Pyrrolopyridazine MEK inhibitors.
The synthesis and SAR of a series of pyrrolopyridazine MEK inhibitors are reported. Optimal activity was achieved by incorporation of a 4-phenoxyaniline substituent at C4 and an acylated amine at C6.
Chen
Zhong
Z
Bristol-Myers Squibb, Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. zhong.chen@bms.com
Kim
Soong-Hoon
SH
Barbosa
Stephanie A
SA
Huynh
Tram
T
Tortolani
David R
DR
Leavitt
Kenneth J
KJ
Wei
Donna D
DD
Manne
Veeraswamy
V
Ricca
Carolyn S
CS
Gullo-Brown
Johnni
J
Poss
Michael A
MA
Vaccaro
Wayne
W
Salvati
Mark E
ME
D000215:Acylation; D000588:Amines / Q000737:chemistry; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000588:Amines; D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D011724:Pyridazines; D011758:Pyrroles; C508945:Pyrrolopyridazine; C062482:pyridazine; D020929:Mitogen-Activated Protein Kinase Kinases; C023650:aniline