GPI-1511, -Drug Synthesis Database

【结构式】

【药物名称】GPI-1511

【化学名称】1-(3,3-Dimethyl-2-oxopentanoyl)piperidine-2(S)-carbothioic acid S-(3,3-diphenylpropyl) ester

【CA登记号】252770-39-1, 205388-57-4 (undefined stereoch.)

【分子式】C₂₈H₃₅NO₃S

【分子量】465.66005

【开发单位】Guilford Pharmaceuticals (Originator)

【药理作用】Alzheimer's Dementia, Treatment of , Antiparkinsonian Drugs, Cerebrovascular Diseases, Treatment of, Cognition Disorders, Treatment of, Extrapyramidal Disorders, Treatment of, Immunologic Neuromuscular Disorders, Treatment of, Multiple Sclerosis, Agents for, NEUROLOGIC DRUGS, Stroke, Treatment of, Neurotrophic Agents, Rotamase (FKBP12) Inhibitors

合成路线1 合成路线2

合成路线1

Acylation of methyl pipecolinate (I) with methyl oxalyl chloride (II) provides oxamate (III). Subsequent addition of 1,1-dimethylpropylmagnesium chloride (IV) to oxamate (III) gives rise to keto amide (V). The methyl ester group of (V) is then hydrolyzed by means of LiOH, yielding the intermediate carboxylic acid (VI)

参考文献中间体

【1】 Hamilton, G.S.; Wu, Y.-Q.; Limburg, D.C.; Wilkinson, D.E.; Vaal ,M.J.; Li, J.-H.; Thomas, C.; Huang, W.; Sauer, H.; Ross, D.T.; Soni, R.; Chen, Y.; Guo, H.; Howorth, P.; Valentine, H.; Liang, S.; Spicer, D.; Fuller, M.; Steiner, J.P; Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects. J Med Chem 2002, 45, 16, 3549.

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)	25354	methyl (2S)-2-piperidinecarboxylate		C₇H₁₃NO₂	详情	详情
(II)	26971	2-methoxy-2-oxoacetyl chloride	5781-53-3	C₃H₃ClO₃	详情	详情
(III)	60287	methyl 1-[2-(methyloxy)-2-oxoacetyl]-2-piperidinecarboxylate		C₁₀H₁₅NO₅	详情	详情
(IV)	60288	chloro(1,1-dimethylpropyl)magnesium		C₅H₁₁ClMg	详情	详情
(V)	60289	methyl 1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidinecarboxylate		C₁₄H₂₃NO₄	详情	详情
(VI)	60290	1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidinecarboxylic acid		C₁₃H₂₁NO₄	详情	详情

合成路线2

3,3-Diphenyl-1-propanol (VII) is converted into the corresponding alkyl bromide (VIII) by treatment with CBr4 and PPh3. Reaction of bromide (VIII) with thiourea provides the isothiouronium salt (IX), which is further hydrolyzed to thiol (X) under alkaline conditions. Finally, acylation of thiol (X) with carboxylic acid (VI) by means of DCC yields the target thioester

参考文献中间体

【1】 Hamilton, G.S.; Wu, Y.-Q.; Limburg, D.C.; Wilkinson, D.E.; Vaal ,M.J.; Li, J.-H.; Thomas, C.; Huang, W.; Sauer, H.; Ross, D.T.; Soni, R.; Chen, Y.; Guo, H.; Howorth, P.; Valentine, H.; Liang, S.; Spicer, D.; Fuller, M.; Steiner, J.P; Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects. J Med Chem 2002, 45, 16, 3549.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	60290	1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidinecarboxylic acid	C₁₃H₂₁NO₄	详情	详情
(VII)	60291	3,3-diphenyl-1-propanol	C₁₅H₁₆O	详情	详情
(VIII)	60292	1-(3-bromo-1-phenylpropyl)benzene	C₁₅H₁₅Br	详情	详情
(IX)	60293		C₁₆H₁₈N₂S	详情	详情
(X)	30783	3,3-diphenyl-1-propanethiol; 3,3-diphenylpropylhydrosulfide	C₁₅H₁₆S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)