JPH06321782A - Steroidal compound - Google Patents

Steroidal compound

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Publication number
JPH06321782A
JPH06321782A JP11276093A JP11276093A JPH06321782A JP H06321782 A JPH06321782 A JP H06321782A JP 11276093 A JP11276093 A JP 11276093A JP 11276093 A JP11276093 A JP 11276093A JP H06321782 A JPH06321782 A JP H06321782A
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Japan
Prior art keywords
linear
branched
group
carcinogenic
ethyl acetate
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JP11276093A
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Japanese (ja)
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JP3584050B2 (en
Inventor
Koichi Shudo
紘一 首藤
Yasuyuki Endo
泰之 遠藤
Yuichi Hashimoto
祐一 橋本
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Abstract

PURPOSE:To obtain an inhibitor against carcinogenic promoters having high affinity for carcinogenic promoter-bound protein CN-TPBP, excellent in carcinogenic promoter-inhibitory effect, thus useful as a carcinogenic inhibitor, etc., containing, as active ingredient, a specific compound. CONSTITUTION:This inhibitor against carcinogenic promoters contains, as active ingredient, a compound of the formula [X is O or OH; R is O-CO-R<1> or CHR<2>-R<3> (R<1> is alkyl, alkenyl, aralkyl, etc.; R<2> is H or lower alkyl; R<3> is alkyl, alkenyl, alkoxyl, alkenyloxy, aralkyl, phenyl, etc.)] such as 3beta,5alpha-dihydroxy-23,24- bisnorcholan-6-one. It is preferable that the dose of the active ingredient be 0.1-10mg a day per adult.

Description

【発明の詳細な説明】Detailed Description of the Invention

【０００１】[0001]

【産業上の利用分野】本発明は、発がんプロモーター阻
害剤に関する。さらに詳しくは、レセプター蛋白に対す
る発がんプロモーターの結合を阻害することができ、発
がん抑制剤として有用な発がんプロモーター阻害剤に関
する。TECHNICAL FIELD The present invention relates to a carcinogenic promoter inhibitor. More specifically, it relates to a carcinogenic promoter inhibitor which can inhibit the binding of a carcinogenic promoter to a receptor protein and is useful as a carcinogenic suppressor.

【０００２】[0002]

【従来の技術】発がんプロモーターは、それ自身ではが
んを引き起こさないが、発がん性物質により惹起された
生物学的変化を増幅・修飾して、最終的な発がん状態に
至らしめる物質である。その代表的な物質として、12-O
−テトラデカノイル−ホルボール 13-アセテート（ＴＰ
Ａ）等のホルボールエステル（ジテルペン化合物）やテ
レオシジン（インドールアルカロイド）を挙げることが
できる。これらの発がんプロモーターが結合する細胞内
レセプターの一つとして、カルシウム依存性蛋白質リン
酸化酵素（ＰＫＣ）が知られている。しかしながら、蛋
白質リン酸化酵素の基質特異性は低いこと、ならびに蛋
白質リン酸化酵素活性化の情報が核内に伝達される機構
は明らかではなく蛋白質リン酸化酵素の阻害剤は必ずし
も発がんを抑制しないことから、これらの発がんプロモ
ーターの細胞内レセプターとして、蛋白質リン酸化酵素
以外のレセプターの存在が強く示唆されていた。BACKGROUND OF THE INVENTION A carcinogenic promoter is a substance that does not cause cancer by itself, but amplifies and modifies a biological change caused by a carcinogenic substance to reach a final carcinogenic state. 12-O is a typical substance
-Tetradecanoyl-phorbol 13-acetate (TP
Examples thereof include phorbol ester (diterpene compound) such as A) and teleocidin (indole alkaloid). Calcium-dependent protein kinase (PKC) is known as one of intracellular receptors to which these carcinogenic promoters bind. However, since the protein phosphorylase has low substrate specificity, and the mechanism by which information on protein kinase activation is transmitted into the nucleus is not clear, and inhibitors of protein kinase do not necessarily suppress carcinogenesis. The existence of receptors other than protein kinases as intracellular receptors for these oncogenic promoters has been strongly suggested.

【０００３】本発明者は、これらの発がんプロモーター
が結合する細胞内レセプターを検索するうち、蛋白質リ
ン酸化酵素とは異なる複数の細胞内レセプター（発がん
プロモーター結合蛋白：Tumor Promoter Binding Prote
ins (TBPs), Biochem. Biophys. Res. Com. 166, 1126-
1132, 1990）を発見し、さらに、それらの細胞内レセプ
ターのうちの一つが、リガンド依存的に細胞質内から核
内へと移行する性質を有する発がんプロモーター特異的
結合蛋白であることを見出し、CN-TPBP(Cytosolic-Nucl
ear Tumor Promoter-Specific Binding Protein)と命名
した（Jpn. J.Cancer Res. 82, 665-675, 1991 ）。The present inventor searched for intracellular receptors to which these oncogenic promoters bind, and found a plurality of intracellular receptors different from protein kinases (oncogenic promoter binding protein: Tumor Promoter Binding Prote
ins (TBPs), Biochem. Biophys. Res. Com. 166, 1126-
1132, 1990) and further discovered that one of those intracellular receptors is a carcinogenic promoter-specific binding protein having the property of translocation from the cytoplasm to the nucleus in a ligand-dependent manner. -TPBP (Cytosolic-Nucl
ear Tumor Promoter-Specific Binding Protein) (Jpn. J. Cancer Res. 82, 665-675, 1991).

【０００４】[0004]

【発明が解決しようとする課題】本発明は、上記の発が
んプロモーター特異的結合蛋白CN-TPBP に対する発がん
プロモータの結合を拮抗的に阻害し、発がんプロモータ
ーの作用を抑制する物質を提供することを目的としてい
る。The object of the present invention is to provide a substance that competitively inhibits the binding of a carcinogenic promoter to the above-mentioned carcinogenic promoter-specific binding protein CN-TPBP and suppresses the action of the carcinogenic promoter. I am trying.

【０００５】[0005]

【課題を解決するための手段】本発明者は、上記の課題
を解決すべく、種々の化合物について発がんプロモータ
ー特異的結合蛋白CN-TPBP に対する親和性を検索したと
ころ、特定のステロイド化合物類が、発がんプロモータ
ー特異的結合蛋白CN-TPBP に対して強い親和性を示し、
CN-TPBP に対するＴＰＡ等の発がんプロモータの結合を
拮抗的に阻害することを見出した。本発明は、上記の知
見に基づいて完成されたものである。本発明の発がんプ
ロモーター阻害剤は、ホルボールエステルやテレオシジ
ンのような蛋白質リン酸化酵素活性化作用を有しないの
で、発がんプロモーターの作用を抑制することができ、
発がん抑制に有用である。本発明の阻害剤に有効成分と
して含有される化合物はステロイド系化合物であり、以
下の式（Ｉ）：Means for Solving the Problems In order to solve the above-mentioned problems, the present inventor searched various compounds for affinities for a carcinogenic promoter-specific binding protein CN-TPBP, and found that specific steroid compounds were Has a strong affinity for the carcinogenic promoter-specific binding protein CN-TPBP,
It was found that the binding of a carcinogenic promoter such as TPA to CN-TPBP is competitively inhibited. The present invention has been completed based on the above findings. The carcinogenic promoter inhibitor of the present invention does not have a protein phosphatase activating effect such as phorbol ester or tereosidine, and thus can suppress the action of the carcinogenic promoter,
It is useful for suppressing carcinogenesis. The compound contained as an active ingredient in the inhibitor of the present invention is a steroid compound and has the following formula (I):

【０００６】[0006]

【化３】 で示される３β、５α−ジヒドロキシアンドロスタン−
６−オン誘導体である。式中、X は＝O または -OHを示
し、R は-O-CO-R1または-CHR2-R3を示す（R1は直鎖また
は分枝したアルキル基、直鎖または分枝したアルケニル
基、直鎖または分枝したアラルキル基、あるいは置換ま
たは非置換フェニル基であり、R2は水素原子、あるいは
直鎖または分枝した低級アルキル基であり、R3は直鎖ま
たは分枝したアルキル基、直鎖または分枝したアルケニ
ル基、直鎖または分枝したアルコキシ基、直鎖または分
枝したアルケニルオキシ基、直鎖または分枝したアラル
キル基、あるいは置換または非置換フェニル基であ
る）。上記の一般式（Ｉ）中、ステロイド骨格の３位お
よび５位の水酸基はそれぞれβ配置およびα配置であ
り、X が -OHを示す場合には、６位の水酸基はβ配置を
とることが好ましい。R はβ配置でステロイド骨格に置
換することが好ましい。[Chemical 3] 3β, 5α-dihydroxyandrostane represented by
It is a 6-one derivative. In the formula, X represents = O or -OH, and R represents -O-CO-R 1 or -CHR 2 -R 3 (R 1 is a linear or branched alkyl group, a linear or branched alkyl group An alkenyl group, a linear or branched aralkyl group, or a substituted or unsubstituted phenyl group, R 2 is a hydrogen atom, or a linear or branched lower alkyl group, and R 3 is a linear or branched An alkyl group, a straight-chain or branched alkenyl group, a straight-chain or branched alkoxy group, a straight-chain or branched alkenyloxy group, a straight-chain or branched aralkyl group, or a substituted or unsubstituted phenyl group) . In the above general formula (I), the 3-position and 5-position hydroxyl groups of the steroid skeleton have β-configuration and α-configuration, respectively, and when X represents -OH, the 6-position hydroxyl group may have β-configuration. preferable. It is preferred that R 3 be substituted in the β configuration on the steroid skeleton.

【０００７】式（Ｉ）で示される化合物として、例えば
以下の表１に示す化合物を挙げることができるが、本発
明の阻害剤に含まれる化合物はこれらの化合物に限定さ
れることはない。Examples of the compound represented by the formula (I) include the compounds shown in Table 1 below, but the compounds contained in the inhibitor of the present invention are not limited to these compounds.

【０００８】[0008]

