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【结 构 式】 
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【药物名称】Atiprimod hydrochloride, SK&F-106615-I2(dimaleate), SK&F-106615-A2 【化学名称】2-[3-(Diethylamino)propyl]-8,8-dipropyl-2-azaspiro[4.5]decane dihydrochloride 【CA登记号】130065-61-1, 183063-72-1 (dimaleate), 123018-47-3 (free base) 【 分 子 式 】C22H46Cl2N2 【 分 子 量 】409.53132 |
【开发单位】Callisto Pharmaceuticals (Orphan Drug), AnorMED (Originator), GlaxoSmithKline (Originator), Callisto Pharmaceuticals (Licensee) 【药理作用】Antiarthritic Drugs, Bone Diseases, Treatment of, Bone Resorption Inhibitors, Colorectal Cancer Therapy, GASTROINTESTINAL DRUGS, Inflammatory Bowel Disease, Agents for, METABOLIC DRUGS, Multiple Myeloma Therapy, Oncolytic Drugs, Rheumatoid Arthritis, Treatment of, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Treatment of Osteoporosis |
合成路线1
Piperidine-catalyzed condensation of ethyl cyanoacetate with (I) (1) afforded cyanoester (II). Michael addition of KCN to (II) gave dinitrile (III), which was hydrolyzed under basic conditions to afford diacid (IV). Condensation of (IV) with N,N-diethylaminopropylamine afforded the desired imide (V). Reduction of (V) with lithium aluminum hydride gave the required diamine which was treated with aqueous HCl/n-propanol to yield the diamine as the dihydrochloride salt, SK&F 106615-A2 (VI).
| 【1】 Wright, C.S.; Bagder, A.; SK&F-106615. Drugs Fut 1995, 20, 9, 893. |
| 【2】 Badger, A.M.; Dimartino, M.J.; Mirabelli, C.K.; Cheeseman, E.N.; Dorman, J.W.; Picker, D.H.; Schwartz, D.A. (SmithKline Beecham plc); Immunomodulatory azaspiranes. AU 8825333; EP 0310321; JP 1991500290; US 4963557; WO 8902889 . |
| 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) | 13411 | 4,4-Dipropylcyclohexanone | 123018-62-2 | C12H22O | 详情 | 详情 |
| (II) | 13412 | ethyl 2-cyano-2-(4,4-dipropylcyclohexylidene)acetate | C17H27NO2 | 详情 | 详情 | |
| (III) | 16471 | 1-(cyanomethyl)-4,4-dipropylcyclohexanecarbonitrile | C15H24N2 | 详情 | 详情 | |
| (IV) | 13413 | 1-(Carboxymethyl)-4,4-dipropylcyclohexanecarboxylic acid | C15H26O4 | 详情 | 详情 | |
| (V) | 16473 | 2-[3-(diethylamino)propyl]-8,8-dipropyl-2-azaspiro[4.5]decane-1,3-dione | C22H40N2O2 | 详情 | 详情 |