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【结 构 式】 
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【药物名称】MW01-070C 【化学名称】2-[11-Oxo-11-[4-(2-pyrimidinyl)piperazin-1-yl]undecyl]-2,3,5,6-tetrahydrobenzo[h]cinnolin-3-imine 【CA登记号】 【 分 子 式 】C31H41N7O 【 分 子 量 】527.71872 |
【开发单位】Northwestern University (Originator), Université Louis Pasteur (Originator) 【药理作用】Alzheimer's Dementia, Treatment of , Cerebrovascular Diseases, Treatment of, Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, IL-1beta Production Inhibitors, Inducible Nitric Oxide Synthase (NOS-2) Inhibitors, Nitric Oxide Production Inhibitors |
合成路线1
The condensation of 1-tetralone (I) with 2-oxoacetic acid (II) by means of KOH gives 2-(1-oxo-1,2,3,4-tetrahydronaphthalen-2-ylidene)acetic acid (III), which is cyclized with hydrazine in hot butanol to yield the tricyclic pyridazinone (IV). The treatment of (IV) with hot POCl3 gives the chloropyridazine derivative (V), which is treated with hydrazine in boiling water to provide the hydrazino derivative (VI). The hydrogenation of (VI) with H2 over Ni in methanol gives the aminopyridazine derivative (VII), which is condensed with ethyl 11-bromoundecanoate (VIII) (prepared by esterification of the corresponding acid (IX) with Et-OH/HCl) in hot DMF to yield the adduct (X). The hydrolysis of (X) with HCl in hot HOAc affords the corresponding acid (XI), which is finally condensed with 1-(2-pyrimidinyl)piperazine (XII) by means of HOBt and EDC in DMF to provide the target amide.
| 【1】 Mirzoeva, S.; Zasadzki, M.; Sawkar, A.; et al.; Discovery of a 3-amino-6-phenyl-pyridazine derivative as a new synthetic antineuroinflammatory compound. J Med Chem 2002, 45, 3, 563. |
| 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) | 20720 | 3,4-dihydro-1(2H)-naphthalenone | 529-34-0 | C10H10O | 详情 | 详情 |
| (II) | 15618 | 2-Oxoacetic acid; Glyoxylic Acid | 298-12-4 | C2H2O3 | 详情 | 详情 |
| (III) | 56768 | 2-[1-oxo-3,4-dihydro-2(1H)-naphthalenylidene]acetic acid | C12H10O3 | 详情 | 详情 | |
| (IV) | 56769 | 5,6-dihydrobenzo[h]cinnolin-3(2H)-one | C12H10N2O | 详情 | 详情 | |
| (V) | 56770 | 3-chloro-5,6-dihydrobenzo[h]cinnoline | C12H9ClN2 | 详情 | 详情 | |
| (VI) | 56771 | 3-hydrazino-5,6-dihydrobenzo[h]cinnoline | C12H12N4 | 详情 | 详情 | |
| (VII) | 56772 | 5,6-dihydrobenzo[h]cinnolin-3-ylamine; 5,6-dihydrobenzo[h]cinnolin-3-amine | C12H11N3 | 详情 | 详情 | |
| (VIII) | 56773 | Ethyl omega-bromoundecanoate; Ethyl 11-bromoundecanoate | 6271-23-4 | C13H25BrO2 | 详情 | 详情 |
| (IX) | 56774 | 11-Bromoundecanoic acid | 2834-05-1 | C11H21BrO2 | 详情 | 详情 |
| (X) | 56775 | ethyl 11-[3-imino-5,6-dihydrobenzo[h]cinnolin-2(3H)-yl]undecanoate | C25H35N3O2 | 详情 | 详情 | |
| (XI) | 56776 | 11-[3-imino-5,6-dihydrobenzo[h]cinnolin-2(3H)-yl]undecanoic acid | C23H31N3O2 | 详情 | 详情 | |
| (XII) | 11175 | 2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine | 20980-22-7 | C8H12N4 | 详情 | 详情 |