【表１】 X R X R ──────────────────────────────────── ＝O -O-CO-CH3 ＝O -CH(CH3)-CH3 ＝O -O-CO-CH2CH3 ＝O -CH(CH3)-CH2CH3 ＝O -O-CO-(CH2)2CH3 ＝O -CH(CH3)-(CH2)2CH3 ＝O -O-CO-(CH2)3CH3 ＝O -CH(CH3)-(CH2)3CH3 ＝O -O-CO-(CH2)4CH3 ＝O -CH(CH3)-(CH2)4CH3 ＝O -O-CO-(CH2)5CH3 ＝O -CH(CH3)-(CH2)5CH3 ＝O -O-CO-(CH2)6CH3 ＝O -CH(CH3)-(CH2)6CH3 ＝O -O-CO-(CH2)7CH3 ＝O -CH(CH3)-(CH2)7CH3 ＝O -O-CO-(CH2)8CH3 ＝O -CH(CH3)-(CH2)8CH3 ＝O -O-CO-(CH2)9CH3 ＝O -CH(CH3)-(CH2)9CH3 ＝O -O-CO-(CH2)10CH3 ＝O -CH(CH3)-(CH2)10CH3 ＝O -O-CO-(CH2)11CH3 ＝O -CH(CH3)-(CH2)11CH3 ＝O -O-CO-(CH2)12CH3 ＝O -CH(CH3)-(CH2)12CH3 ＝O -O-CO-CH(CH3)2 ＝O -CH(CH3)-CH(CH3)2 ＝O -O-CO-CH2CH(CH3)2 ＝O -CH(CH3)-CH2CH(CH3)2 ＝O -O-CO-(CH2)2CH(CH3)2 ＝O -CH(CH3)-(CH2)2CH(CH3)2 ＝O -O-CO-(CH2)3CH(CH3)2 ＝O -CH(CH3)-(CH2)3CH(CH3)2 ＝O -O-CO-(CH2)4CH(CH3)2 ＝O -CH(CH3)-(CH2)4CH(CH3)2 ＝O -O-CO-(CH2)5CH(CH3)2 ＝O -CH(CH3)-(CH2)5CH(CH3)2 ＝O -O-CO-(CH2)6CH(CH3)2 ＝O -CH(CH3)-(CH2)6CH(CH3)2 ＝O -O-CO-(CH2)7CH(CH3)2 ＝O -CH(CH3)-(CH2)7CH(CH3)2 ＝O -O-CO-(CH2)8CH(CH3)2 ＝O -CH(CH3)-(CH2)8CH(CH3)2 ＝O -O-CO-(CH2)9CH(CH3)2 ＝O -CH(CH3)-(CH2)9CH(CH3)2 ＝O -O-CO-(CH2)10CH(CH3)2 ＝O -CH(CH3)-(CH2)10CH(CH3)2 -OH -O-CO-CH3 ＝O -CH(CH3)-O-CH3 -OH -O-CO-CH2CH3 ＝O -CH(CH3)-O-CH2CH3 -OH -O-CO-(CH2)2CH3 ＝O -CH(CH3)-O-(CH2)2CH3 -OH -O-CO-(CH2)3CH3 ＝O -CH(CH3)-O-(CH2)3CH3 -OH -O-CO-(CH2)4CH3 ＝O -CH(CH3)-O-(CH2)4CH3 -OH -O-CO-(CH2)5CH3 ＝O -CH(CH3)-O-(CH2)5CH3 -OH -O-CO-(CH2)6CH3 ＝O -CH(CH3)-O-(CH2)6CH3 -OH -O-CO-(CH2)7CH3 ＝O -CH(CH3)-O-(CH2)7CH3 -OH -O-CO-(CH2)8CH3 ＝O -CH(CH3)-O-(CH2)8CH3 -OH -O-CO-(CH2)9CH3 ＝O -CH(CH3)-O-(CH2)9CH3 -OH -O-CO-(CH2)10CH3 ＝O -CH(CH3)-O-(CH2)10CH3 -OH -O-CO-(CH2)11CH3 ＝O -CH(CH3)-O-(CH2)11CH3 -OH -O-CO-(CH2)12CH3 ＝O -CH(CH3)-O-(CH2)12CH3 -OH -O-CO-CH(CH3)2 ＝O -CH(CH3)-O-CH(CH3)2 -OH -O-CO-CH2CH(CH3)2 ＝O -CH(CH3)-O-CH2CH(CH3)2 -OH -O-CO-(CH2)2CH(CH3)2 ＝O -CH(CH3)-O-(CH2)2CH(CH3)2 -OH -O-CO-(CH2)3CH(CH3)2 ＝O -CH(CH3)-O-(CH2)3CH(CH3)2 -OH -O-CO-(CH2)4CH(CH3)2 ＝O -CH(CH3)-O-(CH2)4CH(CH3)2 -OH -O-CO-(CH2)5CH(CH3)2 ＝O -CH(CH3)-O-(CH2)5CH(CH3)2 -OH -O-CO-(CH2)6CH(CH3)2 ＝O -CH(CH3)-O-(CH2)6CH(CH3)2 -OH -O-CO-(CH2)7CH(CH3)2 ＝O -CH(CH3)-O-(CH2)7CH(CH3)2 -OH -O-CO-(CH2)8CH(CH3)2 ＝O -CH(CH3)-O-(CH2)8CH(CH3)2 -OH -O-CO-(CH2)9CH(CH3)2 ＝O -CH(CH3)-O-(CH2)9CH(CH3)2 -OH -O-CO-(CH2)10CH(CH3)2 ＝O -CH(CH3)-O-(CH2)10CH(CH3)2 -OH -CH(CH3)-CH3 -OH -CH(CH3)-O-CH3 -OH -CH(CH3)-CH2CH3 -OH -CH(CH3)-O-CH2CH3 -OH -CH(CH3)-(CH2)2CH3 -OH -CH(CH3)-O-(CH2)2CH3 -OH -CH(CH3)-(CH2)3CH3 -OH -CH(CH3)-O-(CH2)3CH3 -OH -CH(CH3)-(CH2)4CH3 -OH -CH(CH3)-O-(CH2)4CH3 -OH -CH(CH3)-(CH2)5CH3 -OH -CH(CH3)-O-(CH2)5CH3 -OH -CH(CH3)-(CH2)6CH3 -OH -CH(CH3)-O-(CH2)6CH3 -OH -CH(CH3)-(CH2)7CH3 -OH -CH(CH3)-O-(CH2)7CH3 -OH -CH(CH3)-(CH2)8CH3 -OH -CH(CH3)-O-(CH2)8CH3 -OH -CH(CH3)-(CH2)9CH3 -OH -CH(CH3)-O-(CH2)9CH3 -OH -CH(CH3)-(CH2)10CH3 -OH -CH(CH3)-O-(CH2)10CH3 -OH -CH(CH3)-(CH2)11CH3 -OH -CH(CH3)-O-(CH2)11CH3 -OH -CH(CH3)-(CH2)12CH3 -OH -CH(CH3)-O-(CH2)12CH3 -OH -CH(CH3)-CH(CH3)2 -OH -CH(CH3)-O-CH(CH3)2 -OH -CH(CH3)-CH2CH(CH3)2 -OH -CH(CH3)-O-CH2CH(CH3)2 -OH -CH(CH3)-(CH2)2CH(CH3)2 -OH -CH(CH3)-O-(CH2)2CH(CH3)2 -OH -CH(CH3)-(CH2)3CH(CH3)2 -OH -CH(CH3)-O-(CH2)3CH(CH3)2 -OH -CH(CH3)-(CH2)4CH(CH3)2 -OH -CH(CH3)-O-(CH2)4CH(CH3)2 -OH -CH(CH3)-(CH2)5CH(CH3)2 -OH -CH(CH3)-O-(CH2)5CH(CH3)2 -OH -CH(CH3)-(CH2)6CH(CH3)2 -OH -CH(CH3)-O-(CH2)6CH(CH3)2 -OH -CH(CH3)-(CH2)7CH(CH3)2 -OH -CH(CH3)-O-(CH2)7CH(CH3)2 -OH -CH(CH3)-(CH2)8CH(CH3)2 -OH -CH(CH3)-O-(CH2)8CH(CH3)2 -OH -CH(CH3)-(CH2)9CH(CH3)2 -OH -CH(CH3)-O-(CH2)9CH(CH3)2 -OH -CH(CH3)-(CH2)10CH(CH3)2 -OH -CH(CH3)-O-(CH2)10CH(CH3)2 ＝O -O-CO-C6H5 -OH -O-CO-C6H5 ＝O -O-CO-CH2C6H5 -OH -O-CO-CH2C6H5 ＝O -CH(CH2CH3)-CH2CH3 -OH -CH(CH2CH3)-CH2CH3 ＝O -CH(CH2CH3)-O-CH2CH3 -OH -CH(CH2CH3)-O-CH2CH3 ＝O -CH(CH3)-C6H5 -OH -CH(CH3)-C6H5 ＝O -CH(CH3)-CH2C6H5 -OH -CH(CH3)-CH2C6H5 ＝O -CH(CH3)-CH2CH2C6H5 -OH -CH(CH3)-CH2CH2C6H5 ＝O -(CH2)5CH3 -OH -(CH2)5CH3 ＝O -(CH2)5CH3 -OH -(CH2)5CH3 ＝O -CH2-O-CH2CH3 -OH -CH(CH2CH3)-O-CH2CH3 ＝O -CH(CH3)-CH=CHCH2CH(CH3)2 -OH -CH(CH3)-O-(CH2)10CH(CH3)2 ──────────────────────────────────── これらのうち、特に好ましい化合物としては、X が＝O
でありR が-CH(CH3)-(CH2)3CH(CH3)2 である化合物、X
が＝O でありR が-CH(CH3)-O-(CH2)2CH(CH3)2である化
合物、およびX が＝O でありR が-O-CO-(CH2)8CH3 であ
る化合物を挙げることができる。[Table 1] XRXR ──────────────────────────────────── ＝ O -O-CO-CH 3 = O -CH (CH 3) -CH 3 = O -O-CO-CH 2 CH 3 = O -CH (CH 3) -CH 2 CH 3 = O -O-CO- (CH 2) 2 CH 3 = O -CH (CH 3) - ( CH 2) 2 CH 3 = O -O-CO- (CH 2) 3 CH 3 = O -CH (CH 3) - (CH 2) 3 CH 3 = O -O- CO- (CH 2) 4 CH 3 = O -CH (CH 3) - (CH 2) 4 CH 3 = O -O-CO- (CH 2) 5 CH 3 = O -CH (CH 3) - (CH 2 ) 5 CH 3 = O -O-CO- (CH 2 ) 6 CH 3 = O -CH (CH 3 )-(CH 2 ) 6 CH 3 = O -O-CO- (CH 2 ) 7 CH 3 = O -CH (CH 3) - ( CH 2) 7 CH 3 = O -O-CO- (CH 2) 8 CH 3 = O -CH (CH 3) - (CH 2) 8 CH 3 = O -O- CO- (CH 2) 9 CH 3 = O -CH (CH 3) - (CH 2) 9 CH 3 = O -O-CO- (CH 2) 10 CH 3 = O -CH (CH 3) - (CH 2 ) 10 CH 3 = O -O-CO- (CH 2 ) 11 CH 3 = O -CH (CH 3 )-(CH 2 ) 11 CH 3 = O -O-CO- (CH 2 ) 12 CH 3 = O -CH (CH 3) - ( CH 2) 12 CH 3 = O -O-CO-CH (CH 3) 2 = O -CH (CH 3) -CH (CH 3) 2 = O -O-CO- CH 2 CH (CH 3 ) 2 ＝ O -CH (CH 3 ) -CH 2 CH (CH 3 ) 2 ＝ O -O-CO- (CH 2 ) 2 CH (CH 3 ) 2 ＝ O -CH (CH 3 )-(CH 2 ) 2 CH (CH 3 ) 2 ＝ O -O-CO- (CH 2 ) 3 CH (CH 3 ) 2 ＝ O -CH (CH 3 )-(CH 2 ) 3 CH (CH 3 ) 2 = O -O-CO- (CH 2 ) 4 CH (CH 3 ) 2 = O -CH (CH 3 )-(CH 2 ) 4 CH (CH 3 ) 2 = O -O-CO- (CH 2 ) 5 CH (CH 3 ) 2 ＝ O -CH (CH 3 )-(CH 2 ) 5 CH (CH 3 ) 2 ＝ O -O-CO- (CH 2 ) 6 CH (CH 3 ) 2 ＝ O -CH (CH 3) - (CH 2 ) 6 CH (CH 3) 2 = O -O-CO- (CH 2) 7 CH (CH 3) 2 = O -CH (CH 3) - (CH 2) 7 CH ( CH 3) 2 = O -O- CO- (CH 2) 8 CH (CH 3) 2 = O -CH (CH 3) - (CH 2) 8 CH (CH 3) 2 = O -O-CO- ( CH 2 ) 9 CH (CH 3 ) 2 ＝ O -CH (CH 3 )-(CH 2 ) 9 CH (CH 3 ) 2 ＝ O -O-CO- (CH 2 ) 10 CH (CH 3 ) 2 ＝ O -CH (CH 3) - (CH 2) 10 CH (CH 3) 2 -OH -O-CO-CH 3 = O -CH (CH 3) -O-CH 3 -OH -O-CO-CH 2 CH 3 = O -CH (CH 3) -O-CH 2 CH 3 -OH -O-CO- (CH 2) 2 CH 3 = O -CH (CH 3) -O- (CH 2) 2 CH 3 -OH -O-CO- (CH 2) 3 CH 3 = O -CH (CH 3) -O- (CH 2) 3 CH 3 -OH -O-CO- (CH 2) 4 CH 3 = O -CH (CH 3 ) -O- (CH 2 ) 4 CH 3 -OH -O-CO- (CH 2 ) 5 CH 3 = O -CH (CH 3 ) -O- (CH 2 ) 5 CH 3 -OH -O-CO - (CH 2) 6 CH 3 = O -CH (CH 3) -O- (CH 2) 6 CH 3 -OH -O-CO- (CH 2) 7 CH 3 O -CH (CH 3) -O- ( CH 2) 7 CH 3 -OH -O-CO- (CH 2) 8 CH 3 = O -CH (CH 3) -O- (CH 2) 8 CH 3 - OH -O-CO- (CH 2) 9 CH 3 = O -CH (CH 3) -O- (CH 2) 9 CH 3 -OH -O-CO- (CH 2) 10 CH 3 = O -CH ( CH 3 ) -O- (CH 2 ) 10 CH 3 -OH -O-CO- (CH 2 ) 11 CH 3 = O -CH (CH 3 ) -O- (CH 2 ) 11 CH 3 -OH -O- CO- (CH 2) 12 CH 3 = O -CH (CH 3) -O- (CH 2) 12 CH 3 -OH -O-CO-CH (CH 3) 2 = O -CH (CH 3) -O -CH (CH 3) 2 -OH -O -CO-CH 2 CH (CH 3) 2 = O -CH (CH 3) -O-CH 2 CH (CH 3) 2 -OH -O-CO- (CH 2 ) 2 CH (CH 3 ) 2 = O-CH (CH 3 ) -O- (CH 2 ) 2 CH (CH 3 ) 2 -OH -O-CO- (CH 2 ) 3 CH (CH 3 ) 2 = O -CH (CH 3) -O- ( CH 2) 3 CH (CH 3) 2 -OH -O-CO- (CH 2) 4 CH (CH 3) 2 = O -CH (CH 3) -O- (CH 2 ) 4 CH (CH 3 ) 2 -OH -O-CO- (CH 2 ) 5 CH (CH 3 ) 2 = O -CH (CH 3 ) -O- (CH 2 ) 5 CH (CH 3 ) 2 -OH -O-CO- (CH 2 ) 6 CH (CH 3) 2 = O -CH (CH 3) -O- (CH 2) 6 CH (CH 3) 2 -OH -O-CO- (CH 2 ) 7 CH (CH 3 ) 2 = O -CH (CH 3 ) -O- (CH 2 ) 7 CH (CH 3 ) 2 -OH -O-CO- (CH 2 ) 8 CH (CH 3 ) 2 = O -CH (CH 3) -O- ( CH 2) 8 CH (CH 3) 2 -OH -O-CO- (CH 2) 9 CH (CH 3) 2 = O -CH (CH 3) -O- (CH 2 ) 9 CH (CH 3 ) 2- OH -O-CO- (CH 2 ) 10 CH (CH 3 ) 2 = O -CH (CH 3 ) -O- (CH 2 ) 10 CH (CH 3 ) 2- OH -CH (CH 3 ) -CH 3 -OH -CH (CH 3 ) -O-CH 3 -OH -CH (CH 3 ) -CH 2 CH 3 -OH -CH (CH 3 ) -O-CH 2 CH 3 -OH -CH (CH 3 )-(CH 2 ) 2 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 2 CH 3 -OH -CH (CH 3 )-(CH 2 ) 3 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 3 CH 3 -OH -CH (CH 3 )-(CH 2 ) 4 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 4 CH 3 -OH -CH (CH 3) - (CH 2) 5 CH 3 -OH -CH (CH 3) -O- (CH 2) 5 CH 3 -OH -CH (CH 3) - (CH 2) 6 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 6 CH 3 -OH -CH (CH 3 )-(CH 2 ) 7 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 7 CH 3 -OH -CH (CH 3 )-(CH 2 ) 8 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 8 CH 3 -OH -CH (CH 3 )-(CH 2 ) 9 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 9 CH 3 -OH -CH (CH 3 )-(CH 2 ) 10 CH 3 -OH -CH (CH 3 ) -O- ( CH 2 ) 10 CH 3 -OH -CH (CH 3 )-(CH 2 ) 11 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 11 CH 3 -OH -CH (CH 3 )-( CH 2 ) 12 CH 3 -OH -CH (CH 3 ) -O- (CH 2 ) 12 CH 3 -OH -CH (CH 3 ) -CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- CH (CH 3 ) 2 -OH -CH (CH 3 ) -CH 2 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O-CH 2 CH (CH 3 ) 2 -OH- CH (CH 3 )-(CH 2 ) 2 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 2 CH (CH 3 ) 2 -OH -CH (CH 3 )-(CH 2 ) 3 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 3 CH (CH 3 ) 2 -OH -CH (CH 3 )-(CH 2 ) 4 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 4 CH (CH 3 ) 2 -OH -CH (CH 3 )-(CH 2 ) 5 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 5 CH (CH 3 ) 2 -OH -CH (CH 3 )-(CH 2 ) 6 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 6 CH (CH 3 ) 2 -OH -CH (CH 3 )-(CH 2 ) 7 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 7 CH (CH 3 ) 2- OH -CH (CH 3 )-(CH 2 ) 8 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 8 CH (CH 3 ) 2 -OH -CH (CH 3 )- (CH 2 ) 9 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 9 CH (CH 3 ) 2 -OH -CH (CH 3 )-(CH 2 ) 10 CH (CH 3 ) 2 -OH -CH (CH 3 ) -O- (CH 2 ) 10 CH (CH 3 ) 2 = O -O-CO-C 6 H 5 -OH -O-CO-C 6 H 5 = O- O-CO-CH 2 C 6 H 5 -OH -O-CO-CH 2 C 6 H 5 = O -CH (CH 2 CH 3 ) -CH 2 CH 3 -OH -CH (CH 2 CH 3 ) -CH 2 CH 3 = O -CH (CH 2 CH 3 ) -O-CH 2 CH 3 -OH -CH (CH 2 CH 3 ) -O-CH 2 CH 3 = O -CH (CH 3 ) -C 6 H 5 -OH -CH (CH 3) -C 6 H 5 = O -CH (CH 3) -CH 2 C 6 H 5 -OH -CH (CH 3) -CH 2 C 6 H 5 = O -CH (CH 3) -CH 2 CH 2 C 6 H 5 -OH -CH (CH 3) -CH 2 CH 2 C 6 H 5 = O - (CH 2) 5 CH 3 -OH - (CH 2) 5 CH 3 = O-(CH 2 ) 5 CH 3 -OH-(CH 2 ) 5 CH 3 = O -CH 2 -O-CH 2 CH 3 -OH -CH (CH 2 CH 3 ) -O-CH 2 CH 3 = O -CH (CH 3) -CH = CHCH 2 CH (CH 3) 2 -OH -CH (CH 3) -O- (CH 2) 10 CH (CH 3) 2 ──────── ──────────────────────────── Among these, X is ═O
In it R is -CH (CH 3) - (CH 2) 3 CH (CH 3) compound is 2, X
There = O and and wherein R is -CH (CH 3) -O- (CH 2) 2 CH (CH 3) 2 , compound, and X is = is O R is -O-CO- (CH 2) 8 Mention may be made of compounds which are CH 3 .

