Synthesis of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]-quinoline-1,4,10(5H)-triones as NMDA glycine-site antagonists

被引：18

作者：

Brown, DG ^{[1
]}

Urbanek, RA ^{[1
]}

Bare, TM ^{[1
]}

McLaren, FM ^{[1
]}

Horchler, CL ^{[1
]}

Murphy, M ^{[1
]}

Steelman, GB ^{[1
]}

Empfield, JR ^{[1
]}

Forst, JM ^{[1
]}

Herzog, KJ ^{[1
]}

Xiao, WH ^{[1
]}

Dyroff, MC ^{[1
]}

Lee, CMC ^{[1
]}

Trivedi, S ^{[1
]}

Neilson, KL ^{[1
]}

Keith, RA ^{[1
]}

机构：

[1] AstraZeneca Pharmaceut, Wilmington, DE 19850 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(03)00750-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

Several members of the 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones (2) have been identified as being potent and selective NMDA glycine-site antagonists. Increasing size of the alkyl substituent on the alpha-carbon led to a progressive decrease in binding affinity. Some of these analogues possess improved drug-like properties such as cellular permeability, solubility and oral absorption. (C) 2003 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3553 / 3556

页数：4

相关论文

共 15 条

[1]

5-Aminomethylquinoxaline-2,3-diones. Part II: N-aryl derivatives as novel NMDA/glycine and AMPA antagonists. [J].

Auberson, YP ;

Acklin, P ;

Allgeier, H ;

Biollaz, M ;

Bischoff, S ;

Ofner, S ;

Veenstra, SJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (01) :71-74

[2]

Pyridazino[4,5-b]quinolinediones: Novel glycine/N-methyl-D-aspartate antagonists for the treatment of stroke [J].

Bare, TM .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1998, 35 (05) :1171-1186

[3]

Baron BM, 1996, J PHARMACOL EXP THER, V279, P62

[4]

BROWN DG, 2002, Patent No. 0226741

[5]

CATALYTIC ASYMMETRIC REDUCTIVE AMINATION OF KETONES VIA HIGHLY ENANTIOSELECTIVE HYDROGENATION OF THE C=N DOUBLE-BOND [J].

BURK, MJ ;

MARTINEZ, JP ;

FEASTER, JE ;

COSFORD, N .

TETRAHEDRON, 1994, 50 (15) :4399-4428

[6]

IVERSEN LL, 1994, NMDA RECEPTOR, P469

[7]

THE GLYCINE SITE ON THE NMDA RECEPTOR - STRUCTURE-ACTIVITY-RELATIONSHIPS AND THERAPEUTIC POTENTIAL [J].

LEESON, PD ;

IVERSEN, LL .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (24) :4053-4067

[8]

CHEMICALLY-DIVERSE LIGANDS AT THE GLYCINE-B SITE COUPLED TO N-METHYL-D-ASPARTATE (NMDA) RECEPTORS SELECTIVELY BLOCK THE LATE-PHASE OF FORMALIN-INDUCED PAIN IN MICE [J].

MILLAN, MJ ;

SEGUIN, L .

NEUROSCIENCE LETTERS, 1994, 178 (01) :139-143

[9]

GV196771A, an NMDA receptor/glycine site antagonist, attenuates mechanical allodynia in neuropathic rats and reduces tolerance induced by morphine in mice [J].

Quartaroli, M ;

Fasdelli, N ;

Bettelini, L ;

Maraia, G ;

Corsi, M .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 430 (2-3) :219-227

[10]

Effect of plasma protein binding on in vivo activity and brain penetration of glycine/NMDA receptor antagonists [J].

Rowley, M ;

Kulagowski, JJ ;

Watt, AP ;

Rathbone, D ;

Stevenson, GI ;

Carling, RW ;

Baker, R ;

Marshall, GR ;

Kemp, JA ;

Foster, AC ;

Grimwood, S ;

Hargreaves, R ;

Hurley, C ;

Saywell, KL ;

Tricklebank, MD ;

Leeson, PD .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (25) :4053-4068