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【结 构 式】 
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【药物名称】Bropirimine, PNU-54461, U-54461, ABPP, Remisar 【化学名称】2-Amino-5-bromo-6-phenyl-4(3H)-pyrimidinone 【CA登记号】56741-95-8 【 分 子 式 】C10H8BrN3O 【 分 子 量 】266.09876 |
【开发单位】Pfizer (Originator), Yakult Honsha (Licensee) 【药理作用】Bladder Cancer Therapy , IMMUNOMODULATING AGENTS, Immunostimulants, Oncolytic Drugs, Interferon Inducers |
合成路线1
ABPP is a phenylpyrimidinone and as such is prepared in high yield by condensation of guanidine with ethyl benzoylacetate. Ethyl benzoylacetate is commercially available and can also be prepared in high yield by condensation of dilithiomonoethylmalonate at 78 C with benzoyl chloride. Reaction of the resultant beta-ketoester with guanidine in refluxing ethanol affords its pyrimidinone in high yield. ABPP can be prepared from this pyrimidinone by bromination in acetic acid at room temperature. Similarly, iodine can be introduced at this step to afford the iodo analogue, AIPP. The overall yield of these pyrimidinones from monoethylmalonate is generally) 50%.
| 【1】 Fitzpatrick, F.A.; Wynalda, M.A.; High-perfomance liquid chromatographic determination of 5-halopyrimidinone interferon inducers. Anal Chem 1982, 17, 151. |
| 【2】 Skulnick, H.I.; Stringfellow, D.A.; Wierenga, W.; Weed, S.D.; Antiviral and interferon induction stucture-activity relationship profile of 6-aryl-pyrimidines. Am Soc Microbiol 1980, 2, 1402-1404. |
| 【3】 Brown, T.B.; Stevens, M.F.G.; Triazines and related products. XV. 2,4-Diaminopyrimidines and 2-aminopyrimidin-4(3H)-ones bearing 1,2,3-benzotriazinyl groups as potential dihydrofolic reductase inhibitors. J Chem Soc - Perkins Trans I 1975, 11, 1023-1028. |
| 【4】 Wierenga, W.; Skulnick, H.I.; J Org Chem 1979, 44, 310. |
| 【5】 Stringfellow, D.A.; Eidson, E.E.; Wierenga, W.; Skulnick, H.I.; Renis, H.E.; Weed, S.D.; 5-Substituted 2-amino-6-phenyl-4(3H)-pyrimidinones. Antiviral- and interferon-inducing agents. J Med Chem 1980, 23, 3, 237-239. |
| 【6】 Wierenga, W.; ABPP. Drugs Fut 1984, 9, 8, 567. |