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【结 构 式】 
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【药物名称】 【化学名称】2(R)-[2,6-Dibromo-4-(6-bromobenzo[b]naphtho[2,3-d]furan-11-yl)phenoxy]-3-phenylpropionic acid 【CA登记号】 【 分 子 式 】C31H19Br3O4 【 分 子 量 】695.20668 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, Protein Tyrosine Phosphatase PTP-1B Inhibitors |
合成路线1
Condensation of salicylaldehyde (I) with 2-bromoacetophenone (II) produced benzofuranyl phenyl ketone (III), which was reduced to 2-benzyl benzofuran (IV) under Wolff-Kishner conditions. Subsequent Friedel-Crafts acylation of (IV) with anisoyl chloride (V) employing SnCl4 afforded ketone (VI). Methyl ether cleavage in (VI) with concomitant intramolecular cyclization, followed by dehydration by means of BBr3 gave rise to benzo naphthofuran (VII). This was brominated in AcOH to yield tribromo derivative (VIII). Mitsunobu coupling of (VIII) with (S)-methyl-2-hydroxy-3-phenylpropionate (IX) furnished ether (X). Finally, the methyl ester group of (X) was hydrolyzed with KOH.
| 【1】 Dietrich, A.; Katz, A.; Sullivan, D.; Wrobel, J.; Sawicki, D.R.; Tio, C.; Li, Z.; Seestaller, L.; Wu, L.; Zhang, Z.-Y.; Sredy, J.; Moxham, C.; PTP1B inhibition and antihyperglycemic activity in the ob/ob mouse model of novel 11-arylbenzo[b]naphto[2,3-d]furans and 11-arylbenzo[b]naphtho[2,3-d]thiophenes. J Med Chem 1999, 42, 17, 3199-3202. |
| 【2】 Dietrich, A.J.; Wrobel, J.E.; Li, Z. (American Home Products Corp.); 11-Aryl-benzo[b]naphtho[2,3-d]furans and 11-aryl-benzo[b]naphtho[2,3-d]thiophenes useful in the treatment of insulin resistance and hyperglycemia. WO 9958521 . |
| 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) | 21351 | 2-Hydroxybenzaldehyde;Salicylic aldehyde；2-Formylphenol;salicylaldehyde | 90-02-8 | C7H6O2 | 详情 | 详情 |
| (II) | 10315 | 2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone | 70-11-1 | C8H7BrO | 详情 | 详情 |
| (III) | 33663 | 1-benzofuran-2-yl(phenyl)methanone | C15H10O2 | 详情 | 详情 | |
| (IV) | 33664 | 2-benzyl-1-benzofuran | C15H12O | 详情 | 详情 | |
| (V) | 22671 | 4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride | 100-07-2 | C8H7ClO2 | 详情 | 详情 |
| (VI) | 33665 | (2-benzyl-1-benzofuran-3-yl)(4-methoxyphenyl)methanone | C23H18O3 | 详情 | 详情 | |
| (VII) | 33666 | 4-naphtho[2,3-b][1]benzofuran-11-ylphenol | C22H14O2 | 详情 | 详情 | |
| (VIII) | 33667 | 2,6-dibromo-4-(6-bromonaphtho[2,3-b][1]benzofuran-11-yl)phenol | C22H11Br3O2 | 详情 | 详情 | |
| (IX) | 13878 | methyl (2R)-2-hydroxy-3-phenylpropanoate | C10H12O3 | 详情 | 详情 | |
| (X) | 33668 | methyl (2R)-2-[2,6-dibromo-4-(6-bromonaphtho[2,3-b][1]benzofuran-11-yl)phenoxy]-3-phenylpropanoate | C32H21Br3O4 | 详情 | 详情 |