Mifepristone, C-1073, CI-1073, RU-486, RU-38486, Mifeprex, Mifegyne, -Drug Synthesis Database

【结构式】

【药物名称】Mifepristone, C-1073, CI-1073, RU-486, RU-38486, Mifeprex, Mifegyne

【化学名称】11beta-(4-Dimethylaminophenyl)-17beta-hydroxy-17alpha-(1-propynyl)estra-4,9-dien-3-one

【CA登记号】84371-65-3（Chiral）;84371-65-3

【分子式】C₂₉H₃₅NO₂

【分子量】429.6078

【开发单位】Aventis Pharma (Originator), National Institutes of Health (Not Determined), Kosan (Marketer), Danco (Licensee), Population Council (Licensee)

【药理作用】Abortifacients, Adrenocortical Dysfunction Therapy, Anxiolytics, Bipolar Disorder, Treatment of, Cushing's Syndrome, Agents for, ENDOCRINE DRUGS, Gynecological Disorders, Treatment of , Mood Disorders, Treatment of, Posttraumatic Stress Disorder (PTSD), Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Glucocorticoid Receptor Antagonists, Progesterone Receptor Antagonists

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

参考文献中间体

【1】 Neef G.Beier S,Elger W, et aL 1984. New steroids with antiprogestational and antiglucocorticoid activities Steroids, 44 (4): 349～372
【2】 Wiechert R.Ned G 1987. Synthesis of antiprogestational steroids. J Steroid Biochem, 27 (4-6): 851～858

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	66526	13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[5,10-epoxycyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol		C₂₀H₂₈O₄	详情	详情
(II)	10863	Bromo[4-(dimethylamino)phenyl]magnesium	7353-91-5	C₈H₁₀BrMgN	详情	详情
(III)	66527	11-(4-(dimethylamino)phenyl)-13-methyl-1,2,4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolane]-5,17-diol		C₂₈H₃₉NO₄	详情	详情
(IV)	66528	11-(4-(dimethylamino)phenyl)-5-hydroxy-13-methyl-1,2,5,6,7,8,11,12,13,14,15,16-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17(4H)-one		C₂₈H₃₇NO₄	详情	详情
(V)	66529			C₂₈H₃₇NO₄	详情	详情
(VI)	43835	2-propynyl tetrahydro-2H-pyran-2-yl ether; 2-(2-propynyloxy)tetrahydro-2H-pyran	6089-04-9	C₈H₁₂O₂	详情	详情
(VII)	66530	11-(4-(dimethylamino)phenyl)-13-methyl-17-(3-((tetrahydro-2H-pyran-2-yl)oxy)prop-1-yn-1-yl)-1,2,4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolane]-5,17-diol		C₃₆H₄₉NO₆	详情	详情

合成路线2

参考文献中间体

【1】 Rao PN. 2000. A practical large-scale synthesis of 17 alpha-acetoxy-ll beta-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914). Steroids, 65 (7): 395～400

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	40864			C₂₁H₂₇NO₃	详情	详情
(II)	40866			C₂₄H₃₄ClNO₃Si	详情	详情
(III)	40867	(13S,17R)-17-acetyl-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	14340-01-3	C₂₀H₂₆O₃	详情	详情
(IV)	40868			C₂₄H₃₄O₅	详情	详情
(V)	40869			C₂₄H₃₄O₆	详情	详情
(VI)	10863	Bromo[4-(dimethylamino)phenyl]magnesium	7353-91-5	C₈H₁₀BrMgN	详情	详情
(VII)	40870			C₃₂H₄₅NO₆	详情	详情

合成路线3

参考文献中间体

【1】 Kim HK.1997. 21-Substituted progesterone derivatwes as new antiprogestational agents. W0 1997041145(本专利为US Department of Health & Human Servicres所有）

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	40864			C₂₁H₂₇NO₃	详情	详情
(II)	41669			C₂₄H₃₄BrNO₃Si	详情	详情
(III)	66531			C₂₀H₂₅BrO₃	详情	详情
(IV)	66532			C₂₂H₂₈O₅	详情	详情
(V)	66533			C₂₀H₂₆O₄	详情	详情
(VI)	41673			C₂₄H₃₄O₆	详情	详情
(VII)	41674			C₂₅H₃₆O₆	详情	详情
(VIII)	41675			C₂₅H₃₆O₇	详情	详情
(IX)	10863	Bromo[4-(dimethylamino)phenyl]magnesium	7353-91-5	C₈H₁₀BrMgN	详情	详情
(X)	41676			C₃₃H₄₇NO₇	详情	详情

合成路线4

The reaction of 3,3-(ethylenedioxy)estra-5(10),9(11)-diene-17(beta)-one (I) with propynylmagnesium bromine (II) in THF gives 3,3-(ethylenedioxy)-17(beta)-(propyn-1-yl)estra-5(10),9(11)-diene-17(beta)-ol (III), which is epoxidized with H2O2 in hexafluoroacetone-methylene chloride yielding 3,3-(ethylenedioxy)-17(beta)-(propyn-1-yl)-5(alpha),10(alpha)-epoxyestra-9(11)-en-17(beta)-ol (IV). The reaction of (IV) with 4-dimethylaminophenylmagnesium bromide (V) in THF affords 11(beta)-(4-dimethylaminophenyl)-3,3-(ethylenedioxy)-17(beta)-(propyn-1-yl)estra-9-en-17(beta)-ol (VI), which is finally deprotected by a treatment with HCl in metnanol.

参考文献中间体

【1】 Teutsch, J.G.; Costerousse, G.; Philibert, D.; Deraedt, R. (Aventis Pharma SA); Steroid. derivs. 11beta-substd.. FR 2497807; JP 1989279897; US 4447424; US 4978657; US 5043332 .
【2】 Kottegoda, S.R.; Castaner, J.; Serradell, M.N.; Adaikan, P.G.; RU-486. Drugs Fut 1984, 9, 10, 755.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	30502	3,3-Ethylenedioxyestra-5(10),9(11)-dien-17-one	5571-36-8	C₂₀H₂₆O₃	详情	详情
(II)	30503	bromo(1-propynyl)magnesium		C₃H₃BrMg	详情	详情
(III)	30504	3,3-(Ethylenedioxy)-17alpha-(1-propynyl)estra-5(10),9(11)-dien-17-beta-ol		C₂₃H₃₀O₃	详情	详情
(IV)	30505	5alpha,10alpha-Epoxy-3,3-(ethylenedioxy)-17alpha-(1-propynyl)estra-9(11)-en-17-beta-ol		C₂₃H₃₀O₄	详情	详情
(V)	10863	Bromo[4-(dimethylamino)phenyl]magnesium	7353-91-5	C₈H₁₀BrMgN	详情	详情
(VI)	30506	11beta-[4-(Dimethylamino)phenyl]-3,3-(ethylenedioxy)-17alpha-(1-propynyl)estra-4,9-diien-17-beta-ol		C₃₁H₃₉NO₃	详情	详情

Extended Information