【０００９】これらの化合物の一部は新規化合物であ
る。これらは、上記の式中、X が＝Oを示し、R が-O-CO
-R1または-CHR2-R3を示す化合物である。R1は直鎖また
は分枝したアルキル基、直鎖または分枝したアルケニル
基、直鎖または分枝したアラルキル基、あるいは置換ま
たは非置換フェニル基であり、R2は水素原子、あるいは
直鎖または分枝した低級アルキル基であり、R3は直鎖ま
たは分枝したアルキル基、直鎖または分枝したアルケニ
ル基、直鎖または分枝したアルコキシ基、直鎖または分
枝したアルケニルオキシ基、直鎖または分枝したアラル
キル基、あるいは置換または非置換フェニル基である。
ただし、R は-CH(CH3)(CH2)3CH(CH3)2であることはな
い。これらの化合物は、例えば、本明細書の実施例に記
載された方法により製造することができる。Some of these compounds are new compounds. In these formulas, X represents ═O and R represents —O—CO.
A compound showing -R 1 or -CHR 2 -R 3 . R 1 is a linear or branched alkyl group, a linear or branched alkenyl group, a linear or branched aralkyl group, or a substituted or unsubstituted phenyl group, R 2 is a hydrogen atom, or a linear or R 3 is a branched lower alkyl group, R 3 is a linear or branched alkyl group, a linear or branched alkenyl group, a linear or branched alkoxy group, a linear or branched alkenyloxy group, a direct It is a chain or branched aralkyl group, or a substituted or unsubstituted phenyl group.
Here, R is -CH (CH 3) (CH 2 ) 3 CH (CH 3) does not is 2. These compounds can be produced, for example, by the method described in the examples of the present specification.

【００１０】公知の化合物は、公知文献に記載された方
法により当業者に容易に製造される。例えば３β，５α
−ジヒドロキシコレスタン−６−オン (YS-64)等は、フ
ィーザーらの方法(Fieser, L.F., Rajagopalan, S., J.
Am. Chem. Soc., 1949, 71,3938-3941) により製造す
ることができる。本発明の阻害剤は、リガンド依存的に
細胞質内から核内へと移行する性質を有する発がんプロ
モーター結合蛋白CN-TPBP(Cytosolic-Nuclear Tumor Pr
omoter-Specific Binding Protein)に対して強い親和性
を示し、TPA 等の発がんプロモータのCN-TPBP に対する
結合を拮抗的に阻害する。加えて、本発明の阻害剤は、
ホルボールエステルやテレオシジンのような蛋白質リン
酸化酵素活性化作用を有しないので、発がんプロモータ
ーの作用を抑制することができ、発がんプロモーターの
作用抑制剤あるいは発がん抑制剤として有用である。発
がんプロモーターの作用機序の研究用試薬または発がん
プロモーターのスクリーニング用試薬等の生化学用試薬
として、あるいは臨床検査用試薬として有用である。Known compounds are easily prepared by those skilled in the art by the methods described in the known literature. For example, 3β, 5α
-Dihydroxycholestane-6-one (YS-64) and the like are described by Fieser et al. (Fieser, LF, Rajagopalan, S., J.
Am. Chem. Soc., 1949, 71, 3938-3941). The inhibitor of the present invention is a carcinogenic promoter-binding protein CN-TPBP (Cytosolic-Nuclear Tumor Prr) having a property of migrating from the cytoplasm to the nucleus in a ligand-dependent manner.
It has a strong affinity for omoter-specific binding proteins) and competitively inhibits the binding of carcinogenic promoters such as TPA to CN-TPBP. In addition, the inhibitors of the present invention are
Since it does not have a protein phosphatase activating effect such as phorbol ester and tereosidine, it can suppress the action of a carcinogenic promoter, and is useful as an inhibitor of carcinogenic promoter action or a carcinogenic inhibitor. It is useful as a biochemical reagent such as a reagent for studying the mechanism of action of a carcinogenic promoter or a reagent for screening a carcinogenic promoter, or as a reagent for clinical examination.

【００１１】本発明の阻害剤を、ヒト等の哺乳類に対し
て発がん抑制剤として用いる場合には、式（Ｉ）で示さ
れる上記の化合物を有効成分として含む医薬組成物とし
て投与すればよい。このような医薬用組成物は、経口的
あるいは非経口的に患者に投与すればよく、例えば、錠
剤、カプセル剤、散剤、細粒剤、顆粒剤、液剤、及びシ
ロップ剤等等の経口投与用医薬組成物、あるいは注射
剤、坐剤、吸入剤、点眼剤、点鼻剤、軟膏剤、及び貼付
剤等の非経口投与用医薬組成物として投与すればよい。
これらの医薬組成物は、薬理学的、製剤学的に許容しう
る添加物を加えて製造してもよい。薬理学的、製剤学的
に許容しうる添加物の例として、例えば、賦形剤、崩壊
剤ないし崩壊補助剤、結合剤、滑沢剤、コーティング
剤、色素、希釈剤、基剤、溶解剤ないし溶解補助剤、等
張化剤、ｐＨ調節剤、安定化剤、噴射剤、及び粘着剤等
を挙げることができ、これらは目的に応じて適宜当業者
により選択される。When the inhibitor of the present invention is used as a carcinogenesis inhibitor in mammals such as humans, it may be administered as a pharmaceutical composition containing the above compound represented by the formula (I) as an active ingredient. Such a pharmaceutical composition may be orally or parenterally administered to a patient, for example, for oral administration of tablets, capsules, powders, fine granules, granules, liquids, syrups and the like. It may be administered as a pharmaceutical composition or a pharmaceutical composition for parenteral administration such as injection, suppository, inhalation, eye drop, nasal drop, ointment, and patch.
These pharmaceutical compositions may be manufactured by adding pharmacologically and pharmaceutically acceptable additives. Examples of pharmacologically and pharmaceutically acceptable additives include, for example, excipients, disintegrants or disintegration aids, binders, lubricants, coating agents, dyes, diluents, bases, solubilizers. Or a solubilizer, a tonicity agent, a pH adjuster, a stabilizer, a propellant, an adhesive and the like, which are appropriately selected by those skilled in the art depending on the purpose.

