Darbufelone mesilate, PD-136095-0073, CI-1004
甲磺酸达布非龙 (5Z)-2-氨基-5-[(4-羟基-3,5-二叔丁基苯基)亚甲基]-1,3-噻唑-4-酮 (5z)-5-[4-羟基-3,5-双(2-甲基-2-丙烯基)苄苯]-2-伊明 O-1,3-噻唑烷-4-1Chemical Name: (Z)-2-Amino-5-(3,5-di-tert-butyl-4-hydroxybenzylidene)thiazol-4(5H)-one methanesulfonate
CAS No. 139340-56-0, 139226-28-1 (free base), 139226-30-5 (free base, undefined isomer), 139226-29-2 (monoHCl)
项目整合开发状态: Phase II/III
项目研究机构: Pfizer (Originator)
合成路线:The condensation of 3,5-bis(tert-butyl)-4-hydroxybenzaldehyde (I) with 2-iminothiazolidin-4-one (II) in refluxing acetic acid gives darbufelone (III),which is then treated with methanesulfonic acid in THF.
合成路线:Knoevenagel condensation of benzaldehyde (I) with rhodanine (II) by means of sodium acetate in acetic acid afforded benzylidenethione (III).Alkylation with iodomethane in the presence of triethylamine gave methylthioether (IV),which was finally condensed with methoxamine hydrochloride and potassium tert--butoxide in refluxing ethanol to yield the title compound.
📌 参考资料/链接：
参考文献标题:3,5-Di-tertiary-butyl-4-hydroxyphenyl-methylene derivs.of 2-substd.thiazolidinones,oxazolidinones,and imidazolidinones as antiinflammatory agents
文献作者:Cetenko,W.A.; Connor,D.T.; Sircar,J.C.; Sorenson,R.J.; Unangst,P.C.(Pfizer Inc.)
参考来源:EP 0449216; JP 1992221371; US 5143928
📄 详细内容
合成路线:The condensation of 3,5-bis(tert-butyl)-4-hydroxybenzaldehyde (I) with 2-iminothiazolidin-4-one (II) in refluxing acetic acid gives darbufelone (III),which is then treated with methanesulfonic acid in THF.
合成路线:Knoevenagel condensation of benzaldehyde (I) with rhodanine (II) by means of sodium acetate in acetic acid afforded benzylidenethione (III).Alkylation with iodomethane in the presence of triethylamine gave methylthioether (IV),which was finally condensed with methoxamine hydrochloride and potassium tert--butoxide in refluxing ethanol to yield the title compound.
参考文献标题:Synthesis and biological evaluation of 5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]oxazoles,-thiazoles,and -imidazoles: Novel dual 5-lipoxygenase and cyclooxygenase inhibitors with antiinflammatory activity
文献作者:Unangst,P.C.; Connor,D.T.; Cetenko,W.A.; Sorenson,R.J.; Kostlan,C.R.; Sircar,J.C.; Wright,C.D.; Schrier,D.J.; Dyer,R.D.
参考来源:J Med Chem 1994,37(2),322
合成路线:The condensation of 3,5-bis(tert-butyl)-4-hydroxybenzaldehyde (I) with 2-iminothiazolidin-4-one (II) in refluxing acetic acid gives darbufelone (III),which is then treated with methanesulfonic acid in THF.
参考文献标题:Oxazole,thiazole,and imidazole derivatives of 2,6-di-tert-butylphenol as dual 5-lipoxygenase and cyclooxygenase inhibitors
文献作者:Schrier,D.J.; Sircar,J.C.; Connor,D.T.; Dyer,R.D.; Cetenko,W.A.; Wright,C.D.; Sorenson,R.J.; Unangst,P.C.
参考来源:Bioorg Med Chem Lett 1993,3(8),1729
合成路线:The condensation of 3,5-bis(tert-butyl)-4-hydroxybenzaldehyde (I) with 2-iminothiazolidin-4-one (II) in refluxing acetic acid gives darbufelone (III),which is then treated with methanesulfonic acid in THF.
参考文献标题:Combination phase II study of irinotecan (CPT 11) and raltitrexed (Tomudex) in advanced colorectal cancer
文献作者:Nobile,M.T.; et al.
参考来源:Proc Amer Soc Clin Oncol 1999,1818