【结 构 式】 |
【药物名称】A-292949 【化学名称】1-Acetyl-4-[3-[3-chloro-4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)phenyl]-2(E)-propenoyl]piperazine 【CA登记号】280750-31-4 【 分 子 式 】C23H23ClN2O4S 【 分 子 量 】458.96776 |
【开发单位】Abbott (Originator) 【药理作用】IMMUNOMODULATING AGENTS, Immunosuppressants, LFA-1/ICAM-1 Interaction Inhibitors |
合成路线1
Aromatic nucleophilic substitution of 3-chloro-4-fluorobenzaldehyde (I) with methyl 3-mercaptopropionate (II) yielded the mercapto aldehyde (III). This was subjected to Knoevenagel condensation with malonic acid to furnish the cinnamic acid derivative (IV), which was further converted to the corresponding acid chloride (V) by using oxalyl chloride. Condensation of acid chloride (V) with N-acetylpiperazine (VI) yielded the diacyl piperazine (VII). The protected benzenethiol of (VII) was released by treatment of the beta-mercaptopropionate (VII) with potassium tert-butoxide to give the potassium thiolate (VIII). Finally, Ullmann coupling of (VIII) with 6-iodobenzodioxan (IX) furnished the title compound.
【1】 Liu, G.; Okasinski, O.F.; DeVries, P.; Mendoza, R.; Leitza, S.; Olejniczak, E.T.; von Geldern, T.W.; Huth, J.R.; Fesik, S.W.; Reilly, E.B.; Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties. J Med Chem 2001, 44, 8, 1202. |
【2】 Jae, H.-S.; Pei, Z.; Staeger, M.A.; Gunawardana, I.W.; Winn, M.; Freeman, J.C.; Liu, G.; Link, J.; Boyd, S.A.; Zhu, G.-D.; Von Geldern, T.W.; Xin, Z.; Lynch, J.K.; Wang, S. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. WO 0059880 . |
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) | 49749 | 3-Chloro-4-fluorobenzaldehyde; 4-Fluoro-3-chlorobenzaldehyde | 34328-61-5 | C7H4ClFO | 详情 | 详情 |
(II) | 11418 | methyl 3-sulfanylpropanoate; Methyl 3-mercaptopropionate | 2935-90-2 | C4H8O2S | 详情 | 详情 |
(III) | 48173 | methyl 3-[(2-chloro-4-formylphenyl)sulfanyl]propanoate | C11H11ClO3S | 详情 | 详情 | |
(IV) | 48174 | (E)-3-[3-chloro-4-[(3-methoxy-3-oxopropyl)sulfanyl]phenyl]-2-propenoic acid | C13H13ClO4S | 详情 | 详情 | |
(V) | 48175 | methyl 3-([2-chloro-4-[(E)-3-chloro-3-oxo-1-propenyl]phenyl]sulfanyl)propanoate | C13H12Cl2O3S | 详情 | 详情 | |
(VI) | 20674 | N-Acetyl piperazine; 1-(1-piperazinyl)-1-ethanone | 13889-98-0 | C6H12N2O | 详情 | 详情 |
(VII) | 48176 | methyl 3-([4-[(E)-3-(4-acetyl-1-piperazinyl)-3-oxo-1-propenyl]-2-chlorophenyl]sulfanyl)propanoate | C19H23ClN2O4S | 详情 | 详情 | |
(VIII) | 48177 | potassium 4-[(E)-3-(4-acetyl-1-piperazinyl)-3-oxo-1-propenyl]-2-chlorobenzenethiolate | C15H16ClKN2O2S | 详情 | 详情 | |
(IX) | 49750 | 3,4-Ethylenedioxyiodobenzene | 57744-67-9 | C8H7IO2 | 详情 | 详情 |