Synthesis and Biological Evaluation of a New Series of 2-{[4-(3,4-Dichlorophenyl)-1,2,3-thiadiazol-5-yl]sulfanyl}acetanilides as HIV-1 Inhibitors

被引：28

作者：

Zhan, Peng ^{[1
]}

Liu, Xin-Yong ^{[1
]}

Li, Zhen-Yu ^{[1
]}

Fang, Zeng-Jun ^{[1
]}

Pannecouque, Christophe ^{[2
]}

De Clereq, Erik ^{[2
]}

机构：

[1] Shandong Univ, Sch Pharmaceut Sci, Inst Med Chem, Jinan 250012, Peoples R China

[2] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

来源：

CHEMISTRY & BIODIVERSITY | 2010年 / 7卷 / 07期

关键词：

REVERSE-TRANSCRIPTASE INHIBITORS; POTENT NONNUCLEOSIDE INHIBITORS; COLORIMETRIC ASSAY; DESIGN; NNRTIS; THIOACETANILIDES; CHEMOTHERAPY; FUTURE; MUTANT; DRUGS;

D O I：

10.1002/cbdv.200900197

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：

As part of our studies to discover new HIV-1 reverse transcriptase inhibitors, a series of 3,4-dichlorophenyl substituted 1,2,3-thiadiazole thioacetanilide (TTA = [ (1,2,3-thiadiazole-5-yl)sulfanyl acet anilide) derivatives were synthesized, and in vitro anti-HIV activity was evaluated. The results revealed that nearly half of the compounds show moderate-to-good inhibitory potency against HIV-1. In particular, compound 7f is highly potent, with an EC50 value of 0.95+/-0.33 mu M. The preliminary structure - activity relationship among the newly synthesized congeners is discussed.

引用

页码：1717 / 1727

页数：11

共 26 条

[11] ON ACYLHYDRAZONES AND 1,2,3-THIADIAZOLES [J].

HURD, CD ;

MORI, RI .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1955, 77 (20) :5359-5364

[12] Design, Synthesis and Anti-HIV-1 Evaluation of Novel Arylazolylthioacetanilides as Potent NNRTIS [J].

Liu, Xinyong ;

Zhan, Peng ;

Pannecouque, Christophe ;

De Clercq, Erik .

ANTIVIRAL RESEARCH, 2009, 82 (02) :A44-A45

[13] Halogen Bonding-A Novel Interaction for Rational Drug Design? [J].

Lu, Yunxiang ;

Shi, Ting ;

Wang, Yong ;

Yang, Huaiyu ;

Yan, Xiuhua ;

Luo, Xiaoming ;

Jiang, Hualiang ;

Zhu, Weiliang .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (09) :2854-2862

[14]

MIYOSHI I, 1982, GANN MONOGR, V28, P219

[15] Tetrazole thioacetanilides: Potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant [J].

Muraglia, E ;

Kinzel, OD ;

Laufer, R ;

Miller, MD ;

Moyer, G ;

Munshi, V ;

Orvieto, F ;

Palumbi, MC ;

Pescatore, G ;

Rowley, M ;

Williarns, PD ;

Summa, V .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (10) :2748-2752

[16] Scaffold hopping in the rational design of novel HIV-1 non-nucleoside reverse transcriptase inhibitors [J].

O'Meara, Jeff A. ;

Jakalian, Araz ;

LaPlante, Steven ;

Bonneau, Pierre R. ;

Coulombe, Rene ;

Faucher, Anne-Marie ;

Guse, Ingrid ;

Landry, Serge ;

Racine, Jennifer ;

Simoneau, Bruno ;

Thavonekham, Bounkham ;

Yoakim, Christiane .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (12) :3362-3366

[17] Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors: revisited 20 years later [J].

Pannecouque, Christophe ;

Daelemans, Dirk ;

De Clercq, Erik .

NATURE PROTOCOLS, 2008, 3 (03) :427-434

[18] RAPID AND AUTOMATED TETRAZOLIUM-BASED COLORIMETRIC ASSAY FOR THE DETECTION OF ANTI-HIV COMPOUNDS [J].

PAUWELS, R ;

BALZARINI, J ;

BABA, M ;

SNOECK, R ;

SCHOLS, D ;

HERDEWIJN, P ;

DESMYTER, J ;

DECLERCQ, E .

JOURNAL OF VIROLOGICAL METHODS, 1988, 20 (04) :309-321

[19] DETECTION, ISOLATION, AND CONTINUOUS PRODUCTION OF CYTOPATHIC RETROVIRUSES (HTLV-III) FROM PATIENTS WITH AIDS AND PRE-AIDS [J].

POPOVIC, M ;

SARNGADHARAN, MG ;

READ, E ;

GALLO, RC .

SCIENCE, 1984, 224 (4648) :497-500

[20] SYNTHESIS AND PLATELET-AGGREGATION INHIBITORY ACTIVITY OF 4,5-BIS(SUBSTITUTED)-1,2,3-THIADIAZOLES [J].

THOMAS, EW ;

NISHIZAWA, EE ;

ZIMMERMANN, DC ;

WILLIAMS, DJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (04) :442-446

← 1 2 3 →