Levosimendan, (-)-OR-1259, Simdax, -Drug Synthesis Database

【结构式】

【药物名称】Levosimendan, (-)-OR-1259, Simdax

【化学名称】(R)-(-)-2-[4-(4-Methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenylhydrazono]propanedinitrile
　　　　　　(R)-(-)-2-[4-(4-Methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenylhydrazono]malonodinitrile
　　　　　　(R)-(-)-6-[4-(1,1-Dicyanomethylenehydrazino)phenyl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one

【CA登记号】141505-33-1, 131741-08-7 (racemate)

【分子式】C₁₄H₁₂N₆O

【分子量】280.29134

【开发单位】Orion Corp. (Originator), Abbott (Licensee)

【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Calcium Sensitizers, K(ATP) Channel Activators

合成路线1

The optical resolution of 6-(4-aminophenyl)-5-methyl-2,3,4,5-tetrahydropyridazin-3-one (I) with L-tartaric acid in isopropanol or D-tartaric acid in ethyl acetate gives the (R)-enantiomer (II), which is then condensed with malonodinitrile (III) by means of NaNO2 and HCl in cool water.

参考文献中间体

【1】 Haikala, H.O.; Nore, P.T.; Honkanen, E.J.; Pystynen, J.J.; Lonnberg, K.K.; Luiro, A.M.; Pippuri, A.K. (Orion Corporation); Heterocyclic cpds.. EP 0383449; JP 1990288868; US 5019575; US 5122524; US 5185332 .
【2】 Backstrom, R.J.; Haarala, J.V.; Honkanen, E.J.; Nore, P.T.; Wikberg, T.E.I.; Haikala, H.O. (Orion Corporation); Pyridazine deriv.. GB 2251615; JP 1994504275; US 5424428; US 5512571; US 5569657; WO 9212135 .
【3】 Tanninen, V.P.; Timmerbacka, M.; Kaukonen, J.; Lehtonen, J.; Hyppölä, R.; Muttonen, E. (Orion Corporation); Method for obtaining pure enantiomers of a pyridazinone deriv.. WO 9735841 .

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)	29204	6-(4-aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone		C₁₁H₁₃N₃O	详情	详情
(II)	37270	(5R)-6-(4-aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone		C₁₁H₁₃N₃O	详情	详情
(III)	12061	Malononitrile	109-77-3	C₃H₂N₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)