Gastrazole, JB-95008
5-[N-[5-[N-(环甲基)氨甲酰]-1H-苯并咪唑-6-酰羰基]-2-氟-L-苯基醛胺基]异邻苯二甲酸Chemical Name: 5-[N-[5-[N-(Cycloheptylmethyl)carbamoyl]-1H-benzimidazol-6-ylcarbonyl]-2-fluoro-L-phenylalanylamino]isophthalic acid
CAS No. 174610-98-1
项目整合开发状态: Phase II
项目研究机构: James Black Foundation (Originator), Johnson & Johnson (Originator)
合成路线:5-Nitroisophthalic acid (I) is converted into the dibenzyl ester (II) via activation with SOCl2.After nitro group reduction in (II),the resultant amine (III) is coupled with N-Boc-L-2-fluorophenylalanine (IV) by means of PyBrOP and DIEA to furnish amide (V).Subsequent acidic cleavage of the N-Boc protecting group of (V) provides amine (VI).(1)
合成路线:Thermal dehydration of benzimidazole-5,6-dicarboxylic acid (VII) provides the cyclic anhydride (VIII).Subsequent condensation of (VIII) with amine (VI) leads to the amido-acid (IX),which is further coupled to cycloheptylmethylamine (X),yielding the benzimidazole dicarboxamide (XI).Finally,catalytic hydrogenolysis of the benzyl ester groups of (XI) affords the target isophthalic acid derivative.(1,2)
📌 参考资料/链接：
参考文献标题:Gastrin and CCK receptor ligands
文献作者:Kalindjian,S.B.; Steel,K.I.M.; Pether,M.J.; Davies,J.M.R.; Low,C.M.R.; Hudson,M.L.; Buck,I.M.; McDonald,I.M.; Dunstone,D.J.; Tozer,M.J.(James Black Foundation Ltd.)
参考来源:EP 0720601; EP 0763026; GB 2290539; JP 1997502430; JP 1998504525; US 5795907; US 5912260; US 5919829; WO 9504720; WO 9532949
📄 详细内容
合成路线:Thermal dehydration of benzimidazole-5,6-dicarboxylic acid (VII) provides the cyclic anhydride (VIII).Subsequent condensation of (VIII) with amine (VI) leads to the amido-acid (IX),which is further coupled to cycloheptylmethylamine (X),yielding the benzimidazole dicarboxamide (XI).Finally,catalytic hydrogenolysis of the benzyl ester groups of (XI) affords the target isophthalic acid derivative.(1,2)
参考文献标题:Non-peptide cholecystokinin-B/gastric receptor antagonists based on bicyclic,heteroaromatic skeletons
文献作者:Kalindjian,S.B.; Buck,I.M.; Davies,J.M.R.; Dunstone,D.J.; Hudson,M.L.; Low,C.M.R.; McDonald,I.M.; Pether,M.J.; Steel,K.I.M.; Tozer,M.J.; Vinter,J.G.
参考来源:J Med Chem 1996,39(9),1806
产品链接: CAS No. 174610-98-1››