The development of new triazole based inhibitors of tumor necrosis factor-α (TNF-α) production

被引：46
作者：
Tullis, JS
VanRens, JC
Natchus, MG
Clark, MP
De, B
Hsieh, LC
Janusz, MJ
机构：
[1] Procter & Gamble Pharmaceut, Hlth Care Res Ctr, Mason, OH 45040 USA
[2] Array Biopharma, Boulder, CO 80301 USA
[3] Xemplar BioSci, Atlanta, GA 30309 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 10期
关键词：
D O I：
10.1016/S0960-894X(03)00238-5
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
4-Aryl-5-pyridyl and 4-aryl-5-pyrimidyl based inhibitors of TNF-alpha production, which contain a novel triazole 5-member heterocyclic core, are described. Many pyridyl triazoles containing either an alkyl ether or a substituted aryl side chain on the triazole core showed sub-micromolar activity against LPS-induced TNF-alpha, while pyrimidyl triazoles containing an ethoxymethyl side chain exhibited even better inhibitory activity. Secondary screening data are presented for the pyrimidyl triazoles. Triazole 14e combined excellent potency with good oral bioavailability in the rat. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：1665 / 1668
页数：4
相关论文
共 11 条
[1]   The effects of age structure on the labor force and retirement in China [J].
Adamchak, DJ .
SOCIAL SCIENCE JOURNAL, 2001, 38 (01) :1-11
[2]   5-(3-CARBOXYMETHOXYPHENYL)-2-(4,5-DIMETHYLTHIAZOLYL)-3-(4-SULFOPHENYL)TETRAZOLIUM, INNER SALT (MTS) AND RELATED ANALOGS OF 3-(4,5-DIMETHYLTHIAZOLYL)-2,5-DIPHENYLTETRAZOLIUM BROMIDE (MTT) REDUCING TO PURPLE WATER-SOLUBLE FORMAZANS AS CELL-VIABILITY INDICATORS [J].
BARLTROP, JA ;
OWEN, TC ;
CORY, AH ;
CORY, JG .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1991, 1 (11) :611-&
[3]   Cytokines in autoimmunity [J].
Brennan, FM ;
Feldmann, M .
CURRENT OPINION IN IMMUNOLOGY, 1996, 8 (06) :872-877
[4]   Inhibitors of p38α MAP kinase [J].
Chakravarty, S .
ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 37, 2002, 37 :177-186
[5]   2,4,5-TRIARYLIMIDAZOLE INHIBITORS OF IL-1 BIOSYNTHESIS [J].
GALLAGHER, TF ;
FIERTHOMPSON, SM ;
GARIGIPATI, RS ;
SORENSON, ME ;
SMIETANA, JM ;
LEE, D ;
BENDER, PE ;
LEE, JC ;
LAYDON, JT ;
GRISWOLD, DE ;
CHABOTFLETCHER, MC ;
BRETON, JJ ;
ADAMS, JL .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (11) :1171-1176
[6]   Mono-iodoacetate-induced experimental osteoarthritis - A dose-response study of loss of mobility, morphology, and biochemistry [J].
Guingamp, C ;
GegoutPottie, P ;
Philippe, L ;
Terlain, B ;
Netter, P ;
Gillet, P .
ARTHRITIS AND RHEUMATISM, 1997, 40 (09) :1670-1679
[7]   New aryl/heteroaryl C-N bond cross-coupling reactions via arylboronic acid cupric acetate arylation [J].
Lam, PYS ;
Clark, CG ;
Saubern, S ;
Adams, J ;
Winters, MP ;
Chan, DMT ;
Combs, A .
TETRAHEDRON LETTERS, 1998, 39 (19) :2941-2944
[8]   Ethenylation and alkynylation in palladium-catalyzed carbosubstitution in heteroazines [J].
Mangalagiu, I ;
Benneche, T ;
Undheim, K .
ACTA CHEMICA SCANDINAVICA, 1996, 50 (10) :914-917
[9]   PROTECTION AGAINST A LETHAL DOSE OF ENDOTOXIN BY AN INHIBITOR OF TUMOR-NECROSIS-FACTOR PROCESSING [J].
MOHLER, KM ;
SLEATH, PR ;
FITZNER, JN ;
CERRETTI, DP ;
ALDERSON, M ;
KERWAR, SS ;
TORRANCE, DS ;
OTTENEVANS, C ;
GREENSTREET, T ;
WEERAWARNA, K ;
KRONHEIM, SR ;
PETERSEN, M ;
GERHART, M ;
KOZLOSKY, CJ ;
MARCH, CJ ;
BLACK, RA .
NATURE, 1994, 370 (6486) :218-220
[10]   Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein [J].
Moreland, LW ;
Baumgartner, SW ;
Schiff, MH ;
Tindall, EA ;
Fleischmann, RM ;
Weaver, AL ;
Ettlinger, RE ;
Cohen, S ;
Koopman, WJ ;
Mohler, K ;
Widmer, MB ;
Blosch, CM .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (03) :141-147
12