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【结 构 式】 
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【药物名称】 【化学名称】4-[N-(2,2,4,4-Tetramethyl-3,4-dihydro-2H-1-benzothiopyran-6-yl)carbamoyl]benzoic acid methyl ester 【CA登记号】203855-93-0 【 分 子 式 】C22H25NO3S 【 分 子 量 】383.51345 |
【开发单位】Oklahoma State University (Originator), University of Oklahoma Health Sci. Cent. (Originator) 【药理作用】ONCOLYTIC DRUGS, ABCA1 Expression Enhancers, Retinoid RAR Agonists, Retinoid RXR Agonists |
合成路线1
Thiophenol (I) is treated with mesityl oxide (II) in CHCl3 and Et3N to yield derivative (III), which is then converted into alcohol (IV) by means of methylmagnesium iodide in Et2O. Cyclization of (IV) by means of AlCl3 in CS2 affords benzothiopyrane derivative (V) (1), which is nitrated by means of HNO3 and Ac2O or HOAc followed by treatment with Na2CO3 to provide (VI). Nitro derivative (VI) is then reduced with TiCl3 and HOAc or HCl and treated with NaOH to yield (VII). Amine (VII) is finally acylated with acid chloride (VIII) in benzene and pyridine.
| 【1】 Spruce, L.W.; et al.; Novel heteroarotinoids: Synthesis and biological activity. J Med Chem 1991, 34, 1, 430. |
| 【2】 Lu, S.; Zacheis, D.; Dhar, A.; et al.; Heteroarotinoids inhibit head and neck cancer cell lines in vitro and in vivo through both RAR and RXR retinoic acid receptors. J Med Chem 1999, 42, 21, 4434. |
| 【3】 Nelson, E.C.; Madler, M.M.; Subramanian, S.; Birckbichler, P.J.; Berlin, K.D.; Patterson, M.K. Jr.; Benbrook, D.M. (Oklahoma State University); Heteroarotinoids - Anticancer agents with receptor specificity and TGASE activity. WO 9807716 . |
| 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) | 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 |
| (II) | 42266 | 4-methyl-3-penten-2-one | 141-79-7 | C6H10O | 详情 | 详情 |
| (III) | 42267 | 4-methyl-4-(phenylsulfanyl)-2-pentanone | C12H16OS | 详情 | 详情 | |
| (IV) | 42268 | 2,4-dimethyl-4-(phenylsulfanyl)-2-pentanol | C13H20OS | 详情 | 详情 | |
| (V) | 42269 | 2,2,4,4-tetramethylthiochromane | C13H18S | 详情 | 详情 | |
| (VI) | 42270 | 2,2,4,4-tetramethyl-6-nitrothiochromane | C13H17NO2S | 详情 | 详情 | |
| (VII) | 42271 | 2,2,4,4-tetramethyl-6-thiochromanamine; 2,2,4,4-tetramethyl-3,4-dihydro-2H-thiochromen-6-ylamine | C13H19NS | 详情 | 详情 | |
| (VIII) | 42272 | 4-acetylbenzoyl chloride | C9H7ClO2 | 详情 | 详情 |