Lp-PLA2 inhibitors GlaxoSmithKline

IDrugs

Volumn 4, Issue 10, 2001, Pages 1173-1177

  Booker, Michael L ^a  

^a GENZYME CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 30944453174     PISSN: 13697056     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (27)

1. 191080 SB 203347, an inhibitor of 14 kDa phospholipase A2, alters human neutrophil arachidonic acid release and metabolism and prolongs survival in murine endotoxin shock. Marshall LA, Hall RH, Winkler JD, Badger A, Bolognese B, Roshak A, Flamberg PL, Sung CM, Chabot Reicher M, Adams JL J PHARMACOL EXP THER 1995 274 3 12541262.
2. 243231 Eighth Symposium on Medicinal Chemistry in Eastern England University of Hertfordshire, UK. Buckle DR IDDB MEETING REPORT'1997 April 17.
3. 263095 Atherogenic LDL: Pathophysiology and New Therapeutic Approaches Satellite Symposium of the Xlth International Symposium on Atherosclerosis, Abbaye de Royaumont, France. Yla-Herttuala S IDDB MEETING REPORT W97 October2-4.
4. 278454 Novel structures as phospholipase A, (PLAJ inhibitors. EXP OPIN THER PATW9S 6 7 677-680.
5. 333565 Upoprotein-associated phospholipase A, platelet activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor. Macphee CH, Moores KE, Boyd HF, Dhanak D, Ife RJ BIOCHEM J1999 338 Pt 2 479 - 487. Discusses the role of endproducts of Lp-PLA, activity in atherosclerosis. Provides detailed data on the ability of SB-222657 to inhibit the enzyme.
6. 339220 2-(Alkylthlo)pyrimidin-4-ones: novel, reversible inhibitors of lipoproteln-associated phospholipase A,. Leach CA RSC-SCI MED CHEM SYMPOSIUM 199910:P5.
7. 370757 2-(Alkylthio)pyrlmldin-4-ones as novel, reversible inhibtors of lipoprotein-associated phospholipase A,. Boyd HF, Flynn ST, Hickey DMB, Ife RJ, Jones.M, Leach CA, Macphee CH, Milliner KJ, Rawlings DA, Slingsby BP, Smith SA, Tew DG BIOORG MED CHEM LETT2000 10 4 395-398. Provides details on the structure and efficacy of the pyrimidone class.
8. 380297 SB-253514 and analogues; novel Inhibitors of lipoproteins associated phospholipase A, produced by Pseudomonas fluorescens DSM 11579. I. Fermentation of the producing strain, isolation and biological activity. Thirkettle J, Alvarez E, Boyd H, Brown M, Diez E, Hueso J J ANTIB1OT2000 53 7 664 - 669.
9. 381305 Natural product derived Inhibitors of lipoprotein associated phospholipase A2, synthesis and activity of analogues of SB-253S14. Pinto IL, Boyd HF, Mickey DMB BIOORG MED CHEMLETT2000 10 17 2015-2017. Paper received May 2000. Lipoprotein-associated phospholipase A, (or PAF acetylhydmlase) is the enzyme that hydrolyzes PAF and oxidizes phosphatidylcholine. Its inhibition is thus a potential target in the design of novel agents for the treatment of atherosclerosis. Screening of natural products has proved a good source of lead phospholipase A2 inhibitors; SB253514 is. a relatively' simple inhibitor identified from Pseudomonas fluorescens. Exploration of the SAR of this cyclic enolcarbamate has identified simpler, more potent enzyme inhibitors.
10. 382884 Medicinal Chemistry 16th International Symposium Bologna, Italy. Alison Eyles IDDB MEETING REPORT2000 September 18-22.
11. 383631 Lipoprotein-associated PLA3 inhibition a novel, non lipid lowering strategy for atherosclerosis therapy. Leach C INT SYMP MED CHEM 200016th September 18-22 ML 14.
12. 385072 Medicinal Chemistry 16th International Symposium (Part IV) Bologna, Italy. Buckle DR IDDB MEETING REPORT2000 September 18-22.
13. 391555 N-1 substituted pyrimidin-4-ones: novel, orally active inhibitors of lipoproteln-associated phospholipase A2. Boyd HF, Fell SCM, Flynn ST, Mickey DMB, He RJ, Leach CA, Macphee CH, Milliner KJ, Moores KE, Pinto IL, Porter RA, et al BIOORG MED CHEM LETT2000 10 22 2557 - 2561. Provides details on the structure and efficacy of the pyrimidone class.
14. 399771 Product development pipeline: February 2001 GlaxoSmithKline pic COMPANY BROCHURE 2001 February 22. In the new GlaxoSmithKline pipeline, four new compounds were revealed: the PLA, inhibitor SB-435495; the NK1 receptor antagonist GW-597599; the glycine receptor antagonist GW-468816; and the dual Erb-B2/EGFR tyrosine kinase inhibitor GW-572016.
