SB-235375
Chemical Name: 2-[2-Phenyl-4-[N-[1(S)-phenylpropyl]carbamoyl]quinolin-3-yloxy]acetic acid
CAS No. 224961-34-6, 192704-51-1 (monoHCl), 224633-16-3 (monosodium salt)
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The quinolinecarboxylic acid (III) was obtained by the Pfitzinger reaction of isatin (I) with 2-methoxyacetophenone (II) in ethanolic KOH at 80 C.Subsequent methyl ether cleavage in (III) using concentrated HI provided 3-hydroxy-2-phenylquinoline-4-carboxylic acid (IV).Coupling of acid (IV) with (S)-1-phenylpropylamine (V) by means of DCC and HOBt gave amide (VI).Ester (VIII) was then obtained by alkylation of the 3-hydroxy quinoline (VI) with ethyl bromoacetate (VII) in the presence of K2CO3 and KI.Finally,hydrolysis of the ethyl ester (VIII) with refluxing HCl afforded the corresponding carboxylic acid.
📌 参考资料/链接：
参考文献标题:Quinoline derivs.
文献作者:Giardina,G.A.M.; Grugni,M.; Raveglia,L.F.; Farino,C.(GlaxoSmithKline plc)
参考来源:EP 0876347; JP 2000501104; US 6277862; WO 9721680
📄 详细内容
合成路线:Condensation of isatin (I) with 2-methoxyacetophenone (II) in the presence of KOH afforded quinolinecarboxylic acid (III).Subsequent demethylation of the ether function of (III) with refluxing 57% HI gave (IV),which was then condensed with (S)-1-phenylpropyl amine (V) using DCC and HOBt to yield the title amide.
合成路线:The quinolinecarboxylic acid (III) was obtained by the Pfitzinger reaction of isatin (I) with 2-methoxyacetophenone (II) in ethanolic KOH at 80 C.Subsequent methyl ether cleavage in (III) using concentrated HI provided 3-hydroxy-2-phenylquinoline-4-carboxylic acid (IV).Coupling of acid (IV) with (S)-1-phenylpropylamine (V) by means of DCC and HOBt gave amide (VI).Ester (VIII) was then obtained by alkylation of the 3-hydroxy quinoline (VI) with ethyl bromoacetate (VII) in the presence of K2CO3 and KI.Finally,hydrolysis of the ethyl ester (VIII) with refluxing HCl afforded the corresponding carboxylic acid.
参考文献标题:Discovery of a novel class of selective non-peptid
文献作者:Giardina,G.A.; Raveglia,L.F.; Grugni,M.; Sarau,H.M.; Farina,C.; Medhurst,A.D.; Graziani,D.; Schmidt,D.B.; Rigolio,R.; Luttmann,M.; Cavagnera,S.; Foley,J.J.; Vecchietti,V.; Hay,D.W.
参考来源:J Med Chem 1999,42(6),1053
产品链接: CAS No. 224961-34-6››