Evaluation of structurally diverse neuronal nicotinic receptor ligands for selectivity at the α6*subtype

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Breining, Scott R.¹  Bencherif, Merouane²  Grady, Sharon R.³  Whiteaker, Paul³  Marks, Michael J.³  Wageman, Charles R.³  Lester, Henry A.⁴  Yohannes, Daniel¹ 

[1] Targacept Inc, Dept Med Chem, Winston Salem, NC 27101 USA

[2] Targacept Inc, Preclin Res, Winston Salem, NC 27101 USA

[3] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA

[4] CALTECH, Div Biol, Pasadena, CA 91125 USA

关键词: Neuronal nicotinic receptor;    NNR;    Alpha 6;    a3b4;    SAR;    Pyrimidine;    Nicotinic acetylcholine receptor;    Smoking cessation;    Nicotine addiction;    Dopamine release;    Parkinson's disease;   

DOI  :  10.1016/j.bmcl.2009.05.085

来源: Elsevier

【 摘 要 】

Direct comparison of pyridine versus pyrimidine substituents on a small but diverse set of ligands indicates that the pyrimidine substitution has the potential to enhance affinity and/or functional activity at alpha 6 subunit-containing neuronal nicotinic receptors (NNRs) and decrease activation of ganglionic nicotinic receptors, depending on the scaffold. The rami. cations of this structure-activity relationship are discussed in the context of the design of small molecules targeting smoking cessation. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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