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【结 构 式】 
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【药物名称】SNAP-5150 【化学名称】2,6-Dimethyl-N3-[3-(4,4-diphenylpiperidin-1-yl)propyl]-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxamide 【CA登记号】166806-40-2, 166808-84-0 ((-)-enantiomer), 166808-83-9 ((+)-enantiomer) 【 分 子 式 】C35H39N5O4 【 分 子 量 】593.73218 |
【开发单位】Synaptic (Originator) 【药理作用】Benign Prostatic Hyperplasia Therapy, RENAL-UROLOGIC DRUGS, alpha1-Adrenoceptor Antagonists |
合成路线1
Treatment of a benzenic solution of 4-piperidone hydrate (I) with anhydrous AlCl3 provided 4,4-diphenylpiperidine (II). Then, conjugate addition of acrylonitrile (III) in the presence of triethylamine in ethanol gave the cyanoethylpiperidine (IV), which was reduced with borane in THF to afford the intermediate primary amine (V). Dihydropyridine (IX) was prepared by Hantzsch synthesis by condensation of 3-aminocrotonamide (VI), 4-nitrobenzaldehyde (VII) and cyanoethyl acetoacetate (VIII) in refluxing ethanol. Cyanoethyl ester was then cleaved with dilute KOH at 0 C to give acid (X), which was finally coupled with amine (V) by treatment with DEC to yield the target amide.
| 【1】 Cox, E.D.; et al.; Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate. J Med Chem 1998, 41, 14, 2643. |
| 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) | 18178 | 4,4-piperidinediol | 73390-11-1 | C5H11NO2 | 详情 | 详情 |
| (II) | 13154 | 4,4-Diphenylpiperidine | C17H19N | 详情 | 详情 | |
| (III) | 10847 | Acrylonitrile | 107-13-1 | C3H3N | 详情 | 详情 |
| (IV) | 18181 | 3-(4,4-diphenyl-1-piperidinyl)propanenitrile | C20H22N2 | 详情 | 详情 | |
| (V) | 18182 | 3-(4,4-diphenyl-1-piperidinyl)-1-propanamine; 3-(4,4-diphenyl-1-piperidinyl)propylamine | C20H26N2 | 详情 | 详情 | |
| (VI) | 18183 | (E)-3-amino-2-butenamide | C4H8N2O | 详情 | 详情 | |
| (VII) | 18184 | 4-Nitrobenzaldehyde | 555-16-8 | C7H5NO3 | 详情 | 详情 |
| (VIII) | 13993 | 2-cyanoethyl 3-oxobutanoate | C7H9NO3 | 详情 | 详情 | |
| (IX) | 18186 | 2-cyanoethyl 5-(aminocarbonyl)-2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate | C18H18N4O5 | 详情 | 详情 | |
| (X) | 18187 | 5-(aminocarbonyl)-2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid | C15H15N3O5 | 详情 | 详情 |