S-aryl cysteine S,S-dioxides as inhibitors of mammalian kynureninase

被引:20
作者
Drysdale, MJ
Reinhard, JF
机构
[1] Glaxo Wellcome Res & Dev Ltd, Combinatorial Med Chem, Stevenage SG1 2NY, Herts, England
[2] Glaxo Wellcome Inc, Res & Dev, Dept Pharmacol, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.1016/S0960-894X(97)10209-8
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of 2-amino-S-aryl cysteine S,S-dioxides have been synthesised and shown to inhibit kynureninase an important enzyme in the biosynthesis of the known excitotoxic moiety quinolinic acid. The most potent of these, 2-amino-5-methyl-S-phenyl cysteine S,S-dioxide 6d, inhibits interferon-gamma induced synthesis of quinolinic acid in human macrophages. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:133 / 138
页数:6
相关论文
共 17 条
[1]   QUINOLINIC ACID ACCUMULATION AND FUNCTIONAL DEFICITS FOLLOWING EXPERIMENTAL SPINAL-CORD INJURY [J].
BLIGHT, AR ;
COHEN, TI ;
SAITO, K ;
HEYES, MP .
BRAIN, 1995, 118 :735-752
[2]  
CHIARUGI A, 1995, J NEUROCHEM, V65, P1176
[3]   S-ARYL-L-CYSTEINE S,S-DIOXIDES - DESIGN, SYNTHESIS, AND EVALUATION OF A NEW CLASS OF INHIBITORS OF KYNURENINASE [J].
DUA, RK ;
TAYLOR, EW ;
PHILLIPS, RS .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (04) :1264-1270
[4]   QUINOLINIC ACID IN CEREBROSPINAL-FLUID AND SERUM IN HIV-1 INFECTION - RELATIONSHIP TO CLINICAL AND NEUROLOGICAL STATUS [J].
HEYES, MP ;
BREW, BJ ;
MARTIN, A ;
PRICE, RW ;
SALAZAR, AM ;
SIDTIS, JJ ;
YERGEY, JA ;
MOURADIAN, MM ;
SADLER, AE ;
KEILP, J ;
RUBINOW, D ;
MARKEY, SP .
ANNALS OF NEUROLOGY, 1991, 29 (02) :202-209
[5]   QUINOLINIC ACID AND KYNURENINE PATHWAY METABOLISM IN INFLAMMATORY AND NONINFLAMMATORY NEUROLOGICAL DISEASE [J].
HEYES, MP ;
SAITO, K ;
CROWLEY, JS ;
DAVIS, LE ;
DEMITRACK, MA ;
DER, M ;
DILLING, LA ;
ELIA, J ;
KRUESI, MJP ;
LACKNER, A ;
LARSEN, SA ;
LEE, K ;
LEONARD, HL ;
MARKEY, SP ;
MARTIN, A ;
MILSTEIN, S ;
MOURADIAN, MM ;
PRANZATELLI, MR ;
QUEARRY, BJ ;
SALAZAR, A ;
SMITH, M ;
STRAUSS, SE ;
SUNDERLAND, T ;
SWEDO, SW ;
TOURTELLOTTE, WW .
BRAIN, 1992, 115 :1249-1273
[6]   QUANTIFICATION OF QUINOLINIC ACID IN RAT-BRAIN, WHOLE-BLOOD, AND PLASMA BY GAS-CHROMATOGRAPHY AND NEGATIVE CHEMICAL IONIZATION MASS-SPECTROMETRY - EFFECTS OF SYSTEMIC L-TRYPTOPHAN ADMINISTRATION ON BRAIN AND BLOOD QUINOLINIC ACID CONCENTRATIONS [J].
HEYES, MP ;
MARKEY, SP .
ANALYTICAL BIOCHEMISTRY, 1988, 174 (01) :349-359
[7]   HUMAN MACROPHAGES CONVERT L-TRYPTOPHAN INTO THE NEUROTOXIN QUINOLINIC ACID [J].
HEYES, MP ;
SAITO, K ;
MARKEY, SP .
BIOCHEMICAL JOURNAL, 1992, 283 :633-635
[8]  
MARTIN A, 1992, J NEUROPSYCH CLIN N, V4, P270
[9]   SYNTHESIS AND ACTIVITY OF ENANTIOPURE (S)(M-NITROBENZOYL) ALANINE, POTENT KYNURENINE-3-HYDROXYLASE INHIBITOR [J].
NATALINI, B ;
MATTOLI, L ;
PELLICCIARI, R ;
CARPENEDO, R ;
CHIARUGI, A ;
MORONI, F .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (14) :1451-1454
[10]   The regulation of quinolinic acid in human immunodeficiency virus-infected monocytes [J].
Nottet, HSLM ;
Flanagan, EM ;
Flanagan, CR ;
Gelbard, HA ;
Gendelman, HE ;
Reinhard, JF .
JOURNAL OF NEUROVIROLOGY, 1996, 2 (02) :111-117