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    • 12. 发明申请
    • SUB-TYPE SELECTIVE AZABICYCLOALKANE DERIVATIVES
    • 亚型选择性亚硫酰胆碱衍生物
    • US20100173968A1
    • 2010-07-08
    • US12593779
    • 2008-03-27
    • Philip S. HammondAnatoly MazurovYun-De XiaoSrinivasa V. MurthySrinivisa Rao Akireddy
    • Philip S. HammondAnatoly MazurovYun-De XiaoSrinivasa V. MurthySrinivisa Rao Akireddy
    • A61K31/403C07D209/52A61P25/18A61P25/28
    • C07D209/52C07D221/22C07D401/06C07D401/12C07D403/06C07D405/06C07D405/12C07D413/06
    • Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide, ketone, and ester compounds prepared from certain azabicycloalkane carboxylic acids. The resulting compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α4β2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, such as those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).
    • 公开了化合物,包括该化合物的药物组合物,及其制备和使用方法。 这些化合物是由某些氮杂双环烷烃羧酸制备的酰胺,酮和酯化合物。 所得化合物对中枢神经系统(CNS)中α4和bgr2亚型的神经元烟碱受体表现出选择性并且以高亲和力结合。 化合物和组合物可用于治疗和/或预防各种各样的病症或病症,例如以烟碱型胆碱能神经传递功能障碍为特征的疾病,包括涉及神经递质释放的神经调节的疾病,例如多巴胺释放。 其特征在于正常神经递质释放的改变的CNS疾病是可以治疗和/或预防的疾病的另一个例子。 化合物可以:(i)改变患者脑部烟碱性胆碱能受体的数量,(ii)显示出神经保护作用,和(iii)当以有效量使用时,不会产生明显的不良副作用 因为血压和心率的显着增加,对胃肠道的显着的负面影响和对骨骼肌的显着影响)。