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【结 构 式】 
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【药物名称】WAY-151693 【化学名称】2-[N-(4-Methoxyphenylsulfonyl)-N-(3-pyridinylmethyl)amino]-3-methylbenzohydroxamic acid hydrochloride 【CA登记号】206551-25-9, 206547-44-6 (free base) 【 分 子 式 】C21H22ClN3O5S 【 分 子 量 】463.94359 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Antiarthritic Drugs, ONCOLYTIC DRUGS, Osteoarthritis, Treatment of, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Angiogenesis Inhibitors, MMP-13 (Collagenase 3) Inhibitors, MMP-9 (Gelatinase B) Inhibitors |
合成路线1
Sulfonylation of methyl 3-methylanthranilate (I) with 4-methoxybenzenesulfonyl chloride (II) provided the sulfonamide (III). This was then N-alkylated with 3-picolyl chloride hydrochloride (IV) in the presence of K2CO3 to afford (V). Ester (V) hydrolysis with LiOH or NaOH provided carboxylic acid (VI), which was further activated as the corresponding acid chloride (VII) using oxalyl chloride in the presence of DMF. Coupling of acid chloride (VII) with hydroxylamine hydrochloride furnished the target hydroxamic acid, which was finally treated with HCl to produce the title hydrochloride salt.
| 【1】 Levin, J.I.; DiJoseph, J.F.; Du, M.T.; et al.; The discovery of anthranilic acid-based MMP inhibitors. Part 1. SAR of the 3-position. Bioorg Med Chem Lett 2001, 11, 2, 235. |
| 【2】 Gu, Y.; Nelson, F.C.; Zask, A.; Du, M.T.; Levin, J.I.; Venkatesan, M. (American Cyanamid Co.); Preparation and use of orthosulfonamido aryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors. US 5929097 . |
| 【3】 Nelson, F.C.; Venkatesan, A.M.; Levin, J.I.; Du, M.T.; Gu, Y.; Zask, A. (American Cyanamid Co.); The preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors. WO 9816503 . |
| 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) | 48424 | methyl 2-amino-3-methylbenzoate | C9H11NO2 | 详情 | 详情 | |
| (II) | 15719 | 4-methoxybenzenesulfonyl chloride | 98-68-0 | C7H7ClO3S | 详情 | 详情 |
| (III) | 48425 | methyl 2-[[(4-methoxyphenyl)sulfonyl]amino]-3-methylbenzoate | C16H17NO5S | 详情 | 详情 | |
| (IV) | 15793 | 3-(Chloromethyl)pyridine | 3099-31-8 | C6H6ClN | 详情 | 详情 |
| (V) | 48426 | methyl 2-[[(4-methoxyphenyl)sulfonyl](3-pyridinylmethyl)amino]-3-methylbenzoate | C22H22N2O5S | 详情 | 详情 | |
| (VI) | 48427 | 2-[[(4-methoxyphenyl)sulfonyl](3-pyridinylmethyl)amino]-3-methylbenzoic acid | C21H20N2O5S | 详情 | 详情 | |
| (VII) | 48428 | 2-[[(4-methoxyphenyl)sulfonyl](3-pyridinylmethyl)amino]-3-methylbenzoyl chloride | C21H19ClN2O4S | 详情 | 详情 |