VML-530, ABT-080
Chemical Name: 4,4-Bis[4-(quinolin-2-ylmethoxy)phenyl]pentanoic acid sodium salt
项目整合开发状态: Phase I
项目研究机构: Abbott (Originator), Vernalis (Licensee)
合成路线:Esterification of 4,4-bis(4-hydroxyphenyl)pentanoic acid (I) was performed in a refluxing methanolic solution,using sulfuric acid as the catalyst.The resulting methyl ester (II) was alkylated on both phenolic groups with 2-(chloromethyl)quinoline hydrochloride (III) in the presence of potassium carbonate to afford IV.Hydrolysis of this ester (IV) with NaOH in a refluxing mixture of dioxane-methanol yielded acid (V),which was then converted into the sodium salt on treatment with one equivalent of NaOH in dioxane-methanol.
📌 参考资料/链接：
参考文献标题:Symmetrical bis-heteroarylmethoxyphenylalkyl carboxylates as inhibitors of leukotriene biosynthesis
文献作者:Brooks,C.D.W.; Bhatia,P.; Kolasa,T.; Stewart,A.O.; Gunn,D.E.; Craig,R.A.(Abbott Laboratories Inc.)
参考来源:EP 0862557; US 5795900; WO 9712867
📄 详细内容
合成路线:The reaction of phenol (I) with 4-oxopentanoic acid (II) by means of H2SO4 gives 4,4-bis(4-hydroxyphenyl)pentanoic acid (III),which is esterified with MeOH and H2SO4 to yield the methyl pentanoate (IV).The condensation of (IV) with 2-(chloromethyl)quinoline (V) by means of K2CO3 in DMF affords the adduct (VI),which is finally hydrolyzed with NaOH in methanol/dioxane to provide the target sodium salt.Alternatively,the intermediate methyl pentanoate (IV) can also be obtained by direct condensation of phenol (I) with methyl 4-oxopentanoate (VII) by means of H2SO4 as before.
参考文献标题:Symmetrical bis(heteroarylmethoxyphenyl)alkylcarboxylic acids as inhibitors of leukotriene biosynthesis
文献作者:Kolasa,T.; Gunn,D.E.; Bhatia,P.; Basha,A.; Craig,R.A.; Stewart,A.O.; Bouska,J.B.; Harris,R.R.; Hulkower,K.I.; Malo,P.E.; Bell,R.L.; Carter,G.W.; Brooks,C.D.
参考来源:J Med Chem 2000,43(17),3322