1-(Arylpiperazinylamidoalkyl)-pyrimidones:: Orally active inhibitors of lipoprotein-associated phospholipase A2

被引：12

作者：

Bloomer, JC ^{[1
]}

Boyd, HF ^{[1
]}

Hickey, DMB ^{[1
]}

Ife, RJ ^{[1
]}

Leach, CA ^{[1
]}

Macphee, CH ^{[1
]}

Milliner, KJ ^{[1
]}

Pinto, IL ^{[1
]}

Rawlings, DA ^{[1
]}

Smith, SA ^{[1
]}

Stansfield, IG ^{[1
]}

Stanway, SJ ^{[1
]}

Taylor, MA ^{[1
]}

Theobald, CJ ^{[1
]}

Whittaker, CM ^{[1
]}

机构：

[1] GlaxoSmithKline, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 14期

关键词：

D O I：

10.1016/S0960-894X(01)00346-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The lipophilic 1-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, inhibitors of recombinant lipoprotein-associated phospholipase A(2), has been modified to give inhibitors of high potency in human plasma and enhanced physicochemical properties. Phenylpiperazineacetamide derivative 23 shows very promising oral activity. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：1925 / 1929

页数：5

相关论文

共 6 条

[1] N-1 substituted pyrimidin-4-ones:: Novel, orally active inhibitors of lipoprotein-associated phospholipase A2 [J].

Boyd, HF ;

Fell, SCM ;

Flynn, ST ;

Hickey, DMB ;

Ife, RJ ;

Leach, CA ;

Macphee, CH ;

Milliner, KJ ;

Moores, KE ;

Pinto, IL ;

Porter, RA ;

Rawlings, DA ;

Smith, SA ;

Stansfield, IG ;

Tew, DG ;

Theobald, CJ ;

Whittaker, CM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (22) :2557-2561

[2] The identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A2 [J].

Boyd, HF ;

Hammond, B ;

Hickey, DMB ;

Ife, RJ ;

Leach, CA ;

Lewis, VA ;

Macphee, CH ;

Milliner, KJ ;

Pinto, IL ;

Smith, SA ;

Stansfield, IG ;

Theobald, CJ ;

Whittaker, CM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (05) :701-704

[3] Current and future treatment of hyperlipidemia: The role of statins [J].

Farnier, M ;

Davignon, J .

AMERICAN JOURNAL OF CARDIOLOGY, 1998, 82 (4B) :3J-10J

[4]

Macphee Colin H., 2001, Current Opinion in Pharmacology, V1, P121, DOI 10.1016/S1471-4892(01)00024-8

[5] Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. [J].

Packard, CJ ;

O'Reilly, DSJ ;

Caslake, MJ ;

McMahon, AD ;

Ford, I ;

Cooney, J ;

Macphee, CH ;

Suckling, KE ;

Krishna, M ;

Wilkinson, FE ;

Rumley, A ;

Lowe, GDO .

NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (16) :1148-1155

[6] Purification, properties, sequencing, and cloning of a lipoprotein-associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins [J].

Tew, DG ;

Southan, C ;

Rice, SQJ ;

Lawrence, GMP ;

Li, HD ;

Boyd, HF ;

Moores, K ;

Gloger, IS ;

Macphee, CH .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (04) :591-599