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【结 构 式】

【药物名称】VML-530, ABT-080

【化学名称】4,4-Bis[4-(quinolin-2-ylmethoxy)phenyl]pentanoic acid sodium salt

【CA登记号】

【 分 子 式 】C37H31N2NaO4

【 分 子 量 】590.66042

【开发单位】Abbott (Originator), Vernalis (Licensee)

【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Leukotriene Synthesis Inhibitors

合成路线1

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.

1 Brooks, C.D.W.; Bhatia, P.; Kolasa, T.; Stewart, A.O.; Gunn, D.E.; Craig, R.A. (Abbott Laboratories Inc.); Symmetrical bis-heteroarylmethoxyphenylalkyl carboxylates as inhibitors of leukotriene biosynthesis. EP 0862557; US 5795900; WO 9712867 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 22391 4,4-bis(4-hydroxyphenyl)pentanoic acid 126-00-1 C17H18O4 详情 详情
(II) 22392 methyl 4,4-bis(4-hydroxyphenyl)pentanoate C18H20O4 详情 详情
(III) 13162 2-(Chloromethyl)quinoline; alpha-Chloroquinaldine 4377-41-7 C10H8ClN 详情 详情
(IV) 22394 methyl 4,4-bis[4-(2-quinolinylmethoxy)phenyl]pentanoate C38H34N2O4 详情 详情
(V) 22395 4,4-bis[4-(2-quinolinylmethoxy)phenyl]pentanoic acid C37H32N2O4 详情 详情

合成路线2

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.

1 Gunn, D.E.; Bhatia, P.; Kolasa, T.; et al.; Symmetrical bis(heteroarylmethoxyphenyl)alkylcarboxylic acids as inhibitors of leukotriene biosynthesis. J Med Chem 2000, 43, 17, 3322.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 23540 Phenol 108-95-2 C6H6O 详情 详情
(II) 36170 4-oxopentanoic acid 123-76-2 C5H8O3 详情 详情
(III) 22391 4,4-bis(4-hydroxyphenyl)pentanoic acid 126-00-1 C17H18O4 详情 详情
(IV) 22392 methyl 4,4-bis(4-hydroxyphenyl)pentanoate C18H20O4 详情 详情
(V) 13162 2-(Chloromethyl)quinoline; alpha-Chloroquinaldine 4377-41-7 C10H8ClN 详情 详情
(VI) 22394 methyl 4,4-bis[4-(2-quinolinylmethoxy)phenyl]pentanoate C38H34N2O4 详情 详情
(VII) 50960 Methyl levulinate C6H10O3 详情 详情
Extended Information