【００１２】例えば、経口投与、あるいは経皮又は経粘
膜投与に適する医薬用組成物には、ブドウ糖、乳糖、D-
マンニトール、デンプン、又は結晶セルロース等の賦形
剤；カルボキシメチルセルロース、デンプン、又はカル
ボキシメチルセルロースカルシウム等の崩壊剤又は崩壊
補助剤；ヒドロキシプロピルセルロース、ヒドロキシプ
ロピルメチルセルロース、ポリビニルピロリドン、又は
ゼラチン等の結合剤；ステアリン酸マグネシウム又はタ
ルク等の滑沢剤；ヒドロキシプロピルメチルセルロー
ス、白糖、ポリエチレングリコール又は酸化チタン等の
コーティング剤；ワセリン、流動パラフィン、ポリエチ
レングリコール、ゼラチン、カオリン、グリセリン、精
製水、又はハードファット等の基剤；フロン，ジエチル
エーテル、又は圧縮ガス等の噴射剤；ポリアクリル酸ナ
トリウム、ポリビニルアルコール、メチルセルロース、
ポリイソブチレン、ポリブテン等の粘着剤；木綿布又は
プラスチックシート等の基布等の製剤用添加物を添加す
ることができる。注射用に適する医薬用組成物には、注
射用蒸留水、生理食塩水、プロピレングリコール等の水
性あるいは用時溶解型注射剤を構成しうる溶解剤又は溶
解補助剤；ブドウ糖、塩化ナトリウム、D-マンニトー
ル、グリセリン等の等張化剤；無機酸、有機酸、無機塩
基又は有機塩基等のpH調節剤等の製剤用添加物を添加し
てもよい。発がんの予防を目的として上記の医薬用組成
物を投与する場合の投与量は、目的に応じて適宜選択す
ればよいが、例えば、成人一日あたり有効成分として0.
1 〜10 mgを投与すればよい。For example, pharmaceutical compositions suitable for oral administration, transdermal or transmucosal administration include glucose, lactose, D-
Excipients such as mannitol, starch, or crystalline cellulose; disintegrating agents or disintegrating agents such as carboxymethylcellulose, starch, or carboxymethylcellulose calcium; binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, or gelatin; stearin Lubricants such as magnesium acid or talc; Coating agents such as hydroxypropylmethylcellulose, sucrose, polyethylene glycol or titanium oxide; Vaseline, liquid paraffin, polyethylene glycol, gelatin, kaolin, glycerin, purified water, or bases such as hard fat Propellants such as CFCs, diethyl ether, or compressed gas; sodium polyacrylate, polyvinyl alcohol, methyl cellulose,
Adhesives such as polyisobutylene and polybutene; additives for preparations such as cotton cloth or base cloth such as plastic sheet can be added. Pharmaceutical compositions suitable for injection include distilled water for injection, physiological saline, solubilizers or solubilizers that can constitute aqueous or injection-soluble injections such as propylene glycol; glucose, sodium chloride, D- Tonicity agents such as mannitol and glycerin; pharmaceutical additives such as pH adjusting agents such as inorganic acids, organic acids, inorganic bases or organic bases may be added. The dose in the case of administering the above-mentioned pharmaceutical composition for the purpose of preventing carcinogenesis may be appropriately selected depending on the purpose, for example, 0 as an active ingredient per day for an adult.
1 to 10 mg may be given.

【００１３】[0013]

【実施例】以下に本発明を実施例によりさらに具体的に
説明するが、本発明はこれらの実施例に限定されること
はない。 例１：３β，５α−ジヒドロキシ−２３，２４−ビスノ
ルコラン−６−オン（ＹＳ−１４９） スチグマステリルアセテートをメタクロル過安息香酸で
選択的に酸化した後、触媒量の過塩素酸の存在下に加水
分解して３β−アセトキシ−スチグマスト−２２−エン
−５α，６β−ジオールを得た。アルミニウムオキサイ
ドの存在下にこの化合物をピリジニウムクロロクロメー
トで酸化し、さらに６位ケトンをエチレンジオキシ基で
保護して３β−アセトキシ−６，６−エチレンジオキシ
スチグマスト−２２−エン−５α−オールを得た。この
化合物をメタノール−ジクロロメタン−ピリジン中でオ
ゾン分解して、ビスノルコラン−２２−アールを得た。EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these examples. Example 1: 3β, 5α-Dihydroxy-23,24-bisnorcholan-6-one (YS-149) Stigmasteryl acetate was selectively oxidized with metachloroperbenzoic acid and then in the presence of catalytic amount of perchloric acid. To give 3β-acetoxy-stigmast-22-ene-5α, 6β-diol. This compound was oxidized with pyridinium chlorochromate in the presence of aluminum oxide, and the 6-position ketone was protected with an ethylenedioxy group to give 3β-acetoxy-6,6-ethylenedioxystigmast-22-ene-5α-. Got all. This compound was subjected to ozonolysis in methanol-dichloromethane-pyridine to obtain bisnorcholan-22-al.

【００１４】ビスノルコラン−２２−アールをエチレン
グリコール中でヒドラジン水和物と水酸化カリウムによ
り処理して６位ケトンの脱保護を行い、３β，５α−ジ
ヒドロキシ−２３，２４−ビスノルコラン−６−オンを
得た。 YS-149：無色針状晶 m.p. 149-150 ℃（エタノール／n-
ヘキサン） Anal. (C22H36O3: R=-CH(CH3)2)1 H-NMR (CDCl3) 0.64(s,3H,18-CH3), 0.81(s,3H,19-CH
3), 0.84(d,3H, J=6.6Hz, 22-CH3), 0.92(d,3H,J=6.6H
z,21-CH3), 2.01(bd,1H), 2.13(dd,1H,J=12.8 & 4.8Hz,
7-beta-H), 2.70 (t,1H,J=12.8Hz,7-alpha-H), 3.97(m,
1H,3-alpha-H)Bisnorcholan-22-al is treated with hydrazine hydrate and potassium hydroxide in ethylene glycol to deprotect the 6-position ketone to give 3β, 5α-dihydroxy-23,24-bisnorcholan-6-one. Obtained. YS-149: colorless needle crystals mp 149-150 ℃ (Ethanol / n-
Hexane) Anal. (C 22 H 36 O 3 : R = -CH (CH 3 ) 2 ) 1 H-NMR (CDCl 3 ) 0.64 (s, 3H, 18-CH 3 ), 0.81 (s, 3H, 19- CH
3 ), 0.84 (d, 3H, J = 6.6Hz, 22-CH 3 ), 0.92 (d, 3H, J = 6.6H
z, 21-CH 3 ), 2.01 (bd, 1H), 2.13 (dd, 1H, J = 12.8 & 4.8Hz,
7-beta-H), 2.70 (t, 1H, J = 12.8Hz, 7-alpha-H), 3.97 (m,
1H, 3-alpha-H)

【００１５】例２：３β，５α−ジヒドロキシ−２３，
２４−ビスノルコラン−６−オン（ＹＳ−１４９）の側
鎖伸長体 ビスノルコラン−２２−アールをテトラヒドロフラン中
で適当なホスホニウムイリドにより処理してシス体およ
びトランス体の混合物として２２−不飽和化合物を得
た。例１に記載された方法により６位ケトンの脱保護を
行い、さらに２２位の二重結合を接触還元して３β，５
α−ジヒドロキシ−２３，２４−ビスノルコラン−６−
オン（ＹＳ−１４９）の側鎖伸長体を得た。 YS-151： m.p. 245-246.5 ℃（エタノール／n-ヘキサ
ン） Anal. (C23H38O3: X=O, R=-CH(CH3)CH2CH3) YS-152： m.p. 248-249.5 ℃（エタノール／n-ヘキサ
ン） Anal. (C24H40O3: X=O, R=-CH(CH3)CH2CH2CH3) YS-153： m.p. 239-241.5 ℃（エタノール／n-ヘキサ
ン） Anal. (C25H42O3: X=O, R=-CH(CH3)CH2CH2CH2CH3) YS-154： m.p. 226-229 ℃ （酢酸エチル） Anal. (C26H44O3: X=O, R=-CH(CH3)CH2CH2CH2CH2CH3) YS-155： m.p. 217-220 ℃ （酢酸エチル） Anal. (C27H46O3: X=O, R=-CH(CH3)CH2CH2CH2CH2CH2C
H3) YS-156： m.p. 210-212 ℃ （酢酸エチル） Anal. (C28H48O3: X=O, R=-CH(CH3)CH2CH2CH2CH2CH2CH2
CH3) YS-157： m.p. 212-214 ℃ （酢酸エチル） Anal. (C29H50O3: X=O, R=-CH(CH3)CH2CH2CH2CH2CH2CH2
CH2CH3) YS-161： m.p. 241-243.5 ℃ (酢酸エチル） Anal. (C29H42O3: X=O, R=-CH(CH3)CH2CH2C6H5)Example 2: 3β, 5α-dihydroxy-23,3
Side Chain Extension of 24-Bisnorcholan-6-one (YS-149) Bisnorcholan-22-al was treated with an appropriate phosphonium ylide in tetrahydrofuran to give a 22-unsaturated compound as a mixture of cis and trans isomers. . The 6-position ketone was deprotected by the method described in Example 1 and the double bond at the 22-position was catalytically reduced to give 3β, 5.
α-dihydroxy-23,24-bisnorcholan-6-
A side chain extension product of ON (YS-149) was obtained. YS-151: mp 245-246.5 ℃ (Ethanol / n-hexane) Anal. (C 23 H 38 O 3 : X = O, R = -CH (CH 3 ) CH 2 CH 3 ) YS-152: mp 248- 249.5 ℃ (Ethanol / n-hexane) Anal. (C 24 H 40 O 3 : X = O, R = -CH (CH 3 ) CH 2 CH 2 CH 3 ) YS-153: mp 239-241.5 ℃ (Ethanol / n-Hexane) Anal. (C 25 H 42 O 3 : X = O, R = -CH (CH 3 ) CH 2 CH 2 CH 2 CH 3 ) YS-154: mp 226-229 ℃ (Ethyl acetate) Anal. (C 26 H 44 O 3 : X = O, R = -CH (CH 3 ) CH 2 CH 2 CH 2 CH 2 CH 3 ) YS-155: mp 217-220 ℃ (Ethyl acetate) Anal. (C 27 H 46 O 3 : X = O, R = -CH (CH 3 ) CH 2 CH 2 CH 2 CH 2 CH 2 C
H 3 ) YS-156: mp 210-212 ℃ (Ethyl acetate) Anal. (C 28 H 48 O 3 : X = O, R = -CH (CH 3 ) CH 2 CH 2 CH 2 CH 2 CH 2 CH 2
CH 3 ) YS-157: mp 212-214 ℃ (Ethyl acetate) Anal. (C 29 H 50 O 3 : X = O, R = -CH (CH 3 ) CH 2 CH 2 CH 2 CH 2 CH 2 CH 2
CH 2 CH 3 ) YS-161: mp 241-243.5 ℃ (Ethyl acetate) Anal. (C 29 H 42 O 3 : X = O, R = -CH (CH 3 ) CH 2 CH 2 C 6 H 5 )

【００１６】例３：３ｂ，５ａ−ジヒドロキシコレスト
−２２Ｅ−エン−６−オン（ＹＳ−１２６） ビスノルコラン−２２−アールをテトラヒドロフラン中
でイソアミルトリフェニルホスホニウムイリドで処理
し、トランス−２２−エン体を得た。６−ケト基と３ベ
ータ水酸基の脱保護を行い、目的化合物を得た。 YS-126： m.p. 235-238 ℃（酢酸エチル） Anal. (C27H44O3: R=-CH(CH3)CH=CHCH2CH(CH3)2)1 H-NMR (CDCl3) 0.68(s,3H,18-CH3), 0.81(s,3H,19-CH
3), 0.88, 0.89(d,2×3H, J=6.6Hz, 26-,27-CH3), 0.95
(d,3H,J=6.6Hz,21-CH3), 2.01(bd,1H), 2.13(dd,1H,J=1
2.7 & 4.7Hz,7-beta-H), 2.41(m,1H,20-H), 2.71 (t,1
H,J=12.7Hz,7-alpha-H), 3.97(m,1H,3-alpha-H), 5.18
(m,2H,22-,23H)Example 3: 3b, 5a-Dihydroxycholest-22E-en-6-one (YS-126) Bisnorcholan-22-al was treated with isoamyltriphenylphosphonium ylide in tetrahydrofuran to give the trans-22-ene form. Got The 6-keto group and 3 beta hydroxyl group were deprotected to obtain the target compound. YS-126: mp 235-238 ℃ (Ethyl acetate) Anal. (C 27 H 44 O 3 : R = -CH (CH 3 ) CH = CHCH 2 CH (CH 3 ) 2 ) 1 H-NMR (CDCl 3 ). 0.68 (s, 3H, 18-CH 3 ), 0.81 (s, 3H, 19-CH
3 ), 0.88, 0.89 (d, 2 × 3H, J = 6.6Hz, 26-, 27-CH 3 ), 0.95
(d, 3H, J = 6.6Hz, 21-CH 3 ), 2.01 (bd, 1H), 2.13 (dd, 1H, J = 1
2.7 & 4.7Hz, 7-beta-H), 2.41 (m, 1H, 20-H), 2.71 (t, 1
H, J = 12.7Hz, 7-alpha-H), 3.97 (m, 1H, 3-alpha-H), 5.18
(m, 2H, 22-, 23H)

【００１７】例４ 5.００ｇのプレグネノロンをジメチルホルムアミド１５
mlとテトラヒドロフラン１５mlの混合物に溶解し、イミ
ダゾール4.３９５ｇ（３当量）を加えた。氷冷下に、3.
６８５ｇのターシャリーブチルジメチルシリルクロライ
ド（約1.５当量）を加えて１０時間攪拌した。３０mlの
水を加えて溶媒を留去し、ジクロルメタンで抽出して、
水洗、脱水後に溶媒を留去した。残渣をシリカゲルカラ
ムクロマトグラフィー（酢酸エチル：n-ヘキサン＝１
０：１）により精製し、6.５７ｇの３位水酸基のシリル
化保護体を得た（収率９6.５％）。酢酸エチルより再結
晶して無色柱状晶を得た（m.p. 164.5-165℃) 。Example 4 5.00 g of pregnenolone was added to dimethylformamide 15
It was dissolved in a mixture of 15 ml of tetrahydrofuran and 15 ml of tetrahydrofuran, and 4.395 g (3 equivalents) of imidazole was added. Under ice cooling, 3.
685 g of tert-butyldimethylsilyl chloride (about 1.5 equivalents) was added and stirred for 10 hours. 30 ml of water was added, the solvent was distilled off, and the mixture was extracted with dichloromethane,
After washing with water and dehydration, the solvent was distilled off. The residue was subjected to silica gel column chromatography (ethyl acetate: n-hexane = 1)
Purification by 0: 1) gave 6.57 g of a protected product of silylated 3-hydroxyl group (yield: 96.5%). Recrystallization from ethyl acetate gave colorless columnar crystals (mp 164.5-165 ° C).

