Synthesis and biological evaluation of trisubstituted imidazole derivatives as inhibitors of p38alpha mitogen-activated protein kinase.
A series of trisubstituted imidazole derivatives containing a 4-fluorophenyl group, a pyrimidine ring, and a CN- or CONH(2)-substituted benzyl moiety have been synthesized and evaluated for p38alpha MAP kinase inhibitory activity. Among them, compounds 22c, 27b, and 28b inhibited p38alpha MAP kinase with IC(50) values 27.6, 28, and 31 nM, respectively.
College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea. dkkim@ewha.ac.kr
Dae-Kee
DK
Kim
Jin-Hwi
JH
Lim
Jung A
JA
Lee
Purushottam M
PM
Dewang
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System; D008956:Models, Chemical; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011994:Recombinant Proteins; D048051:p38 Mitogen-Activated Protein Kinases