Identification of novel α7 nAChR positive allosteric modulators with the use of pharmacophore in silico screening methods

被引：8

作者：

Capelli, Anna Maria ^{[1
]}

Castelletti, Laura ^{[1
]}

Salvagno, Cristian ^{[1
]}

Oliosi, Beatrice ^{[1
]}

Di Lenarda, Elisa ^{[1
,3
]}

Virginio, Caterina ^{[1
]}

Lightfoot, Andrew ^{[2
]}

Kew, James N. C. ^{[2
]}

Teague, Simon ^{[2
]}

机构：

[1] GlaxoSmithKline, Mol Discovery Res, I-37135 Verona, Italy

[2] GlaxoSmithKline, Neurosci Ctr Excellence Drug Discovery, Harlow Nfsp, Essex, England

[3] Novartis Pharma Schweizerhalle, NIBR, CH-4133 Schweizerhall, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 15期

关键词：

Alpha7; nicotinic; Positive modulator; Pharmacophore; NICOTINIC ACETYLCHOLINE-RECEPTOR; AGONISTS; NEURONS; SCHIZOPHRENIA; INHIBITION; CALCIUM;

D O I：

10.1016/j.bmcl.2010.06.014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The pharmacophore model of in house potent and selective alpha 7 nAChR positive allosteric modulators is reported. The model was used to fish out commercially-available compounds from corporate 3D databases. As a result, novel alpha 7 positive modulator chemotypes were identified. A rat full PK profile of a representative compound is also described. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4561 / 4565

页数：5

共 24 条

[1] *ACC INC, CAT 4 10
[2] Schizophrenia, sensory gating, and nicotinic receptors
Adler, LE
Olincy, A
Waldo, M
Harris, JG
Griffith, J
Stevens, K
Flach, K
Nagamoto, H
Bickford, P
Leonard, S
Freedman, R
[J]. SCHIZOPHRENIA BULLETIN, 1998, 24 (02) : 189 - 202
[3] Albuquerque EX, 1998, TOXICOL LETT, V103, P211
[4] Choline is a selective agonist of α7 nicotnic acetylcholine receptors in the rat brain neurons
Alkondon, M
Pereira, EFR
Cortes, WS
Maelicke, A
Albuquerque, EX
[J]. EUROPEAN JOURNAL OF NEUROSCIENCE, 1997, 9 (12) : 2734 - 2742
[5] MUTATIONS AT 2 DISTINCT SITES WITHIN THE CHANNEL DOMAIN M2 ALTER CALCIUM PERMEABILITY OF NEURONAL ALPHA-7 NICOTINIC RECEPTOR
BERTRAND, D
GALZI, JL
DEVILLERSTHIERY, A
BERTRAND, S
CHANGEUX, JP
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (15) : 6971 - 6975
[6] Neuronal nicotinic acetylcholine receptor modulators: Recent advances and therapeutic potential
Breining, SR
Mazurov, AA
Miller, CH
[J]. ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 40, 2005, 40 : 3 - 16
[7] Activation and inhibition of the human α7 nicotinic acetylcholine receptor by agonists
Briggs, CA
McKenna, DG
[J]. NEUROPHARMACOLOGY, 1998, 37 (09) : 1095 - 1102
[8] Nitrogen substitution modifies the activity of cytisine on neuronal nicotinic receptor subtypes
Carbonnelle, E
Sparatore, F
Canu-Boido, C
Salvagno, C
Baldani-Guerra, B
Terstappen, G
Zwart, R
Vijverberg, H
Clementi, F
Gotti, C
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2003, 471 (02) : 85 - 96
[9] *DAYL INC, MULT FILT DAYL 4 71
[10] Frazier CJ, 1998, J NEUROSCI, V18, P8228

← 1 2 3 →