A library of novel hydroxamic acids targeting the metallo-protease family: Design, parallel synthesis and screening

被引：31

作者：

Flipo, Marion ^{[1
]}

Beghyn, Terence ^{[1
]}

Charton, Julie ^{[1
]}

Leroux, Virginie A. ^{[1
]}

Deprez, Benoit P. ^{[1
]}

Deprez-Poulain, Rebecca F. ^{[1
]}

机构：

[1] Univ Lille 2, INSERM, Inst Pasteur, U761, F-59006 Lille, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 01期

关键词：

metallo-protease inhibitors; hydroxamate; malonic; Zn2+ binding group; targeted library; chemical biology;

D O I：

10.1016/j.bmc.2006.10.010

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：

We report here the design and parallel synthesis of 217 compounds based on a malonic-hydroxamic acid template. These compounds are obtained via a two-step solution-phase procedure. The set of diverse building-blocks used makes this strategy suitable for the search of inhibitors of various metallo-proteases and for the investigation of the biological role of new metallo-proteases. As a proof of concept, we screened this library on Neutral Aminopeptidase (APN; EC 3.4.11.2), the prototypal enzyme of the M1 family. Several submicromolar inhibitors were identified. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：63 / 76

页数：14

共 36 条

[1]

Abbenante Giovanni, 2005, Med Chem, V1, P71, DOI 10.2174/1573406053402569

[2] ACE revisited: A new target for structure-based drug design [J].

Acharya, KR ;

Sturrock, ED ;

Riordan, JF ;

Ehlers, MRW .

NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (11) :891-902

[3]

Antczak C, 2001, J BIOL REG HOMEOS AG, V15, P130

[4] Synthesis and structure-activity relationship of α-sulfonylhydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis [J].

Aranapakam, V ;

Grosu, GT ;

Davis, JM ;

Hu, BH ;

Ellingboe, J ;

Baker, JL ;

Skotnicki, JS ;

Zask, A ;

DiJoseph, JF ;

Sung, A ;

Sharr, MA ;

Killar, LM ;

Walter, T ;

Jin, GX ;

Cowling, R .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (12) :2361-2375

[5] Synthesis and structure-activity relationship of N-substituted 4-arylsulfonylpiperidine-4-hydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis [J].

Aranapakam, V ;

Davis, JM ;

Grosu, GT ;

Baker, J ;

Ellingboe, J ;

Zask, A ;

Levin, JI ;

Sandanayaka, VP ;

Du, ML ;

Skotnicki, JS ;

DiJoseph, JF ;

Sung, A ;

Sharr, MA ;

Killar, LM ;

Walter, T ;

Jin, GX ;

Cowling, R ;

Tillett, J ;

Zhao, WU ;

McDevitt, J ;

Xu, ZB .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (12) :2376-2396

[6] Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects [J].

Bauvois, B ;

Dauzonne, D .

MEDICINAL RESEARCH REVIEWS, 2006, 26 (01) :88-130

[7] HYDROXAMIC ACIDS AS POTENT INHIBITORS OF ENDOTHELIN-CONVERTING ENZYME FROM HUMAN BRONCHIOLAR SMOOTH-MUSCLE [J].

BIHOVSKY, R ;

LEVINSON, BL ;

LOEWI, RC ;

ERHARDT, PW ;

POLOKOFF, MA .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (12) :2119-2129

[8] Novel hydroxamate and anilide derivatives as potent histone deacetylase inhibitors: Synthesis and antiproliferative evaluation [J].

Bouchain, G ;

Delorme, D .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (22) :2359-2372

[9]

Burns CJ, 1998, ANGEW CHEM INT EDIT, V37, P2848, DOI 10.1002/(SICI)1521-3773(19981102)37:20<2848::AID-ANIE2848>3.0.CO

[10]

2-C

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