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【结 构 式】 
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【药物名称】MOL-294 【化学名称】cis-4-Hydroxy-4-(8-methyl-1,3-dioxo-2-phenyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl)-2-butynoic acid methyl ester 【CA登记号】203455-50-9 (undefined isomer) 【 分 子 式 】C18H17N3O5 【 分 子 量 】355.35329 |
【开发单位】Molecumetics (Originator) 【药理作用】Asthma Therapy, RESPIRATORY DRUGS, NF-kappaB (NFKB) Activation Inhibitors |
合成路线1
Addition of methyl propiolate (I) to 2,4-hexadienal (II) using lithium hexamethyldisilazide afforded diene (III). Subsequent cycloaddition of (III) to 4-phenyl urazole (IV) in the presence of iodobenzene diacetate produced the corresponding triazolopyridazine as a diastereomeric mixture, from which the required cis isomer was isolated by flash chromatography.
| 【1】 McMillan, M.; Cudaback, E.; Misra-Press, A.; et al.; Synthesis and biological studies of a novel inhibitor of NF-kappaB. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 213. |
| 【2】 Eguchi, M.; Qabar, M.N.; Ferguson, M.D.; Babu, S.; Boatman, P.D. Jr.; McMillan, M.K.; Kahn, M.; Ogbu, C.O.; Lum, C.T.; Meara, J.P.; Kim, H.-O.; Urban, J. (Molecumetics Ltd.); Use of beta-sheet mimetics as protease and kinase inhibitors and as inhibitors of transcription factors. US 6117896; WO 9805333 . |
| 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) | 19588 | methyl propiolate | 922-67-8 | C4H4O2 | 详情 | 详情 |
| (II) | 29433 | (2E,4E)-2,4-hexadienal | 142-83-6 | C6H8O | 详情 | 详情 |
| (III) | 29434 | methyl (5E,7E)-4-hydroxy-5,7-nonadien-2-ynoate | C10H12O3 | 详情 | 详情 | |
| (IV) | 11749 | 4-Phenyl-3H-1,2,4-triazole-3,5(4H)-dione; 4-Phenyl-1,2,4-triazoline-3,5-dione | 4233-33-4 | C8H5N3O2 | 详情 | 详情 |
Extended Information