (1)

Application Number Title Priority Date Filing Date
JP16427582A Granted JPS5953417A (en) 1982-09-21 1982-09-21 Testosterone-5alpha-reductase inhibitor

Country Status (1)

Country Link
JP (1) JPS5953417A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4937237A (en) * 1988-12-23 1990-06-26 Smithkline Beckman Corporation Phosphinic acid substituted aromatic steroids as inhibitors of steroid 5-60 -reductase
US4970205A (en) * 1988-12-23 1990-11-13 Smithkline Beecham Corporation Sulfonic acid substituted aromatic steroids as inhibitors of steroid 5-α-reductase
EP0467660A2 (en) * 1990-07-20 1992-01-22 Yutaka Miyauchi Use of d-limonenes as testosterone-5-alpha-reductase inhibitor and as hair grower

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4937237A (en) * 1988-12-23 1990-06-26 Smithkline Beckman Corporation Phosphinic acid substituted aromatic steroids as inhibitors of steroid 5-60 -reductase
US4970205A (en) * 1988-12-23 1990-11-13 Smithkline Beecham Corporation Sulfonic acid substituted aromatic steroids as inhibitors of steroid 5-α-reductase
EP0467660A2 (en) * 1990-07-20 1992-01-22 Yutaka Miyauchi Use of d-limonenes as testosterone-5-alpha-reductase inhibitor and as hair grower
EP0467660A3 (en) * 1990-07-20 1992-07-22 Yutaka Miyauchi Use of d-limonenes as testosterone-5-alpha-reductase inhibitor and as hair grower

Also Published As

Publication number Publication date
JPH0380769B2 (en) 1991-12-26

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