2-Amino-5-benzoyl-4-phenylthiazoles: Development of potent and selective adenosine A1 receptor antagonists

被引：32

作者：

Scheiff, Anja B. ^{[1
]}

Yerande, Swapnil G. ^{[2
]}

El-Tayeb, Ali ^{[1
]}

Li, Wenjin ^{[1
]}

Inamdar, Gajanan S. ^{[2
]}

Vasu, Kamala K. ^{[2
]}

Sudarsanam, Vasudevan ^{[2
]}

Mueller, Christa E. ^{[1
]}

机构：

[1] Univ Bonn, PharmaCtr Bonn, Inst Pharmaceut, D-53121 Bonn, Germany

[2] BV Patel Pharmaceut Educ & Res Dev Ctr, Dept Med Chem, Ahmadabad 380054, Gujarat, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 06期

关键词：

Thiazole; Adenosine receptor; Adenosine A(1) receptor antagonist; Structure-activity relationships; BEARING POLAR SUBSTITUENTS; DERIVATIVES; HEART; PHARMACOLOGY; AFFINITY; AGONISTS; PRODRUG; ANALOGS; BRAIN; FK838;

D O I：

10.1016/j.bmc.2010.01.072

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：

A series of 2-amino-5-benzoyl-4-phenylthiazole derivatives was investigated in radioligand binding studies at adenosine receptor (AdoR) subtypes with the goal to obtain potent and A(1)-selective antagonists. Acylation of the 2-amino group was found to be crucial for high A(1) affinity. The best compound of the present series was 2-benzoylamino-5-p-methylbenzoyl-4-phenylthiazole (16m) showing a K-i value of 4.83 nM at rat and 57.4 nM at human A(1) receptors combined with high selectivity versus the other AdoR subtypes. The compound behaved as an antagonist in GTP shift assays at A(1) receptors. Compound 16m may serve as a new lead structure for the development of second-generation non-xanthine-derived A(1) antagonists which have potential as novel drugs. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2195 / 2203

页数：9

共 50 条

[1] Discovery of 6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)pyridazinebutanoic acid (FK838):: A novel non-xanthine adenosine A1 receptor antagonist with potent diuretic activity [J].

Akahane, A ;

Katayama, H ;

Mitsunaga, T ;

Kato, T ;

Kinoshita, T ;

Kita, Y ;

Kusunoki, T ;

Terai, T ;

Yoshida, K ;

Shiokawa, Y .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (05) :779-783

[2]

Belardinelli L, 1995, J PHARMACOL EXP THER, V275, P1167

[3] 1-Alkyl-8-(piperazine-1-sulfonyl)phenylxanthines: Development and Characterization of Adenosine A2B Receptor Antagonists and a New Radioligand with Subnanomolar Affinity and Subtype Specificity [J].

Borrmann, Thomas ;

Hinz, Sonja ;

Lertarelli, Daniela C. G. ;

Li, Wenjin ;

Florin, Nicole C. ;

Scheiff, Anja B. ;

Mueller, Christa E. .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (13) :3994-4006

[4] Adenosine receptors and asthma [J].

Brown, R. A. ;

Spina, D. ;

Page, C. P. .

BRITISH JOURNAL OF PHARMACOLOGY, 2008, 153 :S446-S456

[5] Synthesis and pharmacology of pyrido[2,3-d]pyrimidinediones bearing polar substituents as adenosine receptor antagonists [J].

Bulicz, J ;

Bertarelli, DCG ;

Baumert, D ;

Fülle, F ;

Müller, CE ;

Heber, D .

BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (08) :2837-2849

[6] New substituted 9-alkylpurines as adenosine receptor ligands [J].

Camaioni, E ;

Costanzi, S ;

Vittori, S ;

Volpini, R ;

Klotz, KN ;

Cristalli, G .

BIOORGANIC & MEDICINAL CHEMISTRY, 1998, 6 (05) :523-533

[7] Synthesis of 2-amino-5-benzoyl-4-(2-furyl)thiazoles as adenosine A2A receptor antagonists [J].

Cole, Andrew G. ;

Stauffer, Tara M. ;

Rokosz, Laura L. ;

Metzger, Axel ;

Dillard, Lawrence W. ;

Zeng, Wenguang ;

Henderson, Ian .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (02) :378-381

[8] 2-ALKYNYL DERIVATIVES OF ADENOSINE AND ADENOSINE-5'-N-ETHYLURONAMIDE AS SELECTIVE AGONISTS AT A2 ADENOSINE RECEPTORS [J].

CRISTALLI, G ;

ELEUTERI, A ;

VITTORI, S ;

VOLPINI, R ;

LOHSE, MJ ;

KLOTZ, KN .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (13) :2363-2368

[9] Caffeine analogs: biomedical impact [J].

Daly, J. W. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2007, 64 (16) :2153-2169

[10]

DIEKMANN M, 2003, THESIS U BONN GERMAN

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