Methylnaltrexone bromide, MRZ-2663BR, Relistor, -Drug Synthesis Database

【结构式】

【药物名称】Methylnaltrexone bromide, MRZ-2663BR, Relistor

【化学名称】17-(Cyclopropylmethyl)-4,5alpha-epoxy-3,14-dihydroxy-17-methyl-6-oxomorphinanium bromide
　　　　　　N-Methylnaltrexone bromide

【CA登记号】73232-52-7, 83387-25-1 (cation), 73232-53-8 (iodide), 125292-47-9 (racemate)

【分子式】C₂₁H₂₆BrNO₄

【分子量】436.34967

【开发单位】Mallinckrodt (Supplier), University of Chicago (Originator), Progenics (Licensee)

【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Constipation, Agents for, GASTROINTESTINAL DRUGS, Nausea and Vomiting, Treatment of, NEUROLOGIC DRUGS, Opioid Antagonists

合成路线1 合成路线2 合成路线3

合成路线1

By quaternization of N-(cyclopropylmethyl)noroxymorphone (I) with methyl bromide in acetone/DMF.

参考文献中间体

【1】 Goldberg, L.I.; Stockhaus, K.; Merz, H. (Boehringer Ingelheim GmbH); Quaternary derivs. of noroxymorphone which relieve intestinal immobility. US 4176186 .

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)	37822	(1S,5R,13R,17R)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one		C₂₀H₂₃NO₄	详情	详情

合成路线2

参考文献中间体

【1】 Dlubala A. 2008. Process for preparing N-alkylnaltrexone halides. WO 2008034973.
【2】 Ninan A, Sainsbury M. 1993. An improved synthesis of noroxymorphone. Tetrahedron, 48(32): 6709～6716.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	67277	(4S,4aR,7aR,12bR)-4a,9-dihydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one hydrochloride	C₁₆H₁₇NO₄.HCl	详情	详情
(II)	37822	(1S,5R,13R,17R)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one	C₂₀H₂₃NO₄	详情	详情
(III)	67278	(4S,4aR,7aS,12bR)-9-(benzyloxy)-3-(cyclopropylmethyl)-4a-hydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one	C₂₇H₃₀NO₄	详情	详情
(IV)	67279	(4S,4aR,7aS,12bR)-9-(benzyloxy)-3-(cyclopropylmethyl)-4a-hydroxy-3-methyl-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium	C₂₈H₃₂NO₄	详情	详情
(V)	67280	(4S,4aR,7aS,12bR)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium	C₂₁H₂₆NO₄	详情	详情
(VI)	67281	(4S,4aR,7aS,12bR)-3-(cyclopropylmethyl)-4a-hydroxy-3-methyl-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-9-olate	C₂₁H₂₅NO₄	详情	详情
(VII)	67282	(4S,4aR,7aS,12bR)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium bromide	C₂₁H₂₇BrNO₄	详情	详情

合成路线3

参考文献中间体

【1】 Doshan HD, Perez J. 2006. Synthesis of (R)-N-methylnaltrexone. WO 2006127899.

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)	25079	(1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one; Naltrexone	16590-41-3	C₂₀H₂₃NO₄	详情	详情
(II)	67283	(4S,4aR,7aS,12bR)-3-(cyclopropylmethyl)-4a-hydroxy-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl isobutyrate		C₂₄H₂₉NO₅	详情	详情
(III)	67284	(4S,4aR,7aS,12bR)-3-(cyclopropylmethyl)-4a-hydroxy-9-(isobutyryloxy)-3-methyl-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium iodide		C₂₅H₃₂INO₅	详情	详情
(IV)	67282	(4S,4aR,7aS,12bR)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium bromide		C₂₁H₂₇BrNO₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)