FK-888
(2S,4R)-4-羟基-1-(1-甲基吲哚-3-羰基)-N-[(2S)-1-(甲基-(苯基甲基)氨基)-3-萘-2-基-1-氧代丙烷-2-基]吡咯烷-2-甲酰胺Chemical Name: 1-Methylindol-3-ylcarbonyl-[4(R)-hydroxy]-L-prolyl-[3-(2-naphthyl)]-L-alanine N-benzyl-N-methylamide
CAS No. 138449-07-7
项目整合开发状态: Phase II
项目研究机构: Fujisawa (Originator)
合成路线:The protection of the amino group of L-(2-naphthyl)alanine (I) with di-tert-butyl dicarbonate and triethylamine gives N-tert-butoxycarbonyl-L-(2-naphthyl)alanine (II),which is amidated with benzylmethylamine by means of hydroxybenzotriazole (HOBT) and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (WSC) in dichloromethane yielding N-tert-butoxycarbonyl-L-(2-naphthyl)alanine N-benzyl-N-methylamide (III).Elimination of the tert-butoxycarbonyl group of (III) with HCl in dioxane affords L-(2-naphthyl)alanine N-benzyl-N-methylamide (IV),which is condensed with N-(tert-butoxycarbonyl)-[4(R)-hydroxy]-L-proline (V) by means of HOBT an WSC as before giving the protected dipeptide (VI).Elimination of the protecting group of (VI) with HCl in dioxane as before yields the dipeptide (VII) with the free amino group,which is finally acylated with 1-methylindole-3-carboxylic acid (VIII) by means of HOBT and WSC as before.
📌 参考资料/链接：
参考文献标题:Peptides having tachykinin antagonist activity,a process for preparation thereof and pharmaceutical compsns.comprising the same
文献作者:Matsuo,M.; Hagiwara,D.; Miyake,H.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:EP 0443132; JP 1992210996; US 5468731
📄 详细内容
合成路线:The protection of the amino group of L-(2-naphthyl)alanine (I) with di-tert-butyl dicarbonate and triethylamine gives N-tert-butoxycarbonyl-L-(2-naphthyl)alanine (II),which is amidated with benzylmethylamine by means of hydroxybenzotriazole (HOBT) and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (WSC) in dichloromethane yielding N-tert-butoxycarbonyl-L-(2-naphthyl)alanine N-benzyl-N-methylamide (III).Elimination of the tert-butoxycarbonyl group of (III) with HCl in dioxane affords L-(2-naphthyl)alanine N-benzyl-N-methylamide (IV),which is condensed with N-(tert-butoxycarbonyl)-[4(R)-hydroxy]-L-proline (V) by means of HOBT an WSC as before giving the protected dipeptide (VI).Elimination of the protecting group of (VI) with HCl in dioxane as before yields the dipeptide (VII) with the free amino group,which is finally acylated with 1-methylindole-3-carboxylic acid (VIII) by means of HOBT and WSC as before.
参考文献标题:Studies on neurokinin antagonists.4.Synthesis and structure-activity relationships of novel dipeptide substance P antagonists
文献作者:Hagiwara,D.; Miyake,H.; Igari,N.; Karino,M.; Maeda,Y.; Fujii,T.; Matsuo,M.
参考来源:J Med Chem 1994,37(13),2090-9
合成路线:The protection of the amino group of L-(2-naphthyl)alanine (I) with di-tert-butyl dicarbonate and triethylamine gives N-tert-butoxycarbonyl-L-(2-naphthyl)alanine (II),which is amidated with benzylmethylamine by means of hydroxybenzotriazole (HOBT) and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (WSC) in dichloromethane yielding N-tert-butoxycarbonyl-L-(2-naphthyl)alanine N-benzyl-N-methylamide (III).Elimination of the tert-butoxycarbonyl group of (III) with HCl in dioxane affords L-(2-naphthyl)alanine N-benzyl-N-methylamide (IV),which is condensed with N-(tert-butoxycarbonyl)-[4(R)-hydroxy]-L-proline (V) by means of HOBT an WSC as before giving the protected dipeptide (VI).Elimination of the protecting group of (VI) with HCl in dioxane as before yields the dipeptide (VII) with the free amino group,which is finally acylated with 1-methylindole-3-carboxylic acid (VIII) by means of HOBT and WSC as before.
参考文献标题:FK-888
文献作者:Leeson,P.A.; Rabasseda,X.; Castar,J.
参考来源:Drugs Fut 1997,22(4),353
产品链接: CAS No. 138449-07-7››