【００１８】上記のシリル体3.３５ｇをエタノール５０
mlとテトラヒドロフラン５０mlの混合物に溶解し、ナト
リウムボロハイドライド0.９０ｇを氷冷下に加え、室温
で５時間攪拌した。５％酢酸を溶液に加えて溶媒を留去
し、水を加えてジクロルメタンにより抽出した。水洗、
脱水後に溶媒を留去し、シリカゲルカラムクロマトグラ
フィー（酢酸エチル：n-ヘキサン＝７：１）により精製
し、２０位カルボニル基が水酸基に還元された化合物2.
４４ｇを得た（収率７2.４％）。メタノールより再結晶
して無色針状晶を得た（m.p. 151℃) 。ナトリウムハイ
ドライド 138.8 mg をn-ヘキサン(1ml×3)で洗浄してキ
シレン１mlに懸濁し、上記の化合物 606.7 mg をキシレ
ン４mlに溶解して加え、イソペンチルクロライド0.８７
mlを加えて１７時間還流した。１０％クエン酸と水を加
えてジクロルメタンにより抽出し、水洗、脱水した後、
溶媒を留去した。残渣をシリカゲルカラムクロマトグラ
フィー（n-ヘキサン：ジクロルメタン＝３：１）により
精製して、２０位にイソペンチルオキシ基が導入された
化合物 490.8 mgを得た（収率６9.７％）。メタノール
より再結晶して無色針状晶を得た（m.p. 82 ℃) 。1 H-NMR (400MHz/CDCl3) 0.05(s,6H,TBDMS Me), 0.69(s,
3H,18-CH3), 0.88(s,9H,TBDMS t-Bu), 0.90(d,6H,J=6.5
Hz,4'-CH3), 1.00(s,3H,19-CH3), 1.06(d,3H,J=6.0Hz,2
1-CH3), 3.22(dt,1H,J=7.9Hz,1'-H), 3.25(m,1H,20-H),
3.47 (m,1H,3-H), 3.57(dt,1H,J=7.9Hz,1'-H), 5.31(d
d,1H,J=5.0Hz,6-H) 上記の化合物 547.0 mg をアセトン２３mgに溶解し、過
塩素酸0.０５ml、水0.０５ml、およびアセトン２mlの混
合物を氷冷下で加えた。室温で３時間攪拌した後、飽和
重曹水６mlを加えてアセトンを留去し、水を加えてジク
ロルメタン（３０ml×３）で抽出した。水洗、脱水後に
溶媒を留去し、残渣をシリカゲルカラムクロマトグラフ
ィー（n-ヘキサン：酢酸エチル＝４：１）により精製し
て、３位水酸基の脱保護化合物 398.5 mg を得た（収率
９4.１％）。n-ヘキサン：酢酸エチルより再結晶して無
色針状晶を得た（ m.p. 155 ℃) 。1 H-NMR (400MHz/CDCl3) 0.69(s,3H,18-CH3), 0.90(d,6
H,J=6.5Hz,4'-CH3), 1.02(s,3H,19-CH3), 1.06(d,3H,J=
6.0Hz,21-CH3), 3.21(dt,1H,J=7.9Hz,1'-H), 3.23(m,1
H,20-H), 3.50-3.58(m,2H,3-H,1'-H), 5.35(dd,1H,J=5.
5Hz,6-H) 上記の脱保護体 371.2 mg をジクロルメタン２mlに溶解
してピリジン0.４mlを加えた後、無水酢酸0.５５mlを滴
下して室温で１日攪拌した。ジクロルメタン５０mlを加
え、２Ｎ塩酸（３０ml×２）、飽和重曹水（３０ml×
２）および水５０mlで洗浄し、脱水後に溶媒を留去し
た。シリカゲルカラムクロマトグラフィー（n-ヘキサ
ン：酢酸エチル＝１０：１）で精製し、３位アセトキシ
体 387.0 mg を得た（収率９4.１％）。メタノールより
再結晶して無色針状晶を得た（m.p. 75.5-76℃) 。1 H-NMR (400MHz/CDCl3) 0.69(s,3H,18-CH3), 0.90(d,6
H,J=6.5Hz,4'-CH3), 1.02(s,3H,19-CH3), 1.06(d,3H,J=
6.0Hz,21-CH3), 2.03(s,3H,AcO), 2.32(d,2H,J=7.0Hz,4
-H), 3.21(dt,1H,J=7.9Hz,1'-H), 3.24(m,1H,20-H), 3.
57(dt,1H,J=7.9Hz,1'-H), 4.60(m,1H,3-H), 5.37(dd,1
H,J=5.0Hz,6-H)3.35 g of the above silyl compound was added to 50 parts of ethanol.
It was dissolved in a mixture of 50 ml of tetrahydrofuran and 50 ml of tetrahydrofuran, 0.90 g of sodium borohydride was added under ice cooling, and the mixture was stirred at room temperature for 5 hours. 5% acetic acid was added to the solution, the solvent was distilled off, water was added, and the mixture was extracted with dichloromethane. Washing with water,
After dehydration, the solvent was distilled off, the residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 7: 1), and the carbonyl group at the 20-position was reduced to a hydroxyl group.
44 g was obtained (yield 72.4%). Recrystallization from methanol gave colorless needle crystals (mp 151 ° C). Sodium hydride (138.8 mg) was washed with n-hexane (1 ml x 3) and suspended in xylene (1 ml), and the above compound (606.7 mg) was dissolved in xylene (4 ml) and added to isopentyl chloride 0.87.
ml was added and the mixture was refluxed for 17 hours. After adding 10% citric acid and water and extracting with dichloromethane, washing with water and dehydration,
The solvent was distilled off. The residue was purified by silica gel column chromatography (n-hexane: dichloromethane = 3: 1) to obtain 490.8 mg of a compound having an isopentyloxy group introduced at the 20th position (yield 69.7%). Recrystallization from methanol gave colorless needle crystals (mp 82 ° C). 1 H-NMR (400MHz / CDCl 3 ) 0.05 (s, 6H, TBDMS Me), 0.69 (s,
3H, 18-CH 3 ), 0.88 (s, 9H, TBDMS t-Bu), 0.90 (d, 6H, J = 6.5
Hz, 4'-CH 3 ), 1.00 (s, 3H, 19-CH 3 ), 1.06 (d, 3H, J = 6.0Hz, 2
1-CH 3 ), 3.22 (dt, 1H, J = 7.9Hz, 1'-H), 3.25 (m, 1H, 20-H),
3.47 (m, 1H, 3-H), 3.57 (dt, 1H, J = 7.9Hz, 1'-H), 5.31 (d
d, 1H, J = 5.0Hz, 6-H) 547.0 mg of the above compound was dissolved in 23 mg of acetone, and a mixture of 0.05 ml of perchloric acid, 0.05 ml of water and 2 ml of acetone was added under ice cooling. After stirring at room temperature for 3 hours, 6 ml of saturated aqueous sodium hydrogen carbonate was added, acetone was distilled off, water was added, and the mixture was extracted with dichloromethane (30 ml × 3). After washing with water and dehydration, the solvent was distilled off, and the residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 4: 1) to obtain 398.5 mg of a deprotected compound at the 3-position hydroxyl group (yield 94. 1%). Recrystallization from n-hexane: ethyl acetate gave colorless needle crystals (mp 155 ° C). 1 H-NMR (400MHz / CDCl 3 ) 0.69 (s, 3H, 18-CH 3 ), 0.90 (d, 6
H, J = 6.5Hz, 4'-CH 3 ), 1.02 (s, 3H, 19-CH 3 ), 1.06 (d, 3H, J =
6.0Hz, 21-CH 3 ), 3.21 (dt, 1H, J = 7.9Hz, 1'-H), 3.23 (m, 1
H, 20-H), 3.50-3.58 (m, 2H, 3-H, 1'-H), 5.35 (dd, 1H, J = 5.
(5 Hz, 6-H) 371.2 mg of the above deprotected product was dissolved in 2 ml of dichloromethane, 0.4 ml of pyridine was added, 0.55 ml of acetic anhydride was added dropwise, and the mixture was stirred at room temperature for 1 day. Dichloromethane (50 ml) was added, 2N hydrochloric acid (30 ml x 2), saturated sodium bicarbonate water (30 ml x
It was washed with 2) and 50 ml of water, and the solvent was distilled off after dehydration. Purification by silica gel column chromatography (n-hexane: ethyl acetate = 10: 1) yielded 387.0 mg of 3-position acetoxy compound (yield 94.1%). Recrystallization from methanol gave colorless needle crystals (mp 75.5-76 ° C). 1 H-NMR (400MHz / CDCl 3 ) 0.69 (s, 3H, 18-CH 3 ), 0.90 (d, 6
H, J = 6.5Hz, 4'-CH 3 ), 1.02 (s, 3H, 19-CH 3 ), 1.06 (d, 3H, J =
6.0Hz, 21-CH 3 ), 2.03 (s, 3H, AcO), 2.32 (d, 2H, J = 7.0Hz, 4
-H), 3.21 (dt, 1H, J = 7.9Hz, 1'-H), 3.24 (m, 1H, 20-H), 3.
57 (dt, 1H, J = 7.9Hz, 1'-H), 4.60 (m, 1H, 3-H), 5.37 (dd, 1
(H, J = 5.0Hz, 6-H)

