A 13C NMR approach to categorizing potential limitations of α,β-unsaturated carbonyl systems in drug-like molecules

被引：12

作者：

Cusack, KP ^{[1
]}

Arnold, LD ^{[1
]}

Barberis, CE ^{[1
]}

Chen, HP ^{[1
]}

Ericsson, AM ^{[1
]}

Gaza-Bulseco, GS ^{[1
]}

Gordon, TD ^{[1
]}

Grinnell, CM ^{[1
]}

Harsch, A ^{[1
]}

Pellegrini, M ^{[1
]}

Tarcsa, E ^{[1
]}

机构：

[1] Abbot Biores Ctr, Worcester, MA 01605 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 22期

关键词：

Michael acceptor; electrophilicity; alpha; beta-unsaturated; NMR; physical properties;

D O I：

10.1016/j.bmcl.2004.09.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compounds that contain an alpha,beta-unsaturated carbonyl moiety are often flagged as potential Michael acceptors. All alpha,beta-unsaturated carbonyl moieties are not equivalent, however, and we sought to better understand this system and its potential implications in drug-like molecules. Measurement of the C-13 NMR shift of the beta-carbon and correlation to in vitro results allowed compounds in our collection to be categorized as potential Michael acceptors, potential substrates for NADPH, or as photoisomerizable. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：5503 / 5507

页数：5

共 21 条

[1] Mapping the kinase domain of Janus Kinase 3 [J].

Adams, C ;

Aldous, DJ ;

Amendola, S ;

Bamborough, P ;

Bright, C ;

Crowe, S ;

Eastwood, P ;

Fenton, G ;

Foster, M ;

Harrison, TKP ;

King, S ;

Lai, J ;

Lawrence, C ;

Letallec, JP ;

McCarthy, C ;

Moorcroft, N ;

Page, K ;

Rao, S ;

Redford, J ;

Sadiq, S ;

Smith, K ;

Souness, JE ;

Thurairatnam, S ;

Vine, M ;

Wyman, B .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (18) :3105-3110

[2]

Baillie TA, 2001, DRUG METAB DISPOS, V29, P1614

[3]

BASF AG, 2000, Patent No. 0075139

[4] MLEV-17-BASED TWO-DIMENSIONAL HOMONUCLEAR MAGNETIZATION TRANSFER SPECTROSCOPY [J].

BAX, A ;

DAVIS, DG .

JOURNAL OF MAGNETIC RESONANCE, 1985, 65 (02) :355-360

[5] H-1 AND C-13 ASSIGNMENTS FROM SENSITIVITY-ENHANCED DETECTION OF HETERONUCLEAR MULTIPLE-BOND CONNECTIVITY BY 2D MULTIPLE QUANTUM NMR [J].

BAX, A ;

SUMMERS, MF .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1986, 108 (08) :2093-2094

[6] PRACTICAL ASPECTS OF TWO-DIMENSIONAL TRANSVERSE NOE SPECTROSCOPY [J].

BAX, A ;

DAVIS, DG .

JOURNAL OF MAGNETIC RESONANCE, 1985, 63 (01) :207-213

[7] Role of quinones in toxicology [J].

Bolton, JL ;

Trush, MA ;

Penning, TM ;

Dryhurst, G ;

Monks, TJ .

CHEMICAL RESEARCH IN TOXICOLOGY, 2000, 13 (03) :135-160

[8]

DING J, 1994, DAXUE HUAXUE, V9, P51

[9]

Fabbro D, 2002, CURR OPIN DRUG DISC, V5, P701

[10] Strategic pooling of compounds for high-throughput screening [J].

Hann, M ;

Hudson, B ;

Lewell, X ;

Lifely, R ;

Miller, L ;

Ramsden, N .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1999, 39 (05) :897-902

← 1 2 3 →