2. Academic Validation
  3. Design, synthesis and discovery of picomolar selective α4β2 nicotinic acetylcholine receptor ligands

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

  • J Med Chem. 2013 Nov 14;56(21):8404-21. doi: 10.1021/jm4008455.
Venkata M Yenugonda 1,  Yingxian Xiao,  Edward D Levin,  Amir H Rezvani,  Thao Tran,  Nour Al-Muhtasib,  Niaz Sahibzada,  Teresa Xie,  Corinne Wells,  Susan Slade,  Joshua E Johnson,  Sivanesan Dakshanamurthy,  Hye-Sik Kong,  York Tomita,  Yong Liu,  Mikell Paige,  Kenneth J Kellar,  Milton L Brown
Affiliations

Affiliation

  • 1 Center for Drug Discovery, Georgetown University Medical Center , 3970 Reservoir Road NW, Research Building, EP-07, Washington, D.C. 20057, United States.
PMID: 24047231 DOI: 10.1021/jm4008455
Abstract

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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z