1-(Arylpiperazinylamidoalkyl)-pyrimidones: orally active inhibitors of lipoprotein-associated phospholipase A(2).
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.
Bloomer
J C
JC
GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK.
Boyd
H F
HF
Hickey
D M
DM
Ife
R J
RJ
Leach
C A
CA
Macphee
C H
CH
Milliner
K J
KJ
Pinto
I L
IL
Rawlings
D A
DA
Smith
S A
SA
Stansfield
I G
IG
Stanway
S J
SJ
Taylor
M A
MA
Theobald
C J
CJ
Whittaker
C M
CM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008657:Metabolic Clearance Rate / Q000502:physiology; D008862:Microsomes, Liver / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000097:blood*; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D004791:Enzyme Inhibitors; D010879:Piperazines; D011744:Pyrimidinones; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C031503:phenylpiperazine