Scholars@Duke
Journal cover image

Design, synthesis and discovery of picomolar selective α4β2 nicotinic acetylcholine receptor ligands.

Publication ,  Journal Article
Yenugonda, VM; Xiao, Y; Levin, ED; Rezvani, AH; Tran, T; Al-Muhtasib, N; Sahibzada, N; Xie, T; Wells, C; Slade, S; Johnson, JE; Kong, H-S ...
Published in: J Med Chem
November 14, 2013
Published version (DOI) Link to item

Developing novel and selective compounds that desensitize α4β2 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 α4β2 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 α4β2 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.

Duke Scholars

Edward Daniel Levin
Author Edward Daniel Levin Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...
Amir H. Rezvani
Author Amir H. Rezvani Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...

Published In

J Med Chem

DOI

10.1021/jm4008455

EISSN

1520-4804

Publication Date

November 14, 2013

Volume

56

Issue

21

Start / End Page

8404 / 8421

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Software
  • Receptors, Nicotinic
  • Pyridines
  • Molecular Structure
  • Models, Molecular
  • Medicinal & Biomolecular Chemistry
  • Ligands
  • Humans
  • Drug Discovery
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yenugonda, V. M., Xiao, Y., Levin, E. D., Rezvani, A. H., Tran, T., Al-Muhtasib, N., … Brown, M. L. (2013). Design, synthesis and discovery of picomolar selective α4β2 nicotinic acetylcholine receptor ligands. J Med Chem, 56(21), 8404–8421. https://doi.org/10.1021/jm4008455
Yenugonda, Venkata M., Yingxian Xiao, Edward D. Levin, Amir H. Rezvani, Thao Tran, Nour Al-Muhtasib, Niaz Sahibzada, et al. “Design, synthesis and discovery of picomolar selective α4β2 nicotinic acetylcholine receptor ligands.” J Med Chem 56, no. 21 (November 14, 2013): 8404–21. https://doi.org/10.1021/jm4008455.
Yenugonda VM, Xiao Y, Levin ED, Rezvani AH, Tran T, Al-Muhtasib N, et al. Design, synthesis and discovery of picomolar selective α4β2 nicotinic acetylcholine receptor ligands. J Med Chem. 2013 Nov 14;56(21):8404–21.
Yenugonda, Venkata M., et al. “Design, synthesis and discovery of picomolar selective α4β2 nicotinic acetylcholine receptor ligands.” J Med Chem, vol. 56, no. 21, Nov. 2013, pp. 8404–21. Pubmed, doi:10.1021/jm4008455.
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 H-S, Tomita Y, Liu Y, Paige M, Kellar KJ, Brown ML. Design, synthesis and discovery of picomolar selective α4β2 nicotinic acetylcholine receptor ligands. J Med Chem. 2013 Nov 14;56(21):8404–8421.
Journal cover image

Published In

J Med Chem

DOI

10.1021/jm4008455

EISSN

1520-4804

Publication Date

November 14, 2013

Volume

56

Issue

21

Start / End Page

8404 / 8421

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Software
  • Receptors, Nicotinic
  • Pyridines
  • Molecular Structure
  • Models, Molecular
  • Medicinal & Biomolecular Chemistry
  • Ligands
  • Humans
  • Drug Discovery