【药物名称】
【化学名】
5-Bromo-2-[N-[4-(2-butynyloxy)phenylsulfonyl]-N-methylamino]-3-(4-methylpiperazin-1-ylmethyl)benzohydroxamic acid
【CAS登记号】
【结构式】
【分子式】
C24-H29-Br-N4-O5-S
【分子量】
565.4861
【原研厂家】
Amgen (Originator), Wyeth Pharmaceuticals (Originator)
【作用类别】
Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, TNF-alpha-Converting Enzyme (TACE) Inhibitors
【研发状态】
Preclinical
【合成情况】
〖来源〗
Bioorg Med Chem Lett
〖合成路线〗
〖标题〗
Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 2: SAR of the acetylenic P1' group
〖合成方法〗
Sulfonylation of methyl 5-bromo-3-methylanthranilate (I) with acid chloride (II) affords sulfonamide (III). Subsequent alkylation of the sulfonamide N of (III) with iodomethane and K2CO3 yields (IV). After protection of the phenolic hydroxyl group of (IV) as the silyl ether (V), benzylic halogenation with N-bromosuccinimide furnishes bromide (VI). Displacement of its benzylic bromide with 1-methylpiperazine (VII) occurs with concomitant desilylation to give (VIII). Mitsunobu coupling of phenol (VIII) with 2-butyn-1-ol (IX) leads to the propargyl ether (X). The methyl ester group of (X) is then hydrolyzed under alkaline conditions to furnish the carboxylic acid (XI).
〖作者〗
Levin, J.I.; Chen, J.M.; Du, M.T.; Nelson, F.C.; Killar, L.M.; Skala, S.; Sung, A.; Jin, G.; Cowling, R.; Barone, D.; March, C.J.; Mohler, K.M.; Black, R.A.; Skotnicki, J.S.
〖参考〗
Levin, J.I.; Chen, J.M.; Du, M.T.; Nelson, F.C.; Killar, L.M.; Skala, S.; Sung, A.; Jin, G.; Cowling, R.; Barone, D.; March, C.J.; Mohler, K.M.; Black, R.A.; Skotnicki, J.S.; Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 2: SAR of the acetylees/10_6_fxqfygbxevpnbnwv.html">2籓ࡳ3耀1-6 (Na salt),
〖出处〗
Bioorg Med Chem Lett2002,12,(8):1199
〖备注〗
〖来源〗
Bioorg Med Chem Lett
〖合成路线〗
〖标题〗
Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 2: SAR of the acetylenic P1' group
〖合成方法〗
Acid (XI) is then activated as the corresponding acid chloride (XII) upon treatment with oxalyl chloride in the presence of DMF. Finally, reaction of acid chloride (XII) with hydroxylamine leads to the title hydroxamic acid.
〖作者〗
Levin, J.I.; Chen, J.M.; Du, M.T.; Nelson, F.C.; Killar, L.M.; Skala, S.; Sung, A.; Jin, G.; Cowling, R.; Barone, D.; March, C.J.; Mohler, K.M.; Black, R.A.; Skotnicki, J.S.
〖参考〗
Levin, J.I.; Chen, J.M.; Du, M.T.; Nelson, F.C.; Killar, L.M.; Skala, S.; Sung, A.; Jin, G.; Cowling, R.; Barone, D.; March, C.J.; Mohler, K.M.; Black, R.A.; Skotnicki, J.S.; Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 2: SAR of the acetylees/10_6_fxqfygbxevpnbnwv.html">2籓ࡳ3耀1-6 (Na salt),
〖出处〗
Bioorg Med Chem Lett2002,12,(8):1199
〖备注〗
ChemDrug版权识别码:75475462832427453
