| Title : Design, synthesis and discovery of picomolar selective alpha4beta2 nicotinic acetylcholine receptor ligands - Yenugonda_2013_J.Med.Chem_56_8404 |
| Author(s) : Yenugonda VM , Xiao Y , Levin ED , Rezvani AH , Tran T , Al-Muhtasib N , Sahibzada N , Xie T , Wells C , Slade S , Johnson JE , Dakshanamurthy S , Kong HS , Tomita Y , Liu Y , Paige M , Kellar KJ , Brown ML |
| Ref : Journal of Medicinal Chemistry , 56 :8404 , 2013 |
|
Abstract :
Developing novel and selective compounds that desensitize alpha4beta2 nicotinic acetylcholine receptors (nAChRs) could provide new effective treatments for nicotine addiction, as well as other disorders. Here we report a new class of nAChR ligands that display high selectivity and picomolar binding affinity for alpha4beta2 nicotinic receptors. The novel compounds have Ki values in the range of 0.031-0.26 nM and properties that should make them good candidates as drugs acting in the CNS. The selected lead compound 1 (VMY-2-95) binds with high affinity and potently desensitizes alpha4beta2 nAChRs. At a dose of 3 mg/kg, compound 1 significantly reduced rat nicotine self-administration. The overall results support further characterizations of compound 1 and its analogues in preclinical models of nicotine addiction and perhaps other disorders involving nAChRs. |
| PubMedSearch : Yenugonda_2013_J.Med.Chem_56_8404 |
| PubMedID: 24047231 |
Yenugonda VM, Xiao Y, Levin ED, Rezvani AH, Tran T, Al-Muhtasib N, Sahibzada N, Xie T, Wells C, Slade S, Johnson JE, Dakshanamurthy S, Kong HS, Tomita Y, Liu Y, Paige M, Kellar KJ, Brown ML (2013)
Design, synthesis and discovery of picomolar selective alpha4beta2 nicotinic acetylcholine receptor ligands
Journal of Medicinal Chemistry
56 :8404
Yenugonda VM, Xiao Y, Levin ED, Rezvani AH, Tran T, Al-Muhtasib N, Sahibzada N, Xie T, Wells C, Slade S, Johnson JE, Dakshanamurthy S, Kong HS, Tomita Y, Liu Y, Paige M, Kellar KJ, Brown ML (2013)
Journal of Medicinal Chemistry
56 :8404