GL-579225, -Drug Synthesis Database

【结构式】

【药物名称】GL-579225

【化学名称】N,N'-Bis[5-[N-[2-(N1-methylamidino)ethyl]carbamoyl]-1-(3-methylbutyl)-1H-pyrrol-3-yl]benzene-1,4-dicarboxamide

【CA登记号】386251-89-4

【分子式】C₃₆H₅₂N₁₀O₄

【分子量】688.88044

【开发单位】Genelabs (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY

合成路线1 合成路线2

合成路线1

Alkylation of ethyl 4-nitropyrrole-2-carboxylate (I) with 3-methylbutyl bromide (II) in the presence of NaOMe affords the N-isoamyl pyrrole (III). Saponification of the ethyl ester group of (III), followed by treatment of the resultant carboxylic acid (IV) with SOCl2 provides acid chloride (V). This is subsequently coupled with 3-aminopropionitrile (VI) to yield the N-(2-cyanoethyl) amide (VII). Conversion of the cyano group of (VII) into the N-methyl amidine (VIII) is then accomplished under Pinner reaction conditions. Reduction of the nitro group of (VIII) by catalytic hydrogenation over Pd/C furnishes the intermediate aminopyrrole (IX).

参考文献中间体

【1】 Roberts, C.D.; Keicher, J.D.; Dyatkina, N.B.; et al.; Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetraamides are potent antibacterials against vancomycin resistant Enteroccoci and methicillin resistant Staphylococcus aureus. J Med Chem 2002, 45, 4, 805.
【2】 Dyatkina, N.; Hanson, E.; Liehr, S.; et al.; Synthesis, SAR and antimicrobial activity of pyrrole tetraamides. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 62.
【3】 Nelson, P.H.; Muchowski, J.M.; Dyatkina, N.B.; Shi, D.-F.; Zhang, W.; Liehr, S.J.R.; Velligan, M.D.; Botyanszki, J.; Roberts, C.D.; Khorlin, A. (Genelabs Technologies, Inc.); Novel cpds. possessing antibacterial, antifungal or antitumor activity. WO 0200650 .

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)	60988	1-methoxy-2,3-dihydro-1H-inden-2-yl methanesulfonate		C₁₁H₁₄O₄S	详情	详情
(II)	46234	1-bromo-3-methylbutane		C₅H₁₁Br	详情	详情
(III)	54019	ethyl 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylate		C₁₂H₁₈N₂O₄	详情	详情
(IV)	54020	1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid		C₁₀H₁₄N₂O₄	详情	详情
(V)	54021	1-isopentyl-4-nitro-1H-pyrrole-2-carbonyl chloride		C₁₀H₁₃ClN₂O₃	详情	详情
(VI)	38094	3-aminopropanenitrile	151-18-8	C₃H₆N₂	详情	详情
(VII)	54022	N-(2-cyanoethyl)-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide		C₁₃H₁₈N₄O₃	详情	详情
(VIII)	60999	N-[3-imino-3-(methylamino)propyl]-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide		C₁₄H₂₃N₅O₃	详情	详情
(IX)	61000	4-amino-N-[3-imino-3-(methylamino)propyl]-1-isopentyl-1H-pyrrole-2-carboxamide		C₁₄H₂₅N₅O	详情	详情

合成路线2

Treatment of terephthalic acid (X) with pentafluorophenyl trifluoroacetate gives rise to the bis-pentafluorophenyl ester (XI). Then, coupling of the active ester (XI) with aminopyrrole (IX) in hot DMF yields the title terephthalic diamide.

参考文献中间体

【1】 Roberts, C.D.; Keicher, J.D.; Dyatkina, N.B.; et al.; Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetraamides are potent antibacterials against vancomycin resistant Enteroccoci and methicillin resistant Staphylococcus aureus. J Med Chem 2002, 45, 4, 805.
【2】 Dyatkina, N.; Hanson, E.; Liehr, S.; et al.; Synthesis, SAR and antimicrobial activity of pyrrole tetraamides. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 62.

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)	54026	Trifluoroacetic acid pentafluorophenylester	14533-84-7	C₈F₈O₂	详情	详情
(IX)	61000	4-amino-N-[3-imino-3-(methylamino)propyl]-1-isopentyl-1H-pyrrole-2-carboxamide		C₁₄H₂₅N₅O	详情	详情
(X)	54025	1,4-Benzenedicarboxylic acid; Benzene-1,4-dicarboxylic acid; p-Benzenedicarboxylic acid; p-Phthalic acid; Terephthalic acid	100-21-0	C₈H₆O₄	详情	详情
(XI)	54027	bis(2,3,4,5,6-pentafluorophenyl) terephthalate		C₂₀H₄F₁₀O₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)