MLN-944, XR-5944, -Drug Synthesis Database

【结构式】

【药物名称】MLN-944, XR-5944

【化学名称】N,N'-(1,2-Ethanediy)bis(imino-2,1-ethanediyl)bis(9-methylphenazine-1-carboxamide)

【CA登记号】206531-58-0 (monohydrochloride)

【分子式】C₃₄H₃₄N₈O₂

【分子量】586.70248

【开发单位】Xenova (Originator), Millennium (Licensee)

【药理作用】Oncolytic Drugs, Solid Tumors Therapy, Antimitotic Drugs, DNA-Intercalating Drugs

合成路线1

Copper-catalyzed coupling of o-toluidine (I) with 2-bromo-3-nitrobenzoic acid (II) gave the N-aryl-3-nitroanthranilic acid (III). Reductive cyclization with NaBH4 in the presence NaOEt produced the desired phenazine (V) along with amino anthranilic acid (VI), which were separated by fractional crystallization. Carboxylic acid (V) was then activated as the imidazolide (VI) upon treatment with carbonyl diimidazole. Finally, coupling of triethylenetetramine (VII) with two equivalents of imidazolide (VI) produced the title diamide.

参考文献中间体

【1】 Rewcastle, G.W.; et al.; Potential antitumor agents. 51. Synthesis and antitumor activity of substituted phenazine-1-carboxamides. J Med Chem 1987, 30, 5, 843.
【2】 Denny, W.A.; Gamage, S.A.; Spicer, J.A.; Baguley, B.C.; Finlay, G.J. (Xenova Group plc); Bis(acridinecarboxamide) and bis(phenazinecarboxamide) as antitumour agents. EP 0934278; GB 2334032; WO 9817650 .

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)	15511	o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine	95-53-4	C₇H₉N	详情	详情
(II)	38776	2-bromo-3-nitrobenzoic acid		C₇H₄BrNO₄	详情	详情
(III)	38777	3-nitro-2-(2-toluidino)benzoic acid		C₁₄H₁₂N₂O₄	详情	详情
(V)	38778	9-methyl-1-phenazinecarboxylic acid		C₁₄H₁₀N₂O₂	详情	详情
(VI)	38779	3-amino-2-(2-toluidino)benzoic acid		C₁₄H₁₄N₂O₂	详情	详情
(VII)	38780	1H-imidazol-1-yl(9-methyl-1-phenazinyl)methanone		C₁₇H₁₂N₄O	详情	详情
(VIII)	38781	N-(2-aminoethyl)-N-[2-[(2-aminoethyl)amino]ethyl]amine; N(1),N(2)-bis(2-aminoethyl)-1,2-ethanediamine	112-24-3	C₆H₁₈N₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)