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Design, synthesis and structure-activity relationship of N-substituted tropane muscarinic acetylcholine receptor antagonists

  作者 Laine, DI; Yan, HX; Xie, HB; Davis, RS; Dufour, J; Widdowson, KL; Palovich, MR; Wan, ZH; Foley, JJ; Schmidt, DB; Hunsberger, GE; Burman, M; Bacon, AM; Webb, EF; Luttmann, MA; Salmon, M; Sarau, HM; Umbrecht, ST; Landis, PS; Peck, BJ; Busch-Petersen, J  
  选自 期刊  Bioorganic & Medicinal Chemistry Letters;  卷期  2012年22-9;  页码  3366-3369  
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[摘要]A novel series of N-substituted tropane derivatives was characterized as potent muscarinic acetylcholine receptor antagonists (mAChRs). Kinetic washout studies showed that the N-endosubstituted analog 24 displayed much slower reversibility at mAChRs than the methyl-substituted parent molecule darotropium. In addition, it was shown that this characteristic appeared to translate into enhanced which duration of action in a mouse model of bronchonstriction. (C) 2012 Elsevier Ltd. All rights reserved.

 
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