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    • 3. 发明申请
    • NOVEL TRPA1 ANTAGONISTS
    • 新一代TRPA1 ANTAGONISTS
    • WO2011043954A1
    • 2011-04-14
    • PCT/US2010/050493
    • 2010-09-28
    • MERCK SHARP & DOHME CORP.BILODEAU, Mark, T.EGBERTSON, MelissaGREEN, AhrenLI, YiweiHARTNETT, John, C.
    • BILODEAU, Mark, T.EGBERTSON, MelissaGREEN, AhrenLI, YiweiHARTNETT, John, C.
    • A61K31/555
    • C07C215/20A61K31/133C07C25/02C07C211/34C07C215/44C07C255/58C07C2602/10C07D215/38C07D215/44C07D311/74C07D311/76C07D405/04C07D405/06
    • The present invention relates to compositions and methods that modulate at least one TRP family member. Specifically, the present invention relates to novel TRPA1 antagonists and their use in the treatment of pain such as chronic inflammatory and neuropathic pain. Compounds that can modulate one or more TRPA1 functions are useful in many aspects including, but not limited to, maintaining calcium homeostasis; maintaining sodium homeostasis; modulating intracellular calcium levels; modulating membrane polarization (membrane potential); modulating cation levels; and/or treating or preventing diseases, disorders, or conditions associated with calcium homeostasis, sodium homeostasis, calcium or sodium dyshomeostasis, or membrane polarization/hyperpolarization (including hypo and hyperexcitability), and/or treating or preventing diseases, disorders, or conditions associated with regulation or misregulation of TRPA1 expression or function. The present invention further relates to methods and compositions that antagonize both a function of TRPA1 and a function of one or more additional TRP channels.
    • 本发明涉及调节至少一种TRP家族成员的组合物和方法。 具体地说,本发明涉及新型TRPA1拮抗剂及其用于治疗慢性炎性和神经性疼痛等疼痛的用途。 可以调节一种或多种TRPA1功能的化合物在许多方面是有用的,包括但不限于维持钙稳态; 维持钠稳态; 调节细胞内钙含量; 调节膜极化(膜电位); 调节阳离子水平; 和/或治疗或预防与钙稳态相关的疾病,病症或病症,钠稳态,钙或钠血管平衡,或膜极化/超极化(包括低钠和过度兴奋性)和/或治疗或预防与疾病,病症或病症相关 与TRPA1表达或功能调节或失调。 本发明还涉及拮抗TRPA1的功能和一种或多种另外的TRP通道的功能的方法和组合物。