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    • 10. 发明申请
    • SORTASE A INHIBITORS
    • 输入一个抑制剂
    • WO2011028492A2
    • 2011-03-10
    • PCT/US2010046394
    • 2010-08-23
    • UNIV CALIFORNIAJUNG MICHAEL ECLUBB ROBERT TYI SUNG WOOKSUREE NUTTEECLEMENS JEREMY JUSTIN
    • JUNG MICHAEL ECLUBB ROBERT TYI SUNG WOOKSUREE NUTTEECLEMENS JEREMY JUSTIN
    • A61K31/501
    • C07D237/12C07D231/18C07D231/26C07D237/14C07D237/18C07D277/32C07D277/34C07D277/36C07D417/06
    • Bacterial infections, including Methicillin resistant Staphylococcus aureus (MRSA) infections are a major health problem that has created a pressing need for new antibiotics. Pyridazinone, rhodanine, and pyrazolethione compounds effective inhibit the enzymatic activity of sortase A (srtA) found in gram positive bacteria are disclosed. A structure activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC50 values in the sub-micromolar range. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Many of these molecules also inhibit the sortase enzyme from B. anthracis suggesting that they may be generalized sortase inhibitors. The novel compounds, compositions, uses, formulations, medicaments, articles of manufacture provide improved materials, uses, and treatments useful in combating infectious disorders.
    • 细菌感染,包括耐甲氧西林金黄色葡萄球菌(MRSA)感染是一个主要的健康问题,迫切需要新的抗生素。 公开了有效抑制革兰氏阳性细菌中分泌酶A(srtA)的酶活性的哒嗪酮,绕丹宁和吡唑硫酮化合物。 结构活动关系(SAR)分析导致了几种抑制SrtA的哒嗪酮和吡唑硫酮类似物的鉴定,其IC50值在亚微摩尔范围内。 抑制金黄色葡萄球菌SrtA分选酶的化合物可以作为有效的抗感染剂起作用,因为该酶将毒力因子附着在细胞壁上。 这些分子中的许多还抑制炭疽杆菌分选酶,表明它们可以是广义分解酶抑制剂。 新型化合物,组合物,用途,制剂,药物,制品提供改善的材料,用途和用于对抗传染病的治疗。