title: Design and synthesis of 1,5-diarylbenzimidazoles as inhibitors of the VEGF-receptor KDR.
abstract: 1,5-Diarylbenzimidazoles have been identified as potent inhibitors of KDR kinase activity. The series was developed with a goal of finding compounds with optimal drug-like properties. This communication describes structural modifications in the series that enhance solubility, lower protein binding, and provide compounds with excellent potency and pharmacokinetic profiles.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. mark_bilodeau@merck.com
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bilodeau
authors.forename: April M
authors.initials: AM
authors.lastname: Cunningham
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Koester
authors.forename: Patrice A
authors.initials: PA
authors.lastname: Ciecko
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Coll
authors.forename: William R
authors.initials: WR
authors.lastname: Huckle
authors.forename: Randall W
authors.initials: RW
authors.lastname: Hungate
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kendall
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: McFall
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Mao
authors.forename: Ruth Z
authors.initials: RZ
authors.lastname: Rutledge
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004285:Dogs; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008968:Molecular Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D040301:Vascular Endothelial Growth Factor Receptor-2