Design and synthesis of novel imidazo[1,2-a]quinoxalines as PDE4 inhibitors

被引：31

作者：

Deleuze-Masquéfa, C

Gerebtzoff, G

Subra, G

Fabreguettes, JR

Ovens, A

Carraz, M

Strub, MP

Bompart, J

George, P

Bonnet, PA

机构：

[1] Fac Pharm Montpellier, Lab Chim Organ Pharmaceut, F-34093 Montpellier 5, France

[2] Fac Pharm Montpellier, Ctr Biochim Struct, F-34093 Montpellier 5, France

[3] Sanofi Synthelabo Rech, Dept Rech Syst Nerveux Cent, F-92220 Bagneux, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 05期

关键词：

phosphodiesterase; 4; imidazo[1,2-a]quinoxaline; phosphodiesterase inhibition;

D O I：

10.1016/j.bmc.2003.11.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

New imidazo[1,2-a]quinoxaline derivatives have been synthesised by condensation of an appropriate alpha-aminoalcohol with a quinoxaline followed by intramolecular cyclisation and nucleophilic substitutions. Their phosphodiesterase inhibitory activities have been assessed on a preparation of the PDE4 isoform purified from a human alveolar epithelial cell line (A549). These studies showed potent inhibitory properties that emphasize the importance of a methyl amino group at position 4 and a weakly hindered group at position 1. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1129 / 1139

页数：11

共 17 条

[1] Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory drugs
Burnouf, C
Pruniaux, MP
[J]. CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (14) : 1255 - 1296
[2] Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling
Conti, M
Richter, W
Mehats, C
Livera, G
Park, JY
Jin, C
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (08) : 5493 - 5496
[3] Phosphodiesterase 4 inhibitors, structurally unrelated to Rolipram, as promising agents for the treatment of asthma and other pathologies
Dal Piaz, V
Giovannoni, MP
[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2000, 35 (05) : 463 - 480
[4] Cyclic nucleotide phosphodiesterase in human bronchial epithelial cells: Characterization of isoenzymes and functional effects of PDE inhibitors
Dent, G
White, SR
Tenor, H
Bodtke, K
Schudt, C
Leff, AR
Magnussen, H
Rabe, KF
[J]. PULMONARY PHARMACOLOGY & THERAPEUTICS, 1998, 11 (01) : 47 - 56
[5] Houslay MD, 2003, BIOCHEM J, V370, P1, DOI 10.1042/bj20021698
[6] CONFORMATIONAL TRANSITION ACCOMPANYING BINDING OF CA-2+ TO PROTEIN ACTIVATOR OF 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE PHOSPHODIESTERASE
KLEE, CB
[J]. BIOCHEMISTRY, 1977, 16 (05) : 1017 - 1024
[7] PIPERAZINYLIMIDAZO[1,2-A]PYRAZINES WITH SELECTIVE AFFINITY FOR INVITRO ALPHA-ADRENERGIC RECEPTOR SUBTYPES
LUMMA, WC
RANDALL, WC
CRESSON, EL
HUFF, JR
HARTMAN, RD
LYON, TF
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1983, 26 (03) : 357 - 363
[8] Cyclic nucleotide phosphodiesterases and their role in endocrine cell signaling
Mehats, C
Andersen, CB
Filopanti, M
Jin, SLC
Conti, M
[J]. TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2002, 13 (01) : 29 - 35
[9] SYNTHESIS AND HYPOGLYCEMIC ACTIVITY OF SUBSTITUTED 8-(1-PIPERAZINYL)IMIDAZO[1,2-A]PYRAZINES
MEURER, LC
TOLMAN, RL
CHAPIN, EW
SAPERSTEIN, R
VICARIO, PP
ZRADA, MM
MACCOSS, M
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (21) : 3845 - 3857
[10] Imidazo[1,2-a]quinoxalines:: synthesis and cyclic nucleotide phosphodiesterase inhibitory activity
Parra, S
Laurent, F
Subra, G
Deleuze-Masquefa, C
Benezech, V
Fabreguettes, JR
Vidal, JP
Pocock, T
Elliott, K
Small, R
Escale, R
Michel, A
Chapat, JP
Bonnet, PA
[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (03) : 255 - 264

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