【００１９】上記アセトキシ体３６8.７mgをジクロルメ
タン２mlに溶解し、メタクロル過安息香酸２１6.７mgを
ジクロルメタン４mlに溶解して氷冷下に加え、室温で８
０分間攪拌した。ジクロルメタン４０mlを加えて、１０
％ NaHSO3 (30 ml×２）、飽和重曹水(30 ml×２）、水
５０mlで洗浄し、脱水した後に溶媒を留去した。シリカ
ゲルカラムクロマトグラフィー（n-ヘキサン：酢酸エチ
ル＝１０：１）により精製して、エポキシ体 283.5 mg
を無色油状物として得た（収率７4.１％）。 主生成物：1H-NMR (400MHz/CDCl3) 0.62(s,3H,18-CH3),
0.88(d,6H,J=7.0Hz,4'-CH3), 1.04(d,3H,J=6.0Hz,21-C
H3), 1.08(s,3H,19-CH3), 2.01(s,3H,AcO), 2.88(d,1H,
J=4.5Hz,6-H), 3.15-3.25(m,2H,1'-H, 20-H), 3.55(m,1
H,1'-H), 4.95(m,1H,3-H), 副生成物：1H-NMR (400MHz/CDCl3) 0.65(s,3H,18-CH3),
0.88(d,6H,J=7.0Hz,4'-CH3), 1.01(s,3H,19-CH3), 1.0
4(d,3H,J=6.0Hz,21-CH3), 2.03(s,3H,AcO), 3.07(d,1H,
J=4.0Hz,6-H), 3.15-3.25(m,2H,1'-H, 20-H), 3.55(m,1
H,1'-H), 4.76(m,1H,3-H), 上記のエポキシ体２７3.８mgをアセトン８mlに溶解し、
過塩素酸0.０５ml、水0.０５ml、およびアセトン２mlの
混合物を氷冷下に加えて、室温で７時間攪拌した。飽和
重曹水２mlを加えてアセトンを留去し、水を加えて酢酸
エチルで抽出(30 ml×２）した。飽和食塩水で洗浄し、
脱水して溶媒を留去し、残渣をシリカゲルカラムクロマ
トグラフィー（n-ヘキサン：酢酸エチル＝２：１）によ
り精製してエポキシが開環したジオール体 262.8 mg を
無色固体として得た（収率９2.５％）。1 H-NMR (400MHz/CDCl3) 0.69(s,3H,18-CH3), 0.89(d,6
H,J=7.0Hz,4'-CH3), 1.05(d,3H,J=6.0Hz,21-CH3), 1.19
(s,3H,19-CH3), 2.02(s,3H,AcO), 3.19(dt,1H,J=7.9Hz,
1'-H), 3.24(m,1H,20-H), 3.53-3.56(m,2H,1'-H,6H),
5.15(m,1H,3-H) ピリジニウムクロロクロメート0.３４ｇ、Al2O3 1.１４
ｇにジクロルメタン３mlを加えてアルゴン置換し、激し
く攪拌しつつ上記のジオール体２４2.８mgをジクロルメ
タン３mlに溶解して氷冷下に加えた。室温で2.５時間攪
拌し、後処理することなくシリカゲルカラムクロマトグ
ラフィー（n-ヘキサン：酢酸エチル＝５：１）で精製し
て、６位ケトン体 225.3 mg を得た（収率９3.１％）。
n-ヘキサンより再結晶して無色針状晶を得た（m.p. 177
℃) 。1 H-NMR (400MHz/CDCl3) 0.65(s,3H,18-CH3), 0.83(s,3
H,19-CH3), 0.89(d,6H,J=6.5Hz,4'-CH3), 1.06(d,3H,J=
6.0Hz,21-CH3), 2.02(s,3H,AcO), 2.12(dd,1H,J=5.14H
z,7-beta-H), 2.75(t,1H,J=13Hz,7-alph-H), 3.16-3.27
(m,1H,1'-H,20-H),3.58(dt,1H,J=7.9Hz,1'-H), 5.03(m,
1H,3-H) 上記の６位ケトン体 200.5 mg をメタノールに溶解し、
氷冷下で２Ｎ水酸化カリウム1.０８mlをゆっくり滴下し
た。室温で１日攪拌した後、５％酢酸５mlにより中和し
てメタノールを留去した。水を加えて酢酸エチル抽出し
（３０ml×３）、食塩水で洗浄した後、脱水して溶媒を
留去した。シリカゲルカラムクロマトグラフィー（n-ヘ
キサン：酢酸エチル＝１：１）により精製して、１７1.
０mgの目的物を得た（収率９3.９％）。 YS-330： m.p. 232 ℃（n-ヘキサン／酢酸エチル） Anal. (C26H44O4: X=0, R=-CH(CH3)-O-CH2CH2CH(CH3)2)1 H-NMR (400MHz/CDCl3) 0.66(s,3H,18-CH3), 0.82(s,3
H,19-CH3), 0.88(t,6H,24-CH3), 1.06(d,3H,21-CH3),
2.11-2.16(m), 2.72(t,1H,J=13Hz), 3.16-3.25(m,2H),
3.57(dt,1H), 3.97(m,1H)368.7 mg of the acetoxy compound was dissolved in 2 ml of dichloromethane, 216.7 mg of metachloroperbenzoic acid was dissolved in 4 ml of dichloromethane, and the mixture was added under ice-cooling.
Stir for 0 minutes. Add 40 ml of dichloromethane and add 10
% NaHSO 3 (30 ml × 2), saturated aqueous sodium hydrogen carbonate (30 ml × 2), and water (50 ml), and the solvent was distilled off after dehydration. Purified by silica gel column chromatography (n-hexane: ethyl acetate = 10: 1), epoxy compound 283.5 mg
Was obtained as a colorless oil (yield 74.1%). Main product: 1 H-NMR (400MHz / CDCl 3 ) 0.62 (s, 3H, 18-CH 3 ),
0.88 (d, 6H, J = 7.0Hz, 4'-CH 3 ), 1.04 (d, 3H, J = 6.0Hz, 21-C
H 3 ), 1.08 (s, 3H, 19-CH 3 ), 2.01 (s, 3H, AcO), 2.88 (d, 1H,
J = 4.5Hz, 6-H), 3.15-3.25 (m, 2H, 1'-H, 20-H), 3.55 (m, 1
H, 1'-H), 4.95 (m, 1H, 3-H), by-product: 1 H-NMR (400MHz / CDCl 3 ) 0.65 (s, 3H, 18-CH 3 ),
0.88 (d, 6H, J = 7.0Hz, 4'-CH 3 ), 1.01 (s, 3H, 19-CH 3 ), 1.0
4 (d, 3H, J = 6.0Hz, 21-CH 3 ), 2.03 (s, 3H, AcO), 3.07 (d, 1H,
J = 4.0Hz, 6-H), 3.15-3.25 (m, 2H, 1'-H, 20-H), 3.55 (m, 1
H, 1'-H), 4.76 (m, 1H, 3-H), 273.8 mg of the above epoxy compound is dissolved in 8 ml of acetone,
A mixture of 0.05 ml of perchloric acid, 0.05 ml of water, and 2 ml of acetone was added under ice cooling, and the mixture was stirred at room temperature for 7 hours. 2 ml of saturated aqueous sodium hydrogen carbonate was added, acetone was distilled off, water was added, and the mixture was extracted with ethyl acetate (30 ml × 2). Washed with saturated saline,
After dehydration, the solvent was distilled off, and the residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 2: 1) to obtain 262.8 mg of the epoxy-opened diol derivative as a colorless solid (yield 92 .5%). 1 H-NMR (400MHz / CDCl 3 ) 0.69 (s, 3H, 18-CH 3 ), 0.89 (d, 6
H, J = 7.0Hz, 4'-CH 3 ), 1.05 (d, 3H, J = 6.0Hz, 21-CH 3 ), 1.19
(s, 3H, 19-CH 3 ), 2.02 (s, 3H, AcO), 3.19 (dt, 1H, J = 7.9Hz,
1'-H), 3.24 (m, 1H, 20-H), 3.53-3.56 (m, 2H, 1'-H, 6H),
5.15 (m, 1H, 3-H) Pyridinium chlorochromate 0.34g, Al 2 O 3 1.14
Dichloromethane (3 ml) was added to g and the atmosphere was replaced with argon. 242.8 mg of the above-mentioned diol compound was dissolved in dichloromethane (3 ml) with vigorous stirring, and the mixture was added under ice cooling. The mixture was stirred at room temperature for 2.5 hours, and purified by silica gel column chromatography (n-hexane: ethyl acetate = 5: 1) without post-treatment to obtain 225.3 mg of 6-position ketone body (yield 93.1). %).
Recrystallization from n-hexane gave colorless needle crystals (mp 177
° C). 1 H-NMR (400MHz / CDCl 3 ) 0.65 (s, 3H, 18-CH 3 ), 0.83 (s, 3
H, 19-CH 3 ), 0.89 (d, 6H, J = 6.5Hz, 4'-CH 3 ), 1.06 (d, 3H, J =
6.0Hz, 21-CH 3 ), 2.02 (s, 3H, AcO), 2.12 (dd, 1H, J = 5.14H
z, 7-beta-H), 2.75 (t, 1H, J = 13Hz, 7-alph-H), 3.16-3.27
(m, 1H, 1'-H, 20-H), 3.58 (dt, 1H, J = 7.9Hz, 1'-H), 5.03 (m,
1H, 3-H) 200.5 mg of the above 6-position ketone body was dissolved in methanol,
Under ice-cooling, 1.08 ml of 2N potassium hydroxide was slowly added dropwise. After stirring at room temperature for 1 day, the mixture was neutralized with 5 ml of 5% acetic acid and methanol was distilled off. Water was added and the mixture was extracted with ethyl acetate (30 ml x 3), washed with brine, dehydrated and the solvent was distilled off. Purification by silica gel column chromatography (n-hexane: ethyl acetate = 1: 1) gave 171.
0 mg of the desired product was obtained (yield 93.9%). YS-330: mp 232 ℃ (n-hexane / ethyl acetate) Anal. (C 26 H 44 O 4 : X = 0, R = -CH (CH 3 ) -O-CH 2 CH 2 CH (CH 3 ) 2 ) 1 H-NMR (400MHz / CDCl 3 ) 0.66 (s, 3H, 18-CH 3 ), 0.82 (s, 3
H, 19-CH 3 ), 0.88 (t, 6H, 24-CH 3 ), 1.06 (d, 3H, 21-CH 3 ),
2.11-2.16 (m), 2.72 (t, 1H, J = 13Hz), 3.16-3.25 (m, 2H),
3.57 (dt, 1H), 3.97 (m, 1H)

【００２０】例５ （ＹＳ−５１０）３−ハイドロキシ−デヒドロエピアン
ドロテロン3.１２ｇをジクロルメタン５０mlに溶解し、
ジイソプロピルエチルアミン7.２８ｇ、続いて２−クロ
ロメトキシエチルトリメチルシラン5.５４ｇを室温で加
えた。この混合物を室温で９０分放置した後に飽和重曹
水を加えて反応を停止し、水１５０mlおよびジクロルメ
タン１００mlを加えてジクロルメタン層を分離した。水
層をジクロルメタン（２００ml×２）で抽出し、有機層
をあわせて乾燥して濃縮した。残渣をシリカゲルカラム
クロマトグラフィー（n-ヘキサン：酢酸エチル＝２：0.
３）により精製して３位水酸基の保護体5.２４ｇを得
た。エタノール／水から再結晶して白色結晶を得た（m.
p. 77.5-79℃) 。1 H-NMR (400MHz/CDCl3) 0.01(s,9H), 0.93(t,2H,J=7.0H
z), 0.88(s,3H), 1.02(s,3H), 2.08(dd,1H,J=19Hz,8.0H
z), 1.06-2.48(m,23H), 2.45(dd,1H,J=19Hz,8.0Hz), 3.
43(m,1H), 3.62(t,2H,J=8.0Hz), 4.72(s,2H), 5.37(d,1
H,J=5.0Hz) 上記の３位水酸基保護体5.２０ｇのジクロルメタン溶液
２５mlに、ジクロルメタン４０mlに溶解した７０％メタ
クロル過安息香酸3.２２ｇを加えて室温で３０分間放置
した。この混合物を１０％ NaHSO3 （１００ml×２）、
続いてNaHCO3（１５０ml×２）で洗浄し、有機層を乾燥
して濃縮した。残渣をシリカゲルカラムクロマトグラフ
ィー（n-ヘキサン：酢酸エチル＝４：１）により精製し
てエポキシ体4.３７ｇを白色結晶として得た。1 H-NMR (400MHz/CDCl3) 0.01(s,9H), 0.81(s,3H), 2.93
(d,1H,J=4.5Hz), 3.11(d,1H,β−エポキシ体), 3.59(m,
1H), 3.78(m,1H，α−エポキシ体) 上記エポキシ体4.３７ｇをアセトン１５０mlおよび水１
２mlの混合物に溶解して過塩素酸（７０％）1.４mlを滴
下した。この溶液を室温で３時間放置した後、飽和重曹
水を加えて反応を停止した。この混合物を濃縮して残渣
をジクロルメタンおよび水に分配し、有機層を乾燥して
濃縮した。残渣をシリカゲルカラムクロマトグラフィー
（n-ヘキサン：酢酸エチル＝１：１）で精製してエポキ
シが開裂したジオール体3.４３ｇを得た（収率７８
％）。n-ヘキサン／酢酸エチルから再結晶して白色結晶
を得た（m.p. 155-157℃) 。Example 5 (YS-510) 3.12 g of 3-hydroxy-dehydroepiandroteron were dissolved in 50 ml of dichloromethane,
7.28 g of diisopropylethylamine was added, followed by 5.54 g of 2-chloromethoxyethyltrimethylsilane at room temperature. The mixture was allowed to stand at room temperature for 90 minutes, saturated aqueous sodium hydrogen carbonate was added to stop the reaction, and 150 ml of water and 100 ml of dichloromethane were added to separate the dichloromethane layer. The aqueous layer was extracted with dichloromethane (200 ml × 2), the organic layers were combined, dried and concentrated. The residue was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 2: 0.
Purification by 3) yielded 5.24 g of a protected 3-hydroxyl group. Recrystallization from ethanol / water gave white crystals (m.
p. 77.5-79 ° C). 1 H-NMR (400MHz / CDCl 3 ) 0.01 (s, 9H), 0.93 (t, 2H, J = 7.0H
z), 0.88 (s, 3H), 1.02 (s, 3H), 2.08 (dd, 1H, J = 19Hz, 8.0H
z), 1.06-2.48 (m, 23H), 2.45 (dd, 1H, J = 19Hz, 8.0Hz), 3.
43 (m, 1H), 3.62 (t, 2H, J = 8.0Hz), 4.72 (s, 2H), 5.37 (d, 1
(H, J = 5.0 Hz) 3.22 g of 70% metachloroperbenzoic acid dissolved in 40 ml of dichloromethane was added to 25 ml of a solution of 5.20 g of the above-mentioned 3-hydroxyl group protector in 25 ml of dichloromethane, and the mixture was allowed to stand at room temperature for 30 minutes. This mixture was added with 10% NaHSO 3 (100 ml × 2),
Then, it was washed with NaHCO 3 (150 ml × 2), and the organic layer was dried and concentrated. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 4: 1) to obtain 4.37 g of an epoxy compound as white crystals. 1 H-NMR (400MHz / CDCl 3 ) 0.01 (s, 9H), 0.81 (s, 3H), 2.93
(d, 1H, J = 4.5Hz), 3.11 (d, 1H, β-epoxy body), 3.59 (m,
1H), 3.78 (m, 1H, α-epoxy body) 4.37 g of the above epoxy body was added to 150 ml of acetone and 1
It was dissolved in 2 ml of the mixture and 1.4 ml of perchloric acid (70%) was added dropwise. After leaving this solution at room temperature for 3 hours, saturated aqueous sodium hydrogen carbonate was added to stop the reaction. The mixture was concentrated, the residue was partitioned between dichloromethane and water, the organic layer was dried and concentrated. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 1: 1) to obtain 3.43 g of epoxy-cleaved diol (yield 78).
%). Recrystallization from n-hexane / ethyl acetate gave white crystals (mp 155-157 ° C).

