The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases

被引：24

作者：

Hu, LY ^{[1
]}

Boxer, PA ^{[1
]}

Kesten, SR ^{[1
]}

Lei, HSJ ^{[1
]}

Wustrow, DJ ^{[1
]}

Moreland, DW ^{[1
]}

Zhang, LM ^{[1
]}

Ahn, K ^{[1
]}

Ryder, TR ^{[1
]}

Liu, XH ^{[1
]}

Rubin, JR ^{[1
]}

Fahnoe, K ^{[1
]}

Carroll, RT ^{[1
]}

Dutta, S ^{[1
]}

Fahnoe, DC ^{[1
]}

Probert, AW ^{[1
]}

Roof, RL ^{[1
]}

Rafferty, MF ^{[1
]}

Kostlan, CR ^{[1
]}

Scholten, JD ^{[1
]}

Hood, M ^{[1
]}

Ren, XD ^{[1
]}

Schielke, GP ^{[1
]}

Su, TZ ^{[1
]}

Taylor, CP ^{[1
]}

Mistry, A ^{[1
]}

McConnell, P ^{[1
]}

Hasemann, C ^{[1
]}

Ohren, J ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Ann Arbor, MI USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 09期

关键词：

D O I：

10.1016/j.bmcl.2005.07.058

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The inhibition of the cytosolic isoenzyme BCAT that is expressed specifically in neuronal tissue is likely to be useful for the treatment of neurodegenerative and other neurological disorders where glutamatergic mechanisms are implicated. Compound 2 exhibited an IC50 of 0.8 mu M in the hBCATc assays; it is an active and selective inhibitor. Inhibitor 2 also blocked calcium influx into neuronal cells following inhibition of glutamate uptake, and demonstrated neuroprotective efficacy in vivo. SAR, pharmacology, and the crystal structure of hBCATc with inhibitor 2 are described. (C) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2337 / 2340

页数：4

共 50 条

[31] The Branched-Chain Amino Acid Aminotransferase Encoded by ilvE Is Involved in Acid Tolerance in Streptococcus mutans
Santiago, Brendaliz
MacGilvray, Matthew
Faustoferri, Roberta C.
Quivey, Robert G., Jr.
JOURNAL OF BACTERIOLOGY, 2012, 194 (08) : 2010 - 2019
[32] Regulation of branched-chain amino acid metabolism and pharmacological effects of branched-chain amino acids
Shimomura, Y
Murakami, T
Nagasaki, M
Honda, T
Goto, H
Kotake, K
Kurokawa, T
Nonami, T
HEPATOLOGY RESEARCH, 2004, 30 : S3 - S8
[33] Inhibitors of branched-chain amino acid biosynthesis as potential antituberculosis agents
Grandoni, JA
Marta, PT
Schloss, JV
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1998, 42 (04) : 475 - 482
[34] ACTIVITIES OF BRANCHED-CHAIN AMINO-ACID AMINOTRANSFERASE AND BRANCHED-CHAIN 2-OXO ACID DEHYDROGENASE COMPLEX IN TISSUES OF MATERNAL AND FETAL SHEEP
GOODWIN, GW
GIBBONEY, W
PAXTON, R
HARRIS, RA
LEMONS, JA
BIOCHEMICAL JOURNAL, 1987, 242 (01) : 305 - 308
[35] Branched-chain amino acids in liver diseases
Kazuto Tajiri
Yukihiro Shimizu
World Journal of Gastroenterology, 2013, (43) : 7620 - 7629
[36] BRANCHED-CHAIN AMINO-ACID AMINOTRANSFERASE OF ESCHERICHIA-COLI - OVERPRODUCTION AND PROPERTIES
INOUE, K
KURAMITSU, S
AKI, K
WATANABE, Y
TAKAGI, T
NISHIGAI, M
IKAI, A
KAGAMIYAMA, H
JOURNAL OF BIOCHEMISTRY, 1988, 104 (05): : 777 - 784
[37] Branched-chain amino acids in liver diseases
Tajiri, Kazuto
Shimizu, Yukihiro
WORLD JOURNAL OF GASTROENTEROLOGY, 2013, 19 (43) : 7620 - 7629
[38] Arabidopsis branched-chain aminotransferase 3 functions in both amino acid and glucosinolate biosynthesis
Knill, Tanja
Schuster, Joachim
Reichelt, Michael
Gershenzon, Jonathan
Binder, Stefan
PLANT PHYSIOLOGY, 2008, 146 (03) : 1028 - 1039
[39] BRANCHED-CHAIN AMINO-ACID AMINOTRANSFERASE FROM RUMEN CILIATE GENUS ENTODINIUM
WAKITA, M
HOSHINO, S
JOURNAL OF PROTOZOOLOGY, 1975, 22 (02): : 281 - 285
[40] Purification and cloning of the mitochondrial branched-chain amino acid aminotransferase from sheep placenta
Faure, M
Glomot, F
Bledsoe, R
Hutson, S
Papet, I
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1999, 259 (1-2): : 104 - 111

← 1 2 3 4 5 →