15. 399806 GSK Inaugural Investors Meeting, London - 'GSK R&D'. Yamada T COMPANY PRESENTATION 2001 February 22. Tashi Yamada, Chairman RSD GlaxoSmithKline, gave an outline of the long-, medium- and short-term R&D strategy for the company.
16. 399991 Genomic derived drug for cardiovascular disease in human trials: Human Genome Sciences' collaborator GlaxoSmithKline describes human trials of a lead compound. Human Genome Sciences Inc PRESS RELEASE2001 February 23.
17. 400047 Partners Human Genome Sciences Inc COMPANY WORLD WIDE WEB S/7H2001 February 26. A list of HGS's partnerships, including those with GlaxoSmithKline, Merck KGaA, Takeda and Sanofi-Synthélabo, among others.
18. 401355 The Identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A,. Boyd HF, Hammond B, Hickey DM, Ife RJ, Leach CA, Lewis VA, Macphee CH, Milliner KJ, Pinto IL, Smith SA, Stansfield IG, Theobald CJ, Whittaker CM BIOORG MED CHEM LETT 2001115701-704. Inhibition of lipoprotein-associated PLA, (Lp-PLAJ provides a new approach to the treatment of atherosclerosis. One such inhibitor, SB-435495 markedly reduces circulating levels of Lp-PLAf The previously described 1-[(amidolinked]-alkyl)-pyrimidones were highly lipophilic, poorly soluble and unsuitable for oral administration. This paper describes the identification of compounds with superior solubility characteristics.
19. 407419 Human Genome Sciences reports financial results for first quarter of 2001. Human Genome Sciences Inc PRESS RELEASE2W\ April 27.
20. 408528 Hydrolysis of platelet-activating factor by human serum paraoxonase. Rodrigo L, Mackness B, Durrington PN, Hemandez A, Mackness Ml BIOCHEM J2001 354 1 - 7.
21. 408529 Lipoprotein-associated phospholipase A, platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions. Hakkinen T, Luoma JS, Hiltunen MO, Macphee CH, Milliner KJ, Patel L, Rice SQ, Tew DG, Karkola K, Yla Herttuala S ARTERIOSCLER THROMB VASC BIOL 1999 19 2909 - 2917. A good discussion of the role of Lp-PLA, in atherosclerosis, focusing on the enzyme in both plasma and plaque.
22. 412547 GSK presentation at Goldman Sachs Healthcare Conference - June 13,2001. GlaxoSmithKIine pic COMPANY PRESENTATION2001 June 13. Robert Ingram, COO and President Pharmaceutical Operations and James Palmer, SVP New Product Development, GlaxoSmithKIine, gave a presentation at the Goldman Sachs 22nd Annual Healthcare Conference in California which included a discussion of the GlaxoSmithKIine R&D pipeline.
23. 416678 Llpoproteln-assoclated PLA2 inhibition - a novel, non-lipid lowering strategy for atherosclerosis therapy. Leach CA, Hickey DMB, Ife RJ, Macphee CH, Smith SA, Tew DG FARMACO2001 56 1-2 45 - 50. A good general discussion of the role of Lp-PLA2 in atherosclerosis. Also discusses inhibitory strategies and the development of the azetidinones.
24. 421405 Human Genome Sciences receives clinical milestone payment from partner. Human Genome Sciences Inc PRESS RELEASE2001 September 6.
25. 422380 Drug development update: SB-435495. GlaxoSmithKIine pic COMPANY COMMUNICATION2001 September 17. Dr Stephen Smith, researcher, GlaxoSmithKIine, confirmed that SB-435495 was one of the series of compounds from the company that contained the pyrimidin-4-one ring system. He added that a maunscript confirming the compound's structure would shortly be submitted, with possible publication anticipated before the end of 2001.
26. 424613 JP Morgan H&Q's Annual Genomics Conference - October 12, 2001. GlaxoSmithKline pic COMPANY PRESENTATION 2001 October 2. Dr Alien Roses, Senior VP, Genetics Research, GSK, presented at the JP Morgan H&Q's Annual Genomics Conference on October 2nd, in Boston, MA. He gave an overview of the pharmacogenetics and genomics programs ongoing at GSK and how such programs could impact the way new medicines are discovered and how patients may be treated in the future.
27. 422526 RSC-SCI Medicinal Chemistry - 11th Symposium (Part I), Cambridge, UK. Norman P IDDB MEETING REPORT 2001 September 9-12. Dr Stephen Smith, GlaxoSmithKline, described SAR modifications leading to the identification of SB-435495.