|
【结 构 式】 
|
【药物名称】SNAP-5399 【化学名称】2-(2-Aminoethoxymethyl)-N3-[3-(4,4-diphenylpiperidin-1-yl)propyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxamide 【CA登记号】166807-77-8, 166810-98-6 ((-)-enantiomer), 166810-99-7 ((+)-enantiomer) 【 分 子 式 】C38H46N6O5 【 分 子 量 】666.82752 |
【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
Hantzsch condensation of the (azidoethoxy)ketoester (I) with the benzylidene ketoester (II) formed the protected dihydropyridine (III). Selective deprotection of the cyanoethyl ester under basic conditions provided carboxylic acid (IV), which was further converted to amide (V). Then, acid cleavage of the tert-butyl ester gave acid (VI). Coupling with the (aminopropyl)piperidine (VII) furnished the corresponding amide (VIII). Finally, the azido group was reduced to the target amine by means of trimethyl phosphine.
| 【1】 Tyring, S.K.; Vander Straten, M.; Carrasco, D.; Tetrahedron Lett 1998, 39, 30, 5293-96. |
| 【2】 Hong, X.; Nagarathnam, D.; Marzbadi, M.R.; et al.; Design and synthesis of novel dihydropyridine alpha-1A antagonists. Bioorg Med Chem Lett 1999, 9, 19, 2843. |
| 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) | 31725 | tert-butyl 4-(2-azidoethoxy)-3-oxobutanoate | C10H17N3O4 | 详情 | 详情 | |
| (II) | 31726 | 2-cyanoethyl (Z)-3-(4-nitrophenyl)-2-propionyl-2-propenoate | C15H14N2O5 | 详情 | 详情 | |
| (III) | 31727 | 3-(tert-butyl) 5-(2-cyanoethyl) 2-[(2-azidoethoxy)methyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate | C25H30N6O7 | 详情 | 详情 | |
| (IV) | 31728 | 6-[(2-azidoethoxy)methyl]-5-(tert-butoxycarbonyl)-2-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid | C22H27N5O7 | 详情 | 详情 | |
| (V) | 31729 | tert-butyl 5-(aminocarbonyl)-2-[(2-azidoethoxy)methyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate | C22H28N6O6 | 详情 | 详情 | |
| (VI) | 31730 | 5-(aminocarbonyl)-2-[(2-azidoethoxy)methyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid | C18H20N6O6 | 详情 | 详情 | |
| (VII) | 18182 | 3-(4,4-diphenyl-1-piperidinyl)-1-propanamine; 3-(4,4-diphenyl-1-piperidinyl)propylamine | C20H26N2 | 详情 | 详情 | |
| (VIII) | 31731 | 2-[(2-azidoethoxy)methyl]-N(3)-[3-(4,4-diphenyl-1-piperidinyl)propyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxamide | C38H44N8O5 | 详情 | 详情 |