Identification of 3-amido-4-anilinoquinolines as potent and selective inhibitors of