2-Arylbenzoxazoles as novel cholesteryl ester transfer protein inhibitors: Optimization via array synthesis

被引：35

作者：

Harikrishnan, Lalgudi S. ^{[1
]}

Kamau, Muthoni G. ^{[1
]}

Herpin, Timothy F. ^{[1
]}

Morton, George C. ^{[1
]}

Liu, Yalei ^{[1
]}

Cooper, Christopher B. ^{[1
]}

Salvati, Mark E. ^{[1
]}

Qiao, Jennifer X. ^{[1
]}

Wang, Tammy C. ^{[1
]}

Adam, Leonard P. ^{[1
]}

Taylor, David S. ^{[1
]}

Chen, Alice Ye A. ^{[1
]}

Yin, Xiaohong ^{[1
]}

Seethala, Ramakrishna ^{[1
]}

Peterson, Tara L. ^{[1
]}

Nirschl, David S. ^{[1
]}

Miller, Arthur V. ^{[1
]}

Weigelt, Carolyn A. ^{[1
]}

Appiah, Kingsley K. ^{[1
]}

O'Connell, Jonathan C. ^{[1
]}

Lawrence, R. Michael ^{[1
]}

机构：

[1] Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 08期

关键词：

CETP; HDL; parallel synthesis; benzoxazole; cholesteryl ester transfer protein; CETP inhibitor; coronary heart disease; CHD; SAR;

D O I：

10.1016/j.bmcl.2008.03.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-Arylbenzoxazole 5 was identified as a hit from a fluorescence-based high-throughput screen for CETP inhibitors. The synthesis and SAR investigation employing array synthesis of the A- and B-rings are described. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2640 / 2644

页数：5

共 13 条

[1] High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions [J].

Barter, P ;

Kastelein, J ;

Nunn, A ;

Hobbs, R .

ATHEROSCLEROSIS, 2003, 168 (02) :195-211

[2] Cholesteryl ester transfer protein - A novel target for raising HDL and inhibiting atherosclerosis [J].

Barter, PJ ;

Brewer, HB ;

Chapman, MJ ;

Hennekens, CH ;

Rader, DJ ;

Tall, AR .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (02) :160-167

[3]

BISGAIER CL, 1993, J LIPID RES, V34, P1625

[4] Systematic review on the risk and benefit of different cholesterol-lowering interventions [J].

Bucher, HC ;

Griffith, LE ;

Guyatt, GH .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (02) :187-195

[5] INCIDENCE OF CORONARY HEART-DISEASE AND LIPOPROTEIN CHOLESTEROL LEVELS - THE FRAMINGHAM-STUDY [J].

CASTELLI, WP ;

GARRISON, RJ ;

WILSON, PWF ;

ABBOTT, RD ;

KALOUSDIAN, S ;

KANNEL, WB .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1986, 256 (20) :2835-2838

[6] Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of action [J].

Clark, RW ;

Ruggeri, RB ;

Cunningham, D ;

Bamberger, MJ .

JOURNAL OF LIPID RESEARCH, 2006, 47 (03) :537-552

[7] Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: An initial multidose study of torcetrapib [J].

Clark, RW ;

Sutfin, TA ;

Ruggeri, RB ;

Willauer, AT ;

Sugarman, ED ;

Magnus-Aryitey, G ;

Cosgrove, PG ;

Sand, TM ;

Wester, RT ;

Williams, JA ;

Perlman, ME ;

Bamberger, MJ .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (03) :490-497

[8] RANGE OF SERUM-CHOLESTEROL VALUES IN THE POPULATION DEVELOPING CORONARY-ARTERY DISEASE [J].

KANNEL, WB .

AMERICAN JOURNAL OF CARDIOLOGY, 1995, 76 (09) :C69-C77

[9] Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies [J].

Krishna, Rajesh ;

Anderson, Matt S. ;

Bergman, Arthur J. ;

Jin, Bo ;

Fallon, Marissa ;

Cote, Josee ;

Rosko, Kim ;

Chavez-Eng, Cynthia ;

Lutz, Ryan ;

Bloomfield, Daniel M. ;

Gutierrez, Maria ;

Doherty, James ;

Bieberdorf, Fredrick ;

Chodakewitz, Jeffrey ;

Gottesdiener, Keith M. ;

Wagner, John A. .

LANCET, 2007, 370 (9603) :1907-1914

[10] HDL as a target in the treatment of atherosclerotic cardiovascular disease [J].

Linsel-Nitschke, P ;

Tall, AR .

NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (03) :193-205

← 1 2 →