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【结 构 式】 
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【药物名称】SNAP-5540 【化学名称】(-)-1-[3-[2,6-Dimethyl-5-(methycarbamoyl)-4-(4-nitrophenyl)-1,4-dihydropyridin-3-ylcarboxamido]propyl]-4-phenylpiperidine-4-carboxylic acid methyl ester 【CA登记号】166808-20-4 (undefined isomer) 【 分 子 式 】C32H39N5O6 【 分 子 量 】589.69753 |
【开发单位】Synaptic (Originator) 【药理作用】Benign Prostatic Hyperplasia Therapy, RENAL-UROLOGIC DRUGS, alpha1A-Adrenoceptor Antagonists |
合成路线1
Condensation of 4-nitrobenzaldehyde (I) with N-methyl acetoacetamide (II) in the presence of piperidine acetate gave benzylideneacetoacetamide (III). This was further condensed with 2-cyanoethyl 3-amino-2-butenoate (IV) to provide dihydropyridine (V), which was resolved into the enantiomers using chiral HPLC. Then, basic hydrolysis of the cyanoethyl ester from the appropriate enantiomer of (V) yielded carboxylic acid (VI). The aminopropyl piperidine (X) was obtained by esterification of 4-phenyl-4-piperidinecarboxylic acid (VII) with MeOH and H2SO4, followed by alkylation of piperidine (VIII) with 3-bromopropylamine (IX). Finally, amine (X) was coupled to acid (VI) by means of EDC and DMAP to furnish the target compound.
| 【1】 Nagarathnam, D.; Wetzel, J.M.; Miao, S.W.; Marzabadi, M.R.; Chiu, G.; Wong, W.C.; Hong, X.; Fang, J.; Forray, C.; Branchek, T.A.; Heydorn, W.E.; Chang, R.S.; Broten, T.; Schorn, T.W.; Gluchowski, C.; Design and synthesis of novel alpha1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia. J Med Chem 1998, 41, 26, 5320. |
| 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) | 18184 | 4-Nitrobenzaldehyde | 555-16-8 | C7H5NO3 | 详情 | 详情 |
| (II) | 25443 | N-methyl-3-oxobutanamide | 20306-75-6 | C5H9NO2 | 详情 | 详情 |
| (III) | 25444 | (Z)-2-acetyl-N-methyl-3-(4-nitrophenyl)-2-propenamide | C12H12N2O4 | 详情 | 详情 | |
| (IV) | 13987 | 2-cyanoethyl (E)-3-amino-2-butenoate | C7H10N2O2 | 详情 | 详情 | |
| (V) | 25445 | 2-cyanoethyl 2,6-dimethyl-5-[(methylamino)carbonyl]-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate | C19H20N4O5 | 详情 | 详情 | |
| (VI) | 25446 | 2,6-dimethyl-5-[(methylamino)carbonyl]-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid | C16H17N3O5 | 详情 | 详情 | |
| (VII) | 25447 | 4-phenyl-4-piperidinecarboxylic acid | 3627-45-0 | C12H15NO2 | 详情 | 详情 |
| (VIII) | 25448 | methyl 4-phenyl-4-piperidinecarboxylate | C13H17NO2 | 详情 | 详情 | |
| (IX) | 25449 | 3-bromo-1-propanamine; 3-bromopropylamine | 18370-81-5 | C3H8BrN | 详情 | 详情 |
| (X) | 25450 | methyl 1-(3-aminopropyl)-4-phenyl-4-piperidinecarboxylate | C16H24N2O2 | 详情 | 详情 |