Posatirelin, pAad-Leu-Pro-NH2, RGH-2202, Pyladox, -Drug Synthesis Database

【结构式】

【药物名称】Posatirelin, pAad-Leu-Pro-NH2, RGH-2202, Pyladox

【化学名称】N-[6-Oxopiperidin-2(S)-ylcarbonyl]-L-leucyl-L-prolinamide

【CA登记号】78664-73-0

【分子式】C₁₇H₂₈N₄O₄

【分子量】352.43711

【开发单位】Gedeon Richter (Originator), Dainippon Pharmaceutical (Licensee)

【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, TRH Analogs

合成路线1 合成路线2

合成路线1

a) N-Protected L-Leucine activated as the pentafluorophenyl ester (I) is coupled with L-prolinamide (II), and the resulting dipeptide (III) is deprotected te (IV) and coupled with L-pyro-2-aminoadipic acid pentatluorophenyl ester (V) to give RGH-2202.

参考文献中间体

【1】 Kisfaludy, L.; Szporny, L.; Pálosi, É.; Szirtes, T.; Synthesis of thyrotropin-releasing hormone analogu. J Med Chem 1986, 29, 1654.
【2】 Szirtes, T.; Szporny, L.; Pálosi, É.; Kisfaludy, L.; Synthesis of thyrotropin releasing hormone analogu. J Med Chem 1984, 27, 741.
【3】 Nogradi, M.; RGH-2202. Drugs Fut 1988, 13, 5, 420.

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)	22653	2,3,4,5,6-pentafluorophenyl 2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoate		C₂₀H₁₈F₅NO₄	详情	详情
(II)	22654	2-pyrrolidinecarboxamide	2812-47-7	C₅H₁₀N₂O	详情	详情
(III)	22655	benzyl 1-[[2-(aminocarbonyl)-1-pyrrolidinyl]carbonyl]-3-methylbutylcarbamate		C₁₉H₂₇N₃O₄	详情	详情
(IV)	22656	1-[2-(aminocarbonyl)-1-pyrrolidinyl]-4-methyl-1-oxo-2-pentanaminium chloride		C₁₁H₂₂ClN₃O₂	详情	详情
(V)	22657	2,3,4,5,6-pentafluorophenyl (2S)-6-oxo-2-piperidinecarboxylate		C₁₂H₈F₅NO₃	详情	详情

合成路线2

b) Large scale preparation of L-pyro-2-aminoadipic acid (IX) is accomplished by oxidation of the N-protected L-lysine derivative (VI) with KMnO4 followed by deprotection to (VIII) and cyclization.

参考文献中间体

【1】 Szirtes, T.; Szporny, L.; Pálosi, É.; Kisfaludy, L.; Synthesis of thyrotropin releasing hormone analogu. J Med Chem 1984, 27, 741.
【2】 Kisfaludy, L.; Szporny, L.; Pálosi, É.; Szirtes, T.; Synthesis of thyrotropin-releasing hormone analogu. J Med Chem 1986, 29, 1654.
【3】 Nogradi, M.; RGH-2202. Drugs Fut 1988, 13, 5, 420.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	22662	2,3,4,5,6-pentafluorophenol	771-61-9	C₆HF₅O	详情	详情
(V)	22656	1-[2-(aminocarbonyl)-1-pyrrolidinyl]-4-methyl-1-oxo-2-pentanaminium chloride		C₁₁H₂₂ClN₃O₂	详情	详情
(VI)	22658	N(6)-[(benzyloxy)carbonyl]lysine		C₁₄H₂₀N₂O₄	详情	详情
(VII)	22659	N(6)-[(benzyloxy)carbonyl]-6-oxolysine		C₁₄H₁₈N₂O₅	详情	详情
(VIII)	22660	2-aminohexanedioic acid		C₆H₁₁NO₄	详情	详情
(IX)	22661	(2S)-6-oxo-2-piperidinecarboxylic acid		C₆H₉NO₃	详情	详情

Extended Information