N6-Cycloalkyl-2-substituted adenosine derivatives as selective, high affinity adenosine A1 receptor agonists

被引：22

作者：

Elzein, Elfatih

Kalla, Rao

Li, Xiaofen

Perry, Thao

Marquart, Tim

Micklatcher, Mark

Li, Yuan

Wu, Yuzhi

Zeng, Dewan

Zablocki, Jeff

机构：

[1] CV Therapeut Inc, Dept Bioorgan Chem, Palo Alto, CA 94304 USA

[2] CV Therapeut Inc, Dept Drug Res & Pharmacol Sci, Palo Alto, CA 94304 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 01期

关键词：

A(1)-adenosine receptors;

D O I：

10.1016/j.bmcl.2006.09.065

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of new selective, high affinity A(1)-AdoR agonists is reported. Compound 23 that incorporated a carboxylic acid functionality in the 4-position of the pyrazole ring displayed K-iL value of 1 nM for the A(1)-AdoR and > 5000-fold selectivity over the A(3) and A(2A)-AdoRs. In addition, compound 19 that incorporated a carboxamide functionality in the 4-position of the pyrazole ring displayed subnanomolar affinity for the A(1)-AdoR (K-iL = 0.6 nM) and > 600-fold selectivity over the A(3) and A(2A)-AdoRs. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：161 / 166

页数：6

共 20 条

[1] ARVINDER KD, 2003, CURR TOP MED CHEM, V3, P369
[2] NEW COPPER CHEMISTRY .3. NEW PREPARATIONS OF ETHYL 3,3-DIETHOXYPROPIONATE AND (ETHOXYCARBONYL)MALONDIALDEHYDE - CU(I)-CATALYZED ACETAL FORMATION FROM A CONJUGATED TRIPLE BOND
BERTZ, SH
DABBAGH, G
COTTE, P
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1982, 47 (11) : 2216 - 2217
[3] N6-cyclopentyl-2-(3-phenylaminocarbonyltriazene-1-yl)adenosine (TCPA), a very selective agonist with high affinity for the human adenosine A1 receptor
Beukers, MW
Wanner, MJ
Künzel, JKV
Klaasse, EC
IJzerman, AP
Koomen, GJ
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (08) : 1492 - 1503
[4] STRUCTURE-ACTIVITY-RELATIONSHIPS FOR N6-SUBSTITUTED ADENOSINES AT A BRAIN ADENOSINE-A1-RECEPTOR WITH A COMPARISON TO AN ADENOSINE-A2 RECEPTOR REGULATING CORONARY BLOOD-FLOW
DALY, JW
PADGETT, W
THOMPSON, RD
KUSACHI, S
BUGNI, WJ
OLSSON, RA
[J]. BIOCHEMICAL PHARMACOLOGY, 1986, 35 (15) : 2467 - 2481
[5] NECA-INDUCED HYPOMOTILITY IN MICE - EVIDENCE FOR A PREDOMINANTLY CENTRAL SITE OF ACTION
DURCAN, MJ
MORGAN, PF
[J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1989, 32 (02) : 487 - 490
[6] 2-pyrazolyl-N6-substituted adenosine derivatives as high affinity and selective adenosine A3 receptor agonists
Elzein, E
Palle, V
Wu, YZ
Maa, TN
Zeng, DW
Zablocki, J
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (19) : 4766 - 4773
[7] Facile preparation of nucleoside-5′-carboxylic acids
Epp, JB
Widlanski, TS
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (01) : 293 - 295
[8] Structure and function of adenosine receptors and their genes
Fredholm, BB
Arslan, G
Halldner, L
Kull, B
Schulte, G
Wasserman, W
[J]. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2000, 362 (4-5) : 364 - 374
[9] N6-substituted adenosine derivatives:: selectivity, efficacy, and species differences at A3 adenosine receptors
Gao, ZG
Blaustein, JB
Gross, AS
Melman, N
Jacobson, KA
[J]. BIOCHEMICAL PHARMACOLOGY, 2003, 65 (10) : 1675 - 1684
[10] FUNCTIONALIZED CONGENERS OF ADENOSINE - PREPARATION OF ANALOGS WITH HIGH-AFFINITY FOR A1-ADENOSINE RECEPTORS
JACOBSON, KA
KIRK, KL
PADGETT, WL
DALY, JW
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (09) : 1341 - 1346

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