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【结 构 式】 
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【药物名称】LG-100324 【化学名称】(Z)-4-[(Hydroxyimino)(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]benzoic acid 【CA登记号】221343-42-6 【 分 子 式 】C23H27NO3 【 分 子 量 】365.47654 |
【开发单位】Ligand (Originator) 【药理作用】Antidiabetic Drugs, Antiobesity Drugs, ENDOCRINE DRUGS, METABOLIC DRUGS, Treatment of Nutritional Disorders, Type 2 Diabetes Mellitus, Agents for, ABCA1 Expression Enhancers, Retinoid RXR Agonists |
合成路线1
Friedel-Crafts condensation of 2,5-dichloro-2,5-dimethylhexane (I) with toluene (II) in the presence of AlCl3 or FeCl3 afforded the tetrahydronaphthalene (III). Subsequent acylation of (III) with monomethyl terephthalic acid chloride (IV) provided keto ester (V), which was hydrolyzed to keto acid (VI) with methanolic KOH. Condensation of (VI) with hydroxylamine hydrochloride gave the corresponding oxime as a mixture of geometric isomers. The required Z isomer was then isolated by recrystallization from chloroform/hexane.
| 【1】 Faul, M.M.; Ratz, A.M.; Sullivan, K.A.; Trankle, W.G.; Winneroski, L.L.; Synthesis of novel retinoid X receptor-selective retinoids. J Org Chem 2001, 66, 17, 5772. |
| 【2】 Boehm, M.F.; Canan Koch, S.S.; Cesario, R.M.; Dardashti, L.J.; Nadzan, A.M.; Croston, G.E.; Heyman, R.A.; Synthesis of retinoid X receptor-specific ligands that are potent inducers of adipogenesis in 3T3-L1 cells. J Med Chem 1999, 42, 4, 742. |
| 【3】 Zhang, L.; Boehm, M.F.; Badea, B.A.; White, S.K.; Mais, D.E.; Berger, E.; Suto, C.M.; Goldman, M.E..; Heyman, R.A.; Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. J Med Chem 1994, 37, 18, 2930. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 32201 | Hydroxylamine | 7803-49-8 | H3NO | 详情 | 详情 | |
| (I) | 35216 | 2,5-dichloro-2,5-dimethylhexane | C8H16Cl2 | 详情 | 详情 | |
| (II) | 12890 | Toluene | 108-88-3 | C7H8 | 详情 | 详情 |
| (III) | 35217 | 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene | C15H22 | 详情 | 详情 | |
| (IV) | 25029 | p-Phthalic acid monomethyl ester chloride; Terephthalic acid monomethyl ester chloride; Methyl 4-chlorocarbonylbenzoate | 7377-26-6 | C9H7ClO3 | 详情 | 详情 |
| (V) | 35218 | methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoate | C24H28O3 | 详情 | 详情 | |
| (VI) | 35219 | 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoic acid | C23H26O3 | 详情 | 详情 |