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【结 构 式】

【药物名称】Fluticasone Furoate, 685698,698,GW-685698,GW-685698X, Allermist

【化学名称】6α,9α-Difluoro-17α-(furan-2-ylcarbonyloxy)-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17-carbothioic acid S-(fluoromethyl) ester

【CA登记号】397864-44-7

【 分 子 式 】C27H29F3O6S

【 分 子 量 】538.5768

【开发单位】GlaxoSmithKline (GB, US).

【药理作用】Glucocorticoid receptor agonist, Intranasal corticosteroid

合成路线1

The starting 6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid (I) is converted to the analogous carbothioic acid (II) via activation with carbonyl diimidazole, followed by reaction with hydrogen sulfide gas (1). The α-hydroxyl group of (II) is then selectively acylated with 2-furoyl chloride (III) to give the 17-furoate ester (IV) (2, 3). Finally, condensation of thioacid (IV) with bromofluoromethane under basic conditions provides the target fluoromethyl thioester (2-4).

1 Phillipps, G.H., Bain, B.M., Williamson, C., Steeples, I.P., Laing, S.B. (Glaxo Group, Ltd.). Androstane 17β-carbothioates. GB 2088877.
2 Biggadike, K., Jones, P., Payne, J.J. (Glaxo Group, Ltd.). 17beta-Carbothioate 17alpha-arylcarbonyloxyoxy androstane derivative as anti-inflammatory agents. EP 1305330, JP 2004505990, US 6537983, US 2003045512, WO 0212266.
3 Biggadike, K., Coote, S.J., Noga, B., Van Oort, M.M. (Glaxo Group, Ltd.). Amorphous fluticasone 2-furoate, pharmaceutical compositions thereof and its conversion to the crystalline unsolvated form. EP 1480996, JP 2005522442, US 2005152845, WO 03066655.
4 Partridge, J.J., Walker, D.S. (SmithKline Beecham Corp.). A method for preparing fluticasone derivatives. WO 03013427. 5. Prous Science Disease Briefings: Allergic Rhinitis (online publication). Updated 2007.
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) 14476 (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid C21H26F2O5 详情 详情
(II) 14481 (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carbothioic S-acid C21H26F2O4S 详情 详情
(III) 26093 2-Furoyl chloride 527-69-5 C5H3ClO2 详情 详情
(IV) 65207 (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11-hydroxy-17-furoyloxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carbothioic S-acid   C26H26F2O6S 详情 详情
Extended Information