Synthesis and pharmacological characterization of new neuronal nicotinic acetylcholine receptor ligands derived from Sazetidine-A

被引：4

作者：

Liu, Yong ^{[1
]}

Paige, Mike ^{[1
]}

Olson, Thao T. ^{[2
]}

Al-Muhtasib, Nour ^{[2
]}

Xie, Teresa ^{[2
]}

Hou, Shujie ^{[1
]}

White, Michael P. ^{[1
]}

Cordova, Antoinette ^{[1
]}

Guo, Jessica L. ^{[1
]}

Kellar, Kenneth J. ^{[2
]}

Xiao, Yingxian ^{[2
]}

Brown, Milton L. ^{[1
]}

机构：

[1] Georgetown Univ, Med Ctr, Ctr Drug Discovery, Washington, DC 20057 USA

[2] Georgetown Univ, Sch Med, Dept Physiol & Pharmacol, Washington, DC 20057 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 13期

关键词：

Sazetidine A; nAChR alpha 4 beta 2; Nicotinic receptor; Click chemistry; Bioisostere; Biostere; Photoaffinity label; SUSTAINED-RELEASE BUPROPION; RANDOMIZED CONTROLLED-TRIAL; PARTIAL AGONIST; DESENSITIZING AGENT; SMOKING-CESSATION; ANALGESIC AGENT; ALPHA-4-BETA-2; POTENT; VARENICLINE; BINDING;

D O I：

10.1016/j.bmcl.2014.04.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The enantiomers of two analogs of Sazetidine-A as well as several other novel biosteric analogues were synthesized. Their binding affinities at three major nAChRs subtypes and selectivity profiles were determined. Though many (S)-enantiomers of Sazetidine-A analogs have high binding affinities and good subtype selectivities, it is not a general rule that (S)-enantiomers are better than their (R) counterparts. Compound 11, of which the ethynyl group was replaced by its' bioisostere-the triazole via click chemistry, showed a high binding affinity to alpha 4 beta 2 subtype (K-1 = 1.3 nM) and better selectivity to the alpha 4 beta 2 subtype over alpha 3 beta 4 subtype with that of Sazetidine-A. The azide compound 15, a potential photoaffinity label, showed improved high selectivity and similar binding property profile with that of Sazetidine-A. The biaryl analog 17 exhibited a much lower affinity as compared to Sazetidine-A indicating the importance of a 'long tail' side chain for alpha 4 beta 2 nAChR binding. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：2954 / 2956

页数：3

共 31 条

[11] Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation -: A randomized controlled trial
Jorenby, Douglas E.
Hays, J. Taylor
Rigotti, Nancy A.
Azoulay, Salomon
Watsky, Eric J.
Williams, Kathryn E.
Billing, Clare B.
Gong, Jason
Reeves, Karen R.
[J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 296 (01): : 56 - 63
[12] Sazetidine-A, a Selective α4β2 Nicotinic Receptor Desensitizing Agent and Partial Agonist, Reduces Nicotine Self-Administration in Rats
Levin, Edward D.
Rezvani, Amir H.
Xiao, Yingxian
Slade, Susan
Cauley, Marty
Wells, Corinne
Hampton, Dawn
Petro, Ann
Rose, Jed E.
Brown, Milton L.
Paige, Mikell A.
McDowell, Brian E.
Kellar, Kenneth J.
[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2010, 332 (03) : 933 - 939
[13] Lin N., 1997, US Patent, Patent No. [1997/5629325, 19975629325]
[14] Chemistry and Pharmacological Studies of 3-Alkoxy-2,5-Disubstituted-Pyridinyl Compounds as Novel Selective α4β2 Nicotinic Acetylcholine Receptor Ligands That Reduce Alcohol Intake in Rats
Liu, Yong
Richardson, Janell
Thao Tran
Al-Muhtasib, Nour
Xie, Teresa
Yenugonda, Venkata Mahidhar
Sexton, Hannah G.
Rezvani, Amir H.
Levin, Edward D.
Sahibzada, Niaz
Kellar, Kenneth J.
Brown, Milton L.
Xiao, Yingxian
Paige, Mikell
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (07) : 3000 - 3011
[15] Varenicline Is a Potent Agonist of the Human 5-Hydroxytryptamine3 Receptor
Lummis, S. C. R.
Thompson, A. J.
Bencherif, M.
Lester, H. A.
[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2011, 339 (01) : 125 - 131
[16] Varenicline is a partial agonist at α4β2 and a full agonist at α7 neuronal nicotinic receptors
Mihalak, Karla B.
Carroll, F. Ivy
Luetje, Charles W.
[J]. MOLECULAR PHARMACOLOGY, 2006, 70 (03) : 801 - 805
[17] Suicidal Behavior and Depression in Smoking Cessation Treatments
Moore, Thomas J.
Furberg, Curt D.
Glenmullen, Joseph
Maltsberger, John T.
Singh, Sonal
[J]. PLOS ONE, 2011, 6 (11):
[18] Synthesis and Nicotinic Acetylcholine Receptor in Vitro and in Vivo Pharmacological Properties of 2′-Fluoro-3′-(substituted phenyl)deschloroepibatidine Analogues of 2′-Fluoro-3′-(4-nitrophenyl)deschloroepibatidine
Ondachi, Pauline
Castro, Ana
Luetje, Charles W.
Damaj, M. Imad
Mascarella, S. Wayne
Navarro, Hernan A.
Carroll, F. Ivy
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (14) : 6512 - 6522
[19] Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats
Rezvani, Amir H.
Cauley, Marty
Sexton, Hannah
Xiao, Yingxian
Brown, Milton L.
Paige, Mikell A.
McDowell, Brian E.
Kellar, Kenneth J.
Levin, Edward D.
[J]. PSYCHOPHARMACOLOGY, 2011, 215 (04) : 621 - 630
[20] Effects of sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats
Rezvani, Amir H.
Slade, Susan
Wells, Cori
Petro, Ann
Lumeng, Lawrence
Li, Ting-Kai
Xiao, Yingxian
Brown, Milton L.
Paige, Mikell A.
McDowell, Brian E.
Rose, Jed E.
Kellar, Kenneth J.
Levin, Edward D.
[J]. PSYCHOPHARMACOLOGY, 2010, 211 (02) : 161 - 174

← 1 2 3 4 →