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    • 4. 发明申请
    • POLYCYCLIC DIAZODIOXIDE-BASED BCL-2 PROTEIN ANTAGONIST
    • 多基于二氧化物的BCL-2蛋白质拮抗剂
    • WO2004099162A1
    • 2004-11-18
    • PCT/US2004/013513
    • 2004-04-30
    • RICERCA BIOSCIENCES, LLC.GUPTA, SandeepRAJAGOPALAN, RaghavanCARRIG, David, MichaelFERNANDES, Prabhavathi
    • GUPTA, SandeepRAJAGOPALAN, RaghavanCARRIG, David, MichaelFERNANDES, Prabhavathi
    • C07D245/04
    • C07D401/12C07D245/04C07D339/00
    • Compounds of Formula 8 are provided: A and B are each independently selected from the group consisting of -NO-, -SO-, and - NR 9 -. C is a single bond or a double bond. D is selected from the group consisting of single bond, E is selected from the group consisting of single bond, double bond, -NR 9 -, -0-, -S-, -SO- and -S0 2 -; and m and n are each independently an integer from 0 to 6. R 1 to R 9 are appropriately selected to optimize physicochemical and/or biological properties such as lipophilicity, bioavailability, pharmacokinetics, Bcl-2 and Bcl-X L activities, metabolism, and the like. R 1 and R 2 , R 2 and R 3 , R 3 and R 4 , R 5 and R 6 , R 6 and R 7 , or R 7 and R 8 may optionally be joined together to form an aromatic or heteroaromatic ring, including, but not limited to, naphthyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl and the like. The compounds are useful for tumor therapeutic applications. These compounds induce apoptosis in tumor cells mediated through Bcl-2 family of proteins.
    • 提供式8的化合物:A和B各自独立地选自-NO - , - SO - 和 - NR 9 - 。 C是单键或双键。 D选自单键,E选自单键,双键,-NR 9 - , - O - , - S - , - SO-和-SO 2 - 。 并且m和n各自独立地为0至6的整数.R 1至R 9适当地选择以优化物理化学和/或生物学性质,例如亲脂性,生物利用度,药代动力学,Bcl-2和Bcl-XL活性 ,新陈代谢等。 R 1和R 2,R 3和R 3,R 3,R 4,R 5和R 6, R 6,R 7和R 7可以任选地连接在一起形成芳族或杂芳族环,包括但不限于萘基,喹啉基,异喹啉基,苯并咪唑基,苯并恶唑基, 苯并噻唑基等。 这些化合物可用于肿瘤治疗应用。 这些化合物诱导通过蛋白Bcl-2家族介导的肿瘤细胞凋亡。