Modification of the pyrimidone 5-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, lipophilic inhibitors of lipoprotein-associated phospholipase A2, has given inhibitors of nanomolar potency and improved physicochemical properties. Compound 23 was identified as a potent, highly water soluble. CNS penetrant inhibitor suitable for intravenous administration.
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 (2001) The identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A2 Bioorganic & Medicinal Chemistry Lett11: 701-4
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 (2001) Bioorganic & Medicinal Chemistry Lett11: 701-4