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【结 构 式】 
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【药物名称】NNC-26-9100 【化学名称】N-[3-[N-(5-Bromo-2-pyridyl)-N-(3,4-dichlorobenzyl)amino]propyl]-N'-[3-(1H-imidazol-4-yl)propyl]thiourea 【CA登记号】199522-35-5 【 分 子 式 】C22H25BrCl2N6S 【 分 子 量 】556.35875 |
【开发单位】Novo Nordisk (Originator) 【药理作用】Antiglaucoma Agents, OCULAR MEDICATIONS, Ophthalmic Drugs, Somatostatin srif2B (sst4) Agonists |
合成路线1
Reaction of 2,5-dibromopyridine (I) with an excess of 1,3-diaminopropane (II) in refluxing pyridine provided N-1-(2-pyridyl)propanediamine (III). This compound was further alkylated at the 1N with 3,4-dichlorobenzyl chloride (IV) in DMSO using NaH as the base to afford (V). From this, isothiocyanate (VI) was prepared by reaction with CS2 and DCC in THF. Subsequent coupling with trityl-protected amine (VII) yielded the thiourea (VIII). Finally, the trityl protecting group was removed by refluxing in 1 N HCl.
| 【1】 Liu, S.; Tang, C.; Ho, B.; Ankersen, M.; Stidsen, C.E.; Crider, A.M.; Nonpeptide somatostatin agonists with sst4 selectivity: Synthesis and structure-activity relationships of thioureas. J Med Chem 1998, 41, 24, 4693. |
| 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) | 19330 | 2,5-dibromopyridine | 624-28-2 | C5H3Br2N | 详情 | 详情 |
| (II) | 19331 | 3-aminopropylamine; 1,3-propanediamine | 109-76-2 | C3H10N2 | 详情 | 详情 |
| (III) | 19332 | N-(3-aminopropyl)-N-(5-bromo-2-pyridinyl)amine; N(1)-(5-bromo-2-pyridinyl)-1,3-propanediamine | C8H12BrN3 | 详情 | 详情 | |
| (IV) | 19333 | 1,2-dichloro-4-(chloromethyl)benzene | 102-47-6 | C7H5Cl3 | 详情 | 详情 |
| (V) | 19334 | N(1)-(5-bromo-2-pyridinyl)-N(1)-(3,4-dichlorobenzyl)-1,3-propanediamine; N-(3-aminopropyl)-N-(5-bromo-2-pyridinyl)-N-(3,4-dichlorobenzyl)amine | C15H16BrCl2N3 | 详情 | 详情 | |
| (VI) | 19335 | N-(5-bromo-2-pyridinyl)-N-(3,4-dichlorobenzyl)-N-(3-isothiocyanatopropyl)amine; 5-bromo-N-(3,4-dichlorobenzyl)-N-(3-isothiocyanatopropyl)-2-pyridinamine | C16H14BrCl2N3S | 详情 | 详情 | |
| (VII) | 19336 | 3-(1-trityl-1H-imidazol-4-yl)-1-propanamine; 3-(1-trityl-1H-imidazol-4-yl)propylamine | C25H25N3 | 详情 | 详情 | |
| (VIII) | 19337 | N-[3-[(5-bromo-2-pyridinyl)(3,4-dichlorobenzyl)amino]propyl]-N'-[3-(1-trityl-1H-imidazol-4-yl)propyl]thiourea | C41H39BrCl2N6S | 详情 | 详情 |