CAS: 629652-42-2; Methyl (1S,3S)-1-(Benzo[d][1,3]Dioxol-5-yl)-2-(2-Chloroacetyl)-2,3,4,9-Tetrahydro-1H-Pyrido[3,4-B]Indole-3-Carboxylate

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chloroacetyl chloride (1S,3S)-1-(3,4-methylenedioxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester piperonal L-tryptophan methyl ester (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1′,2':1,6]-pyrido[3,4-b]indole-1,4-dione

📜甲基色氨酸置于碳酸氢钠,三氟乙酸体系中,用 二氯甲烷,氯仿 作为反应溶剂,化学反应 25.0H,反应生成 (1S,3S)-1-(1,3-苯并二氧戊环-5-基)-2-(2-氯乙酰基)-2,3,4,9-四氢-1H-吡啶并[3,4-B]吲哚-3-羧酸甲酯
参考文献:The Discovery Of Tadalafil: A Novel And Highly Selective Pde5 Inhibitor. 2: 2,3,6,7,12,12A-Hexahydropyrazino[1',2':1,6]Pyrido[3,4-B]Indole-1,4-Dione Analogues
标题:The Discovery Of Tadalafil: A Novel And Highly Selective Pde5 Inhibitor. 2: 2,3,6,7,12,12A-Hexahydropyrazino[1',2':1,6]Pyrido[3,4-B]Indole-1,4-Dione Analogues
摘要:Modification Of The Hydantoin Ring In The Previously Described Lead Compound 2A Has Led To The Discovery Of Compound 12A,Tadalafil,A Highly Potent And Highly Selective Pde5 Inhibitor. The Replacement Of The Hydantoin In Compound 2A By A Piperazinedione Ring Led To Compound Cis-11A Which Showed Similar Pde5 Inhibitory Potency. Introduction Of A 3,4-Methylenedioxy Substitution On The Phenyl Ring In Position 6 Led To A Potent Pde5 Inhibitor Cis-11C With Increased Cellular Potency. Optimization Of The Chain On The Piperazinedione Ring Led To The Identification Of The Racemic Cis-N-Methyl Derivative 11I. High Diastereospecificity For Pde5 Inhibition Was Observed In The Piperazinedione Series With The Cis-(6R,12Ar) Enantiomer Displaying The Highest Pde5 Inhibitory Activity. The Piperazinedione 12A,Tadalafil (Gf196960),Has Been Identified As A Highly Potent Pde5 Inhibitor (Ic50 = 5 Nm) With High Selectivity For Pde5 Vs Pde1-4 And Pde6. Compound 12A Displays 85-Fold Greater Selectivity Vs Pde6 Than Sildenafil 1.12A Showed Profound And Long-Lasting Blood Pressure Lowering Activity (30 Mmhg/> 7 H) In The Spontaneously Hypertensive Rat Model After Oral Administration (5 Mg/kg).
DOI:10.1021/jm0300577