Mechanistic studies leading to a new procedure for rapid, microwave assisted generation of pyridine-3,5-dicarbonitrile libraries

被引：43

作者：

Guo, Kai ^{[1
]}

Thompson, Mark J. ^{[1
]}

Reddy, Tummala R. K. ^{[1
]}

Mutter, Roger ^{[1
]}

Chen, Beining ^{[1
]}

机构：

[1] Univ Sheffield, Dept Chem, Sheffield S3 7HF, S Yorkshire, England

来源：

TETRAHEDRON | 2007年 / 63卷 / 24期

关键词：

pyridine-3,5-dicarbonitriles; drug-like molecules; aerobic oxidation; mechanistic study; library synthesis; microwave assisted reactions;

D O I：

10.1016/j.tet.2007.03.139

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Mechanistic investigations into the multi-component synthesis of pyridine-3,5-dicarbonitriles have established a defined reaction pathway, particularly clarifying the role of aerobic oxidation in conversion of the intermediate 1,4-dihydropyridines into the final products. Based on such improved understanding of the reaction mechanism, optimised conditions for the preparation of compound libraries based on this core structure have been developed and represent a significant improvement in yield over existing protocols. Particularly, microwave assisted synthesis was found to provide a procedure suitable for high-throughput synthesis of pyridine-3,5-dicarbonitrile libraries. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5300 / 5311

页数：12

共 11 条

[1] New, non-adenosine, high-potency agonists for the human adenosine A2B receptor with an improved selectivity profile compared to the reference agonist n-ethylcarboxamidoadenosine [J].

Beukers, MW ;

Chang, LCW ;

Künzel, JKVD ;

Mulder-Krieger, T ;

Spanjersberg, RF ;

Brussee, J ;

Ijzerman, AP .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (15) :3707-3709

[2] A series of ligands displaying a remarkable agonistic-antagonistic profile at the adenosine A1 receptor [J].

Chang, LCW ;

Künzel, JKVF ;

Mulder-Krieger, T ;

Spanjersberg, RF ;

Roerink, SF ;

van den Hout, G ;

Beukers, MW ;

Brussee, J ;

IJzerman, AP .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (06) :2045-2053

[3]

Elghandour AHH, 1997, INDIAN J CHEM B, V36, P79

[4] One-step, three-component synthesis of pyridines and 1,4-dihydropyridines with manifold medicinal utility [J].

Evdokimov, NM ;

Magedov, IV ;

Kireev, AS ;

Kornienko, A .

ORGANIC LETTERS, 2006, 8 (05) :899-902

[5]

GUO K, 2007, EUR J MED CHEM

[6] Multi-component reactions : Emerging chemistry in drug discovery 'From xylocain to crixivan' [J].

Hulme, C ;

Gore, V .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (01) :51-80

[7]

KAMBE S, 1981, SYNTHESIS-STUTTGART, P531

[8]

KORNIENKO AA, COMMUNICATION

[9] Mimicking dominant negative inhibition of prion replication through structure-based drug design [J].

Perrier, V ;

Wallace, AC ;

Kaneko, K ;

Safar, J ;

Prusiner, SB ;

Cohen, FE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (11) :6073-6078

[10] Library design, synthesis, and screening: Pyridine dicarbonitriles as potential prion disease therapeutics [J].

Reddy, TRK ;

Mutter, R ;

Heal, W ;

Guo, K ;

Gillet, VJ ;

Pratt, S ;

Chen, B .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (02) :607-615

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