- 专利标题: 3-hydroxypyrimidine-2,4-dione-5-carboxamides as potent inhibitors of HIV
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申请号: US15553508申请日: 2016-03-03
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公开(公告)号: US10117871B2公开(公告)日: 2018-11-06
- 发明人: Zhengqiang Wang
- 申请人: Regents of the University of Minnesota
- 申请人地址: US MN Minneapolis
- 专利权人: Regents of the University of Minnesota
- 当前专利权人: Regents of the University of Minnesota
- 当前专利权人地址: US MN Minneapolis
- 代理机构: Schwegman Lundberg & Woessner, P.A.
- 国际申请: PCT/US2016/020751 WO 20160303
- 国际公布: WO2016/141220 WO 20160909
- 主分类号: A61K31/513
- IPC分类号: A61K31/513 ; C07D239/557 ; A61K31/03
摘要:
Various embodiments described herein are directed to compounds of formula (I), (II), (III) or (IV) for use as potent inhibitors of HIV integrase and for treatment of patients afflicted with AIDS. A major challenge of human immunodeficiency virus (HIV) chemotherapy continues to be the inevitable selection of resistance by the virus towards known drug regimens. Treating resistant HIV strains calls for novel antivirals with unique structural cores. Some embodiments are directed to compounds featuring a 3-hydroxypyrimidine-2,4-dione-5-carboxamide core that consistently confers low nanomolar potencies against HIV-1 in cell culture. Biochemical testing and molecular modeling results corroborate an antiviral mechanism of action of inhibiting integrase strand transfer (INST). Preliminary testing against raltegravir-resistant HIVs showed marginal cross resistance, suggesting that the chemotypes of the various embodiments described herein could fit an inhibitory profile of second generation INSTIs.
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