2-(alkylthio)pyrimidin-4-ones as novel, reversible inhibitors of lipoprotein-associated phospholipase A2

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 4, 2000, Pages 395-398

  Boyd, Helen F ^a   Flynn, Sean T ^a   Hickey, Deirdre M B ^a   Ife, Robert J ^a   Jones, Martin ^a   Leach, Colin A ^a   Macphee, Colin H ^a   Milliner, Kevin J ^a   Rawlings, D Anthony ^a   Slingsby, Brian P ^a   Smith, Stephen A ^a   Stansfield, Ian G ^a   Tew, David G ^a   Theobald, Colin J ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PHOSPHOLIPASE A2; PHOSPHOLIPASE A2 INHIBITOR;

ARTICLE; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; ENZYME INHIBITION; HUMAN; IC 50; STRUCTURE ACTIVITY RELATION;

DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; PHOSPHOLIPASES A; PYRIMIDINONES; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 18144439390     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00002-0     Document Type: Article

References (10)

1. The enzyme is also known as PAF acetyl hydrolase, though it is clear that the enzyme has much broader substrate specificity than this name implies. See Tew, D. G.; Southan, C.; Rice, S. Q. J.; Lawrence, M. P.; Haodong, L.; Boyd, H. F.; Moores, K.; Gloger, I. S.; Macphee, C. H. Atheroscler. Thromb. Vasc. Biol. 1996, 16 (4), 591. 3-Dimensional structural information on this enzyme is not available. Recently, the structure of a potentially related bacterial enzyme has been published: Wei, Y.; Swenson, L.; Castro, C.; Derewenda, U.; Minor, W.; Arai, H.; Aoki, J.; Inoue, K.; Servin-Gonzalez, L.; Derewenda, Z. S. Structure 1998, 6 (4), 511
2. The enzyme is also known as PAF acetyl hydrolase, though it is clear that the enzyme has much broader substrate specificity than this name implies. See Tew, D. G.; Southan, C.; Rice, S. Q. J.; Lawrence, M. P.; Haodong, L.; Boyd, H. F.; Moores, K.; Gloger, I. S.; Macphee, C. H. Atheroscler. Thromb. Vasc. Biol. 1996, 16 (4), 591. 3-Dimensional structural information on this enzyme is not available. Recently, the structure of a potentially related bacterial enzyme has been published: Wei, Y.; Swenson, L.; Castro, C.; Derewenda, U.; Minor, W.; Arai, H.; Aoki, J.; Inoue, K.; Servin-Gonzalez, L.; Derewenda, Z. S. Structure 1998, 6 (4), 511
3. Macphee C.H., Moores K.E., Boyd H.F., Dhanak D., Ife R.J., Leach C.A., Leakes D.S., Milliner K.J., Patterson R.A., Suckling K.E., Tew D.G., Hickey D.M.B. Biochem. J. 338:1999;479. and references therein.
4. Tew D.G., Boyd H.F., Ashman S., Theobald C.J., Leach C.A. Biochemistry. 37:1998;10087.
5. Brown T.H., Blakemore R.C., Blurton P., Durant G.J., Ganellin C.R., Parsons M.E., Rasmussen A.C., Rawlings D.A., Walker T.F. Eur. J. Med. Chem. 24:1989;65.
6. Orr G.F., Musso D.L. Syn. Commun. 26(1):1996;179. and references therein.
7. 50 equation using Grafit (Erithacus Software).
8. Boyd, H. F.; Hickey, D. M. B.; Ife, R. J.; Leach, C. A.; Macphee, C. H.; Tew, D. G. unpublished results.
9. 2S requires 456.
10. Rice S.Q.J., Southan C., Boyd H.F., Terrett J.A., Macphee C.H., Moores K., Tew D.G. Biochem. J. 330:1998;1309.