Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists

被引：29

作者：

Zarantonello, Paola ^{[1
]}

Bettini, Ezio

Paio, Alfredo ^{[1
]}

Simoncelli, Chiara ^{[1
]}

Terreni, Silvia ^{[1
]}

Cardullo, Francesco ^{[1
]}

机构：

[1] GlaxoSmithKline Med Res Ctr, Neurosci Ctr Excellence Drug Discovery, Dept Med Chem, I-37135 Verona, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 07期

关键词：

Ketamine; Phencyclidine; NMDA receptor; SUBUNIT COMPOSITION; TERTIARY ALKYL; DERIVATIVES; KETONE; AMINONITRILES; SCHIZOPHRENIA; INHIBITION; ADDITIONS; CHANNELS; DOPAMINE;

D O I：

10.1016/j.bmcl.2011.02.009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The identification of structurally novel analogues of ketamine and phencyclidine (PCP), as NMDA receptor antagonists, with low to moderate potency at GluN2A and GluN2B receptors is discussed. In particular, some examples, such as compounds 6 and 10, shows decreased calculated lipophilicity, when compared to PCP, while retaining moderate activity. Moreover, the germinal aryl amino substituted lactam ring, as exemplified in compounds 7-10 and 11-13, constitutes a novel scaffold with potential application in the design of biologically active compounds. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2059 / 2063

页数：5

共 58 条

[1]

ALVARO G, 2007, Patent No. 07042240

[2] Ketamine: New indications for an old drug [J].

Annetta, MG ;

Iemma, D ;

Garisto, C ;

Tafani, C ;

Proietti, R .

CURRENT DRUG TARGETS, 2005, 6 (07) :789-794

[3] X=Y-ZH SYSTEMS AS POTENTIAL 1,3-DIPOLES .5. INTRAMOLECULAR CYCLO-ADDITIONS OF IMINES OF ALPHA-AMINO-ACID ESTERS [J].

ARMSTRONG, P ;

GRIGG, R ;

JORDAN, MW ;

MALONE, JF .

TETRAHEDRON, 1985, 41 (17) :3547-3558

[4] Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase [J].

Behrens, M. Margarita ;

Ali, Sameh S. ;

Dao, Diep N. ;

Lucero, Jacinta ;

Shekhtman, Grigoriy ;

Quick, Kevin L. ;

Dugan, Laura L. .

SCIENCE, 2007, 318 (5856) :1645-1647

[5] Antidepressant effects of ketamine in depressed patients [J].

Berman, RM ;

Cappiello, A ;

Anand, A ;

Oren, DA ;

Heninger, GR ;

Charney, DS ;

Krystal, JH .

BIOLOGICAL PSYCHIATRY, 2000, 47 (04) :351-354

[6] MICHAEL ADDITIONS TO ACRYLONITRILE, METHYL ACRYLATE AND METHYL VINYL KETONE TO NB-BENZYLIDENETRYPTOPHAN METHYL-ESTER [J].

BRANA, MF ;

GARRIDO, M ;

RODRIGUEZ, MLL ;

MORCILLO, MJ .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1990, 27 (02) :357-358

[7]

BURAK K, 1985, FARMACO-ED SCI, V40, P285

[8] ASYMMETRIC SYNTHESES OF PROTECTED DERIVATIVES OF ORNITHINE- -METHANOLOGS AND ARGININE-2,3-METHANOLOGS [J].

BURGESS, K ;

HO, KK .

TETRAHEDRON LETTERS, 1992, 33 (39) :5677-5680

[9] HCN1 Channel Subunits Are a Molecular Substrate for Hypnotic Actions of Ketamine [J].

Chen, Xiangdong ;

Shu, Shaofang ;

Bayliss, Douglas A. .

JOURNAL OF NEUROSCIENCE, 2009, 29 (03) :560-569

[10] Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes [J].

Coates, KM ;

Flood, P .

BRITISH JOURNAL OF PHARMACOLOGY, 2001, 134 (04) :871-879

← 1 2 3 4 5 6 →