Tegaserod maleate, HTF-919, SDZ-HTF-919, Zelnorm, Zelmac, -Drug Synthesis Database

【结构式】

【药物名称】Tegaserod maleate, HTF-919, SDZ-HTF-919, Zelnorm, Zelmac

【化学名称】2-[(5-Methoxy-1H-indol-3-yl)methylene]-N-pentylhydrazinecarboximidamide monomaleate
　　　　　　1-(5-Methoxy-1H-indol-3-ylmethyleneamino)-3-pentylguanidine monomaleate

【CA登记号】189188-57-6, 145158-71-0 (free base)

【分子式】C₂₀H₂₇N₅O₅

【分子量】417.46869

【开发单位】Novartis (Originator), Bristol-Myers Squibb (Codevelopment)

【药理作用】Constipation, Agents for, Esophageal Diseases, Treatment of, Gastric Emptying Disorders,Treatment of of, Gastroesophageal Reflux Disease, Agents for, GASTROINTESTINAL DRUGS, Irritable Bowel Syndrome, Agents for, Non-Ulcer Dyspepsia, Agents for, Prokinetic Agents, 5-HT4 Partial Agonists

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

参考文献中间体

【1】 Sundaram V, Gudipati S. Brahmeswararao Mandava VN, et al. 2006. Process for preparing highly pure tegaserod and tegaserod maleate. US 2006178519

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)	20318	methyl 1-hydrazinecarbimidothioate hydroiodide		C₂H₇N₃S.HI	详情	详情
(II)	20320	N-pentyl-1-hydrazinecarboximidamide hydroiodide		C₆H₁₆N₄.HI	详情	详情
(III)	20321	5-methoxy-1H-indole-3-carbaldehyde	10601-19-1	C₁₀H₉NO₂	详情	详情

合成路线2

参考文献中间体

【1】宗在伟，魏佳．2006.一种替加色罗的制备方法，发明专利申请公开说明书，CN 1869021

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)	20321	5-methoxy-1H-indole-3-carbaldehyde	10601-19-1	C₁₀H₉NO₂	详情	详情
(II)	48868	ethyl 1-hydrazinecarbimidothioate		C₃H₉N₃S	详情	详情
(III)	66762	(E)-ethyl 2-((5-methoxy-1H-indol-3-yl)methylene)hydrazinecarbimidothioate		C₁₃H₁₆N₄OS	详情	详情

合成路线3

参考文献中间体

【1】 Buchheit KH, Gamse R, Giger R, et al. 1995. The serotonin 5-HT₄ receptor. 2. structure-ractivity studies of the indole carbazimidamide class 0f agonists. J Med Chan, 38(13): 2331～2338

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)	12954	1-Hydrazinecarbothioamide; Thiosemicarbazide	79-19-6	CH₅N₃S	详情	详情
(II)	20318	methyl 1-hydrazinecarbimidothioate hydroiodide		C₂H₇N₃S.HI	详情	详情
(IX)	20321	5-methoxy-1H-indole-3-carbaldehyde	10601-19-1	C₁₀H₉NO₂	详情	详情
(III)	15764	amylamine; 1-pentanamine; pentylamine	110-58-7	C₅H₁₃N	详情	详情
(IV)	20320	N-pentyl-1-hydrazinecarboximidamide hydroiodide		C₆H₁₆N₄.HI	详情	详情
(V)	66763	3-methyl-4-nitrophenol;4-Nitro-m-cresol	2581-34-2	C₇H₇NO₃	详情	详情
(VI)	66764	4-methoxy-2-methyl-1-nitrobenzene;3-Methyl-4-nitroanisole;5-Methoxy-2-nitrotoluene	5367-32-8	C₈H₉NO₃	详情	详情
(VII)	66765	(E)-2-(5-methoxy-2-nitrophenyl)-N,N-dimethylethenamine		C₁₁H₁₄N₂O₃	详情	详情
(VIII)	25902	1H-Indol-5-yl methyl ether; 5-Methoxy-1H-indole; 5-Methoxyindole	1006-94-6	C₉H₉NO	详情	详情

合成路线4

参考文献中间体

【1】 Ge YH. Wu YM, Xue ZJ．et al. 2004. Synthesis of 5-methoocyindole-3-carboxaldehyde. 化工时刊．18(7)：24～25
【2】 Teng X, Degterev A, Jagtap P, et al. 2005. Structure-activity relationship study of nove necroptosis inhibitors. Bioorg Med Chem lett, 15(22) : 5039～5044

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)	66766	4-nitroanisole;1-Methoxy-4-nitrobenzene;4-Methoxy-1-nitrobenzene;4-Methoxynitrobenzene;4-Nitro-1-methoxybenzene;4-Nitroanisole;4-Nitromethoxybenzene;4-Nitrophenyl methyl ether;Methyl 4-nitrophenyl ether;Methyl p-nitrophenyl ether;p-Methoxynitrobenzene;p-Nitroanisole;p-Nitrobenzene methyl ether;p-Nitromethoxybenzene	100-17-4	C₇H₇NO₃	详情	详情
(II)	25902	1H-Indol-5-yl methyl ether; 5-Methoxy-1H-indole; 5-Methoxyindole	1006-94-6	C₉H₉NO	详情	详情
(III)	20321	5-methoxy-1H-indole-3-carbaldehyde	10601-19-1	C₁₀H₉NO₂	详情	详情

合成路线5

The alkylation of thiosemicarbazide (I) with methyl iodide in hot ethanol gives the corresponding S-methyl derivative (II), which is treated with pentylamine (III) in refluxing methanol to yield N1-amino-N3-pentylguanidine hydroiodide (IV). Finally, this compound is condensed with 5-methoxy-1H-indole-3-carbaldehyde (V) by means of HCl in methanol.

参考文献中间体

【1】 Pfannkuche, H.-J.; Hoyer, D.; Mattes, H.; Klein, F.; Giger, R.; Gamse, R.; Kloppner, E.; Buchheit, K.-H.; The serotonin 5-HT4 receptor. 2. Structure-activity studies of the indole carbazimidamide class of agonists. J Med Chem 1995, 38, 13, 2331.
【2】 Silvestre, J.S.; Graul, A.; Castañer, J.; Tegaserod Maleate . Drugs Fut 1999, 24, 1, 38.
【3】 Giger, R. K. A.; Mattes, H. (Novartis AG; Novartis Deutschland GmbH); Aminoguanidines. EP 0505322; US 5510353 .

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)	12954	1-Hydrazinecarbothioamide; Thiosemicarbazide	79-19-6	CH₅N₃S	详情	详情
(II)	20318	methyl 1-hydrazinecarbimidothioate hydroiodide		C₂H₇N₃S.HI	详情	详情
(III)	15764	amylamine; 1-pentanamine; pentylamine	110-58-7	C₅H₁₃N	详情	详情
(IV)	20320	N-pentyl-1-hydrazinecarboximidamide hydroiodide		C₆H₁₆N₄.HI	详情	详情
(V)	20321	5-methoxy-1H-indole-3-carbaldehyde	10601-19-1	C₁₀H₉NO₂	详情	详情

Extended Information