GW-627368X
GW627368X抑制剂Chemical Name: N-[2-[4-(4,9-Diethoxy-1-oxo-2,3-dihydro-1H-benzo[f]isoindol-2-yl)phenyl]acetyl]benzenesulfonamide; 2-[4-(4,9-Diethoxy-1-oxo-2,3-dihydro-1H-benzo[f]isoindol-2-yl)phenyl]-N-(phenylsulfonyl)acetamide
CAS No. 439288-66-1
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Claisen condensation between diethyl phthalate (I) and diethyl succinate (II) in the presence of NaOEt gives rise to the naphthalenedicarboxylate (III).Alkylation of the phenolic hydroxyl groups of (III) with iodoethane under Williamsom's ether synthesis conditions furnishes the diethoxy napthalenedicarboxylate (IV).Then,alkaline hydrolysis of diester (IV) affords diacid (V),which is further converted to the cyclic anhydride (VI) upon treatment with SOCl2.Condensation of anhydride (VI) with ethyl p-aminophenylacetate (VII) in boiling AcOH leads to the cyclic imide (VIII).Partial reduction of (VIII) with Zn/AcOH produces lactam (IX).The ethyl ester group of (IX) is then selectively hydrolyzed under alkaline conditions to furnish acid (X).Finally,CDI-mediated coupling of acid (X) with benzesulfonamide yields the target N-acyl sulfonamide.
📌 参考资料/链接：
参考文献标题:Benzo(f)isoindol derivs.and their use as EP4 receptor ligands
文献作者:Frye,S.V.; Giblin,G.M.P.; Roomans,S.(GlaxoSmithKline plc)
参考来源:WO 0250033
📄 详细内容
合成路线:Claisen condensation between diethyl phthalate (I) and diethyl succinate (II) in the presence of NaOEt gives rise to the naphthalenedicarboxylate (III).Alkylation of the phenolic hydroxyl groups of (III) with iodoethane under Williamsom's ether synthesis conditions furnishes the diethoxy napthalenedicarboxylate (IV).Then,alkaline hydrolysis of diester (IV) affords diacid (V),which is further converted to the cyclic anhydride (VI) upon treatment with SOCl2.Condensation of anhydride (VI) with ethyl p-aminophenylacetate (VII) in boiling AcOH leads to the cyclic imide (VIII).Partial reduction of (VIII) with Zn/AcOH produces lactam (IX).The ethyl ester group of (IX) is then selectively hydrolyzed under alkaline conditions to furnish acid (X).Finally,CDI-mediated coupling of acid (X) with benzesulfonamide yields the target N-acyl sulfonamide.
参考文献标题:Novel nonprostanoid prostaglandin EP4 receptor antagonist
文献作者:Giblin,G.M.P.; Foord,S.; Wilson,R.; et al.
参考来源:224th ACS Natl Meet (Aug 18 2002,Boston) 2002,Abst MEDI 306
产品链接: CAS No. 439288-66-1››