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【结 构 式】 
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【药物名称】NNC-21-0136 【化学名称】2-Chloro-N6-[2-(2-benzothiazolylsulfanyl)-1(R)-methylethyl]adenosine 【CA登记号】162684-35-7 【 分 子 式 】C20H21ClN6O4S2 【 分 子 量 】509.00917 |
【开发单位】Novo Nordisk (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Adenosine A1 Agonists |
合成路线1
Protection of D-alaninol (I) with di-tert-butyl dicarbonate gave rise to carbamate (II). Subsequent Mitsunobu coupling of (II) with 2-mercaptobenzothiazole (III) furnished thioether (IV), which was deprotected with HCl in EtOAc. The resulting amine (V) was condensed with dichloropurine (VI) to afford the chloroadenosine derivative (VII). Finally, cleavage of the acetate esters of (VII) was achieved by treatment with NaOMe in MeOH.
| 【1】 Lau, J.; Judge, M.E.; Sheardown, M.J.; Petersen, H.; Shalmi, M.; Knutsen, L.J.S.; Hansen, A.J.; Thomsen, C.; Weis, J.U.; N-substituted adenosines as novel neuroprotective A1 agonists with diminished hypotensive effects. J Med Chem 1999, 42, 18, 3463. |
| 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) | 21414 | (2R)-2-Amino-1-propanol; D-Alaninol; D-(-)-Alaninol | 35320-23-1 | C3H9NO | 详情 | 详情 |
| (II) | 31758 | tert-butyl (1R)-2-hydroxy-1-methylethylcarbamate | C8H17NO3 | 详情 | 详情 | |
| (III) | 24677 | 1,3-benzothiazol-2-ylhydrosulfide | 149-30-4 | C7H5NS2 | 详情 | 详情 |
| (IV) | 31759 | tert-butyl (1R)-2-(1,3-benzothiazol-2-ylsulfanyl)-1-methylethylcarbamate | C15H20N2O2S2 | 详情 | 详情 | |
| (V) | 31760 | (2R)-1-(1,3-benzothiazol-2-ylsulfanyl)-2-propanamine; (1R)-2-(1,3-benzothiazol-2-ylsulfanyl)-1-methylethylamine | C10H12N2S2 | 详情 | 详情 | |
| (VI) | 25228 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H16Cl2N4O7 | 详情 | 详情 | |
| (VII) | 31761 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1R)-2-(1,3-benzothiazol-2-ylsulfanyl)-1-methylethyl]amino]-2-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C26H27ClN6O7S2 | 详情 | 详情 |
Extended Information