【药物名称】VML-530, ABT-080
化学结构式(Chemical Structure):
参考文献No.33087
标题:Symmetrical bis-heteroarylmethoxyphenylalkyl carboxylates as inhibitors of leukotriene biosynthesis
作者:Brooks, C.D.W.; Bhatia, P.; Kolasa, T.; Stewart, A.O.; Gunn, D.E.; Craig, R.A. (Abbott Laboratories Inc.)
来源:EP 0862557; US 5795900; WO 9712867
合成路线图解说明:

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.

参考文献No.588422
标题:Symmetrical bis(heteroarylmethoxyphenyl)alkylcarboxylic acids as inhibitors of leukotriene biosynthesis
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.
来源:J Med Chem 2000,43(17),3322
合成路线图解说明:

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.

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