【００２１】上記のジオール体3.３７ｇをエタノール１
２０mlに溶解し、ナトリウムボロハイドライド４３９mg
を０℃で加えた。室温で１時間攪拌した後、この混合物
を濃縮し残渣をジクロルメタンおよび水に分配した。水
層をジクロルメタン（２×２００ml）で抽出し、有機層
を合わせて乾燥して濃縮した。残渣をシリカゲルカラム
クロマトグラフィー（n-ヘキサン：酢酸エチル＝２：
３）により精製して１７位ハイドロキシ体3.３６ｇを得
た。n-ヘキサン／酢酸エチルから再結晶すして白色結晶
を得た（m.p. 122-123℃) 。1 H-NMR (400MHz/CDCl3) 0.025(s,9H), 0.75(s,3H), 0.9
3(t,2H,J=8,5Hz), 1.18(s,3H), 1.05-2.14(m,22H), 3.5
2(brs,1H), 3.63(m,3H), 3.98(m,1H), 4.72(s,2H)3.37 g of the above-mentioned diol body was added to ethanol 1
Dissolved in 20 ml, sodium borohydride 439 mg
Was added at 0 ° C. After stirring at room temperature for 1 hour, the mixture was concentrated and the residue was partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane (2 x 200 ml), the organic layers were combined, dried and concentrated. The residue was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 2:
Purification according to 3) yielded 3.36 g of the 17-position hydroxy compound. Recrystallization from n-hexane / ethyl acetate gave white crystals (mp 122-123 ° C). 1 H-NMR (400MHz / CDCl 3 ) 0.025 (s, 9H), 0.75 (s, 3H), 0.9
3 (t, 2H, J = 8,5Hz), 1.18 (s, 3H), 1.05-2.14 (m, 22H), 3.5
2 (brs, 1H), 3.63 (m, 3H), 3.98 (m, 1H), 4.72 (s, 2H)

【００２２】ジクロルメタン0.３mlにピリジン0.０５を
溶解し、５０mgの上記１７位ハイドロキシ体を加え、続
いてブチリルクロライド0.０２１ｇ（1.５当量）のジク
ロルメタン溶液（0.３ml）を加えた。さらに１５分毎に
原料が消失するまで0.５当量ずつのブチリルクロライド
を加えた。ジクロルメタン２０ml加えて水洗し（２０ml
×２）、乾燥して濃縮した。残渣をシリカゲルカラムク
ロマトグラフィー（n-ヘキサン：酢酸エチル＝２：１）
により精製して１７位ブチリルオキシ体５0.３ｇを無色
油状物として得た（収率７8.６％）。1 H-NMR (400MHz/CDCl3) 0.02(s,9H), 0.80(s,3H), 0.91
-2.29(m,33H), 3.53(brs,1H), 3.62(t,2H,J=8.0Hz), 3.
98(m,1H), 4.61(t,2H,J=8Hz), 4.72(s,2H) ピリジニウムクロロクロメート（ＰＣＣ）0.３５ｇおよ
びAl2O3 1.１３ｇをジクロルメタン８mlに懸濁し、アル
ゴン雰囲気中で激しく攪拌しつつ、上記の１７位ブチリ
ルオキシ体をジクロルメタン８mlに溶解して氷冷下に加
えた。室温で２時間攪拌し、後処理することなくシリカ
ゲルカラムクロマトグラフィー（n-ヘキサン：酢酸エチ
ル＝４：１）で精製して、６位ケトン体 223 mg を白色
結晶として得た（収率７９％）。1 H-NMR (400MHz/CDCl3) 0.02(s,9H), 0.81(s,3H), 0.92
-2.14(m,26H), 2.26(t,2H,J=7Hz), 2.74(t,2H,J=13Hz),
3.53(brs,1H), 3.62(t,2H,J=9.0Hz), 3.87(m,1H), 4.6
6(t,2H,J=8Hz), 4.72(s,2H) 上記の化合物５8.５mgをジクロルメタン１mlに溶解し、
トリフルオロ酢酸２mlを０℃で加えた。混合物を０℃で
３０分間放置した後、水３０mlを加えて反応を停止し、
ジクロルメタン（３０ml×２）で抽出した。飽和重曹水
（３０ml×２）で洗浄し、乾燥して濃縮した。残渣をシ
リカゲルカラムクロマトグラフィー（n-ヘキサン：酢酸
エチル＝１：４）により精製して目的物３7.７mgを白色
結晶として得た。 YS-510： m.p. 227-228 ℃（n-ヘキサン／酢酸エチル） Anal. (C23H36O5: X=O, R=-O-CO-CH2CH2CH3)1 H-NMR (400MHz/CDCl3) 0.77(s,3H), 0.81(s,3H), 0.94
(t,3H,7-H), 1.18-2.29(m,15H), 1.69-1.60 (hex,2H,J=
7.0Hz), 2.12(dd,1H,J=12.5Hz,4.5Hz), 2.22(s,1H), 2,
27(t,1H,J=7.0Hz), 2.74(t,1H,J=12.5Hz), 3.96(m,1H),
4.64(2H,J=8.0Hz)Pyridine (0.05) was dissolved in 0.3 ml of dichloromethane, and 50 mg of the above 17-position hydroxy compound was added, followed by addition of 0.021 g (1.5 equivalents) of butyryl chloride in dichloromethane solution (0.3 ml). It was Further, every 15 minutes, 0.5 equivalent of butyryl chloride was added until the raw material disappeared. Add 20 ml of dichloromethane and wash with water (20 ml
X2), dried and concentrated. Silica gel column chromatography of the residue (n-hexane: ethyl acetate = 2: 1)
Purification was carried out to obtain 50.3 g of butyryloxy derivative at the 17-position as a colorless oil (yield 78.6%). 1 H-NMR (400MHz / CDCl 3 ) 0.02 (s, 9H), 0.80 (s, 3H), 0.91
-2.29 (m, 33H), 3.53 (brs, 1H), 3.62 (t, 2H, J = 8.0Hz), 3.
98 (m, 1H), 4.61 (t, 2H, J = 8Hz), 4.72 (s, 2H) 0.35 g of pyridinium chlorochromate (PCC) and 1.13 g of Al 2 O 3 are suspended in 8 ml of dichloromethane, and the atmosphere is argon. While vigorously stirring in the above, the above 17-butyryloxy derivative was dissolved in 8 ml of dichloromethane and added under ice cooling. The mixture was stirred at room temperature for 2 hours and purified by silica gel column chromatography (n-hexane: ethyl acetate = 4: 1) without post-treatment to obtain 223 mg of 6-position ketone body as white crystals (yield 79%. ). 1 H-NMR (400MHz / CDCl 3 ) 0.02 (s, 9H), 0.81 (s, 3H), 0.92
-2.14 (m, 26H), 2.26 (t, 2H, J = 7Hz), 2.74 (t, 2H, J = 13Hz),
3.53 (brs, 1H), 3.62 (t, 2H, J = 9.0Hz), 3.87 (m, 1H), 4.6
6 (t, 2H, J = 8Hz), 4.72 (s, 2H) Dissolve 58.5 mg of the above compound in 1 ml of dichloromethane,
2 ml of trifluoroacetic acid was added at 0 ° C. After leaving the mixture at 0 ° C for 30 minutes, 30 ml of water was added to stop the reaction,
It was extracted with dichloromethane (30 ml x 2). The extract was washed with saturated aqueous sodium hydrogen carbonate (30 ml x 2), dried and concentrated. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 1: 4) to obtain 37.7 mg of the desired product as white crystals. YS-510: mp 227-228 ℃ (n-hexane / ethyl acetate) Anal. (C 23 H 36 O 5 : X = O, R = -O-CO-CH 2 CH 2 CH 3 ) 1 H-NMR ( 400MHz / CDCl 3 ) 0.77 (s, 3H), 0.81 (s, 3H), 0.94
(t, 3H, 7-H), 1.18-2.29 (m, 15H), 1.69-1.60 (hex, 2H, J =
7.0Hz), 2.12 (dd, 1H, J = 12.5Hz, 4.5Hz), 2.22 (s, 1H), 2,
27 (t, 1H, J = 7.0Hz), 2.74 (t, 1H, J = 12.5Hz), 3.96 (m, 1H),
4.64 (2H, J = 8.0Hz)

【００２３】例４および例５と同様にして以下の化合物
を製造した。 YS-500： m.p. 255-256 ℃（n-ヘキサン／酢酸エチル） Anal. (C21H32O5: X=O, R=-O-CO-CH3) YS-520： m.p. 205-206 ℃（n-ヘキサン／酢酸エチル） Anal. (C25H40O5: X=O, R=-O-CO-(CH2)4CH3) YS-530： m.p. 186-187 ℃（n-ヘキサン／酢酸エチル） Anal. (C27H44O5: X=O, R=-O-CO-(CH2)6CH3) YS-540： m.p. 182.5-183.5 ℃（n-ヘキサン／酢酸エチ
ル） Anal. (C29H48O5: X=O, R=-O-CO-(CH2)8CH3) YS-550： m.p. 179-180 ℃（n-ヘキサン／酢酸エチル） Anal. (C31H52O5: X=O, R=-O-CO-(CH2)10CH3) YS-560： m.p. 174-175 ℃（n-ヘキサン／酢酸エチル） Anal. (C33H56O5: X=O, R=-O-CO-(CH2)12CH3) YS-570： m.p. 273.5-274.5 ℃（n-ヘキサン／酢酸エチ
ル） Anal. (C26H34O5: X=O, R=-O-CO-C6H5) YS-310： m.p. 258 ℃（n-ヘキサン／酢酸エチル） Anal. (C21H36O4: X=O, R=-CH(CH3)-O-CH3) YS-330： m.p. 232 ℃（n-ヘキサン／酢酸エチル） Anal. (C26H44O4: X=O, R=-CH(CH3)──O-C5H11) YS-340： m.p. 238 ℃（n-ヘキサン／酢酸エチル） Anal. (C26H44O4: X=O, R=-CH(CH3) ---O-C5H11) YS-350： m.p. 146 ℃（n-ヘキサン／酢酸エチル） Anal. (C28H48O4: X=O, R=-CH(CH3)-O-C7H15)The following compounds were prepared in the same manner as in Examples 4 and 5. YS-500: mp 255-256 ℃ (n-hexane / ethyl acetate) Anal. (C 21 H 32 O 5 : X = O, R = -O-CO-CH 3 ) YS-520: mp 205-206 ℃ (N-hexane / ethyl acetate) Anal. (C 25 H 40 O 5 : X = O, R = -O-CO- (CH 2 ) 4 CH 3 ) YS-530: mp 186-187 ℃ (n-hexane / Ethyl acetate) Anal. (C 27 H 44 O 5 : X = O, R = -O-CO- (CH 2 ) 6 CH 3 ) YS-540: mp 182.5-183.5 ℃ (n-hexane / ethyl acetate) Anal. (C 29 H 48 O 5 : X = O, R = -O-CO- (CH 2 ) 8 CH 3 ) YS-550: mp 179-180 ℃ (n-hexane / ethyl acetate) Anal. 31 H 52 O 5 : X = O, R = -O-CO- (CH 2 ) 10 CH 3 ) YS-560: mp 174-175 ℃ (n-hexane / ethyl acetate) Anal. (C 33 H 56 O 5 : X = O, R = -O-CO- (CH 2 ) 12 CH 3 ) YS-570: mp 273.5-274.5 ℃ (n-hexane / ethyl acetate) Anal. (C 26 H 34 O 5 : X = O, R = -O-CO-C 6 H 5 ) YS-310: mp 258 ℃ (n-hexane / ethyl acetate) Anal. (C 21 H 36 O 4 : X = O, R = -CH (CH 3 ) -O-CH 3 ) YS-330: mp 232 ℃ (n-hexane / ethyl acetate) Anal. (C 26 H 44 O 4 : X = O, R = -CH (CH 3 ) ── OC 5 H 11 ) YS-340: mp 238 ℃ (n-hexane / ethyl acetate) Anal. (C 26 H 44 O 4 : X = O, R = -CH (CH 3 ) --- OC 5 H 11 ) YS-350: mp 146 ℃ (n-hexane / ethyl acetate) Anal. (C 28 H 48 O 4 : X = O, R = -CH (CH 3 ) -OC 7 H 15 )

