Structure-Activity Relationship Studies of Sulfonylpiperazine Analogues as Novel Negative Allosteric Modulators of Human Neuronal Nicotinic Receptors

作者：Henderson Brandon J; Carper Daniel J; Gonzalez Cestari Tatiana F; Yi Bitna; Mahasenan Kiran; Pavlovicz Ryan E; Dalefield Martin L; Coleman Robert S; Li Chenglong; McKay Dennis B^*

来源：Journal of Medicinal Chemistry, 2011, 54(24): 8681-8692.

DOI：10.1021/jm201294r

Neuronal nicotinic receptors have been implicated in several diseases and disorders such as autism, Alzheimer's disease, Parkinson's disease, epilepsy, and various forms of addiction. To understand the role of nicotinic receptors in these conditions, it would be beneficial to have selective molecules that target specific nicotinic receptors in vitro and in vivo. Our laboratory has previously identified novel negative allosteric modulators of human alpha 4 beta 2 (H alpha 4 beta 2) and human alpha 3 beta 4 (H alpha 3 beta 4) nicotinic receptors. The effects of novel sulfonylpiperazine analogues that act as negative allosteric modulators on both H alpha 4 beta 2 nAChRs and H alpha 3 beta 4 nAChRs were investigated. This work, through structure activity relationship (SAR) studies, describes the chemical features of these molecules that are important for both potency and selectivity on H alpha 4 beta 2 nAChRs.

• 出版日期2011-12-22