72105-70-5Relevant academic research and scientific papers
Highly Selective and Potent α4β2 nAChR Antagonist Inhibits Nicotine Self-Administration and Reinstatement in Rats
Wu, Jinhua,Cippitelli, Andrea,Zhang, Yaohong,Debevec, Ginamarie,Schoch, Jennifer,Ozawa, Akihiko,Yu, Yongping,Liu, Huan,Chen, Wenteng,Houghten, Richard A.,Welmaker, Gregory S.,Giulianotti, Marc A.,Toll, Lawrence
, p. 10092 - 10104 (2017)
The α4β2 nAChR is the most predominant subtype in the brain and is a well-known culprit for nicotine addiction. Previously we presented a series of α4β2 nAChR selective compounds that were discovered from a mixture-based positional-scanning combinatorial library. Here we report further optimization identified highly potent and selective α4β2 nAChR antagonists 5 (AP-202) and 13 (AP-211). Both compounds are devoid of in vitro agonist activity and are potent inhibitors of epibatidine-induced changes in membrane potential in cells containing α4β2 nAChR, with IC50 values of approximately 10 nM, but are weak agonists in cells containing α3β4 nAChR. In vivo studies show that 5 can significantly reduce operant nicotine self-administration and nicotine relapse-like behavior in rats at doses of 0.3 and 1 mg/kg. The pharmacokinetic data also indicate that 5, via sc administration, is rapidly absorbed into the blood, reaching maximal concentration within 10 min with a half-life of less than 1 h.
Identification of a Hit Series of Antileishmanial Compounds through the Use of Mixture-Based Libraries
Giulianotti, Marc A.,Vesely, Brian A.,Azhari, Ala,Souza, Ashley,Lavoi, Travis,Houghten, Richard A.,Kyle, Dennis E.,Leahy, James W.
, p. 802 - 807 (2017)
From a screening campaign that included mixture-based libraries containing more than 6 million compounds, a lead series of bis-cyclic guanidines was identified as the most promising. Lead optimization resulted in the identification of potent (IC50 500 nM) and selective compounds within this series as well as potent and selective monoguanidines.
COMPOSITIONS, METHODS OF USE, AND METHODS OF TREATMENT
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Page/Page column 30-32, (2018/12/13)
The present disclosure provides compositions including a α4β2 nAChR antagonist, pharmaceutical compositions including a α4β2 nAChR antagonist, methods of making the compositions or pharmaceutical compositions, methods of treatment of a condition (e.g., nicotine addiction) or disease, methods of treatment using compositions or pharmaceutical compositions, and the like. Embodiments of the present disclosure can be used to reduce nicotine cravings and treat nicotine addiction. The compositions have selective affinity for the α4β2 receptor, which appears to be involved in nicotine dependence.