【００２４】試験例 CN-TPBP(Cytosolic-Nuclear Tumor Promoter-Specific
Binding Protein)を含むフラクション、およびPKC(Prot
ein Kinase C) を含むフラクションを、以下のようにし
て調製した。凍結保存（−８０℃）された懸濁培養ヒー
ラ細胞を0.６MKCl-20 mM Tris-HCl (pH 8.0) 中でホモ
ジナイズした後に超遠心し、得られた上清をQAE-セファ
ロースカラムクロマトグラフィーに付した。各フラクシ
ョンを、ラベル化 12-O−テトラデカノイルホルボール
13-アセテート（[3H]TPA, NEN)を用いたTPA-特異的結
合活性、PKC アッセイキット(Amersham)を用いたPKC 活
性、ならびにPKCsに対する抗血清及び／又は抗体(Amers
ham)を用いたウエスタンブロットによりモニターして、
目的のフラクションを得た。上記の化合物について、CN
-TPBP に対する結合親和性を、[3H]TPA をプローブとし
て用いたデキストラン被覆活性炭(dextran-coated char
coal) 法によりリガンド競合アッセイを行った。結果を
表２に示す。Test Example CN-TPBP (Cytosolic-Nuclear Tumor Promoter-Specific
Fraction containing Binding Protein) and PKC (Prot
The fraction containing ein Kinase C) was prepared as follows. HeLa cells in suspension culture that had been cryopreserved (-80 ° C) were homogenized in 0.6 M KCl-20 mM Tris-HCl (pH 8.0) and then ultracentrifuged, and the resulting supernatant was subjected to QAE-Sepharose column chromatography. Attached. Label each fraction with labeled 12-O-tetradecanoylphorbol.
TPA-specific binding activity using 13-acetate ([ 3 H] TPA, NEN), PKC activity using PKC assay kit (Amersham), and antiserum and / or antibody against PKCs (Amers)
ham) by Western blotting,
The desired fraction was obtained. For the above compounds, CN
-The binding affinity for TPBP was measured by using dextran-coated charcoal ([ 3 H] TPA) as a probe.
The ligand competition assay was performed by the coal method. The results are shown in Table 2.

【００２５】[0025]

【表２】 CN-TPBP および PKCに対する[3H]TPA 結合の％阻害 ──────────────────────────────────── 化合物 X R CN-TPBP PKC 100 倍* 1,000 倍* 1,000 倍* ──────────────────────────────────── YS-64 =O -CH(CH3)-(CH2)5CH(CH3)2 100 0 YS-149 =O -CH(CH3)2 11 48 0 YS-151 =O -CH(CH3)-CH2CH3 1 57 - YS-152 =O -CH(CH3)-(CH2)2CH3 26 46 - YS-153 =O -CH(CH3)-(CH2)3CH3 41 88 - YS-154 =O -CH(CH3)-(CH2)4CH3 54 86 2 YS-155 =O -CH(CH3)-(CH2)5CH3 51 98 2 YS-156 =O -CH(CH3)-(CH2)6CH3 35 88 4 YS-157 =O -CH(CH3)-(CH2)7CH3 26 82 - YS-161 =O -CH(CH3)-(CH2)2C6H5 27 41 - YS-126 =O -CH(CH3)-CH=CHCH2CH(CH3)2 ** 14 10 - YS-510 =O -O-CO-CH2CH2CH3 0 2 - YS-520 =O -O-CO-(CH2)4CH3 0 2 - YS-530 =O -O-CO-(CH2)6CH3 3 43 - YS-540 =O -O-CO-(CH2)8CH3 22 64 - YS-550 =O -O-CO-(CH2)10CH3 11 56 - YS-560 =O -O-CO-(CH2)12CH3 6 44 - YS-570 =O -O-CO-C6H5 2 17 - ──────────────────────────────────── * 過剰** トランス体[Table 2] [for CN-TPBP and PKC]3%] Inhibition of H] TPA binding Double*1,000 times* 1,000 times* ──────────────────────────────────── YS-64 = O -CH (CH3)-(CH2)FiveCH (CH3)2 100 0 YS-149 = O -CH (CH3)2 11 48 0 YS-151 = O -CH (CH3) -CH2CH3 1 57-YS-152 = O -CH (CH3)-(CH2)2CH3 26 46-YS-153 = O -CH (CH3)-(CH2)3CH3 41 88-YS-154 = O -CH (CH3)-(CH2)FourCH3 54 86 2 YS-155 = O -CH (CH3)-(CH2)FiveCH3 51 98 2 YS-156 = O -CH (CH3)-(CH2)6CH3 35 88 4 YS-157 = O -CH (CH3)-(CH2)7CH3 26 82-YS-161 = O -CH (CH3)-(CH2)2C6HFive 27 41-YS-126 = O -CH (CH3) -CH = CHCH2CH (CH3)2 ** 14 10-YS-510 = O -O-CO-CH2CH2CH3 0 2-YS-520 = O -O-CO- (CH2)FourCH3 0 2-YS-530 = O -O-CO- (CH2)6CH3 3 43-YS-540 = O -O-CO- (CH2)8CH3 22 64-YS-550 = O -O-CO- (CH2)TenCH3 11 56-YS-560 = O -O-CO- (CH2)12CH3 6 44-YS-570 = O -O-CO-C6HFive 2 17-──────────────────────────────────── * excess** Trans body

【００２６】[0026]

【発明の効果】発がんプロモーター結合蛋白CN-TPBP(Cy
tosolic-Nuclear Tumor Promoter-Specific Binding Pr
otein)に対して強い親和性を示し、TPA 等の発がんプロ
モータのCN-TPBP に対する結合を拮抗的に阻害する。加
えて、本発明の阻害剤は、ホルボールエステルやテレオ
シジンのような蛋白質リン酸化酵素活性化作用を有しな
いので、発がんプロモーターの作用を抑制することがで
き、発がんプロモーターの作用抑制剤あるいは発がん抑
制剤として有用である。EFFECT OF THE INVENTION Carcinogenic promoter binding protein CN-TPBP (Cy
tosolic-Nuclear Tumor Promoter-Specific Binding Pr
It has a strong affinity for otein) and competitively inhibits the binding of carcinogenic promoters such as TPA to CN-TPBP. In addition, since the inhibitor of the present invention does not have a protein phosphatase activating effect such as phorbol ester and tereosidine, it can suppress the action of a carcinogenic promoter, and thus the action inhibitor of the carcinogenic promoter or the carcinogenic suppressant. It is useful as an agent.

Claims (4)

【特許請求の範囲】[Claims] 【請求項１】 以下の式： 【化１】 〔式中、X は＝O または -OHを示し、R は-O-CO-R1また
は-CHR2-R3を示す（R1は直鎖または分枝したアルキル
基、直鎖または分枝したアルケニル基、直鎖または分枝
したアラルキル基、あるいは置換または非置換フェニル
基であり、R2は水素原子、あるいは直鎖または分枝した
低級アルキル基であり、R3は直鎖または分枝したアルキ
ル基、直鎖または分枝したアルケニル基、直鎖または分
枝したアルコキシ基、直鎖または分枝したアルケニルオ
キシ基、直鎖または分枝したアラルキル基、あるいは置
換または非置換フェニル基である）〕で示される化合物
を有効成分として含む発がんプロモーター阻害剤。1. The following formula: [In the formula, X represents = O or -OH, and R represents -O-CO-R 1 or -CHR 2 -R 3 (R 1 represents a linear or branched alkyl group, a linear or branched alkyl group. An alkenyl group, a linear or branched aralkyl group, or a substituted or unsubstituted phenyl group, R 2 is a hydrogen atom, or a linear or branched lower alkyl group, and R 3 is a linear or branched An alkyl group, a linear or branched alkenyl group, a linear or branched alkoxy group, a linear or branched alkenyloxy group, a linear or branched aralkyl group, or a substituted or unsubstituted phenyl group. )] A carcinogenic promoter inhibitor comprising the compound represented by the formula (1) as an active ingredient. 【請求項２】 発がんプロモーターがホルボールエステ
ル類およびテレオシジン類から選ばれる請求項１記載の
阻害剤。2. The inhibitor according to claim 1, wherein the carcinogenic promoter is selected from phorbol esters and teleocidins. 【請求項３】 発がん抑制剤として用いる請求項１記載
の阻害剤。3. The inhibitor according to claim 1, which is used as a carcinogenesis inhibitor. 【請求項４】 以下の式： 【化２】 （式中、X は＝O を示し、R は-O-CO-R1または-CHR2-R3
を示す（R1は直鎖または分枝したアルキル基、直鎖また
は分枝したアルケニル基、直鎖または分枝したアラルキ
ル基、あるいは置換または非置換フェニル基であり、R2
は水素原子、あるいは直鎖または分枝した低級アルキル
基であり、R3は直鎖または分枝したアルキル基、直鎖ま
たは分枝したアルケニル基、直鎖または分枝したアルコ
キシ基、直鎖または分枝したアルケニルオキシ基、直鎖
または分枝したアラルキル基、あるいは置換または非置
換フェニル基である) 。ただし、R は-CH(CH3)(CH2)3CH
(CH3)2であることはない。）で示される化合物。4. The following formula: (In the formula, X represents = O and R represents -O-CO-R 1 or -CHR 2 -R 3
(R 1 is a linear or branched alkyl group, a linear or branched alkenyl group, a linear or branched aralkyl group, or a substituted or unsubstituted phenyl group, R 2
Is a hydrogen atom or a linear or branched lower alkyl group, and R 3 is a linear or branched alkyl group, a linear or branched alkenyl group, a linear or branched alkoxy group, a linear or A branched alkenyloxy group, a straight chain or branched aralkyl group, or a substituted or unsubstituted phenyl group). Here, R is -CH (CH 3) (CH 2 ) 3 CH
It is never (CH 3 ) 2 . ) The compound shown by these.
JP11276093A 1993-05-14 1993-05-14 Steroid compounds Expired - Fee Related JP3584050B2 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004055039A1 (en) * 2002-12-18 2004-07-01 Unibioscreen S.A. Steroid compounds with anti-tumor activity
CN103214536A (en) * 2013-02-07 2013-07-24 中国人民解放军第二军医大学 Polyhydroxy steroidal compounds separated from coral, and application thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004055039A1 (en) * 2002-12-18 2004-07-01 Unibioscreen S.A. Steroid compounds with anti-tumor activity
CN103214536A (en) * 2013-02-07 2013-07-24 中国人民解放军第二军医大学 Polyhydroxy steroidal compounds separated from coral, and application thereof
CN103214536B (en) * 2013-02-07 2015-12-09 中国人民解放军第二军医大学 The polyhydroxysteroids compounds and application thereof that obtain is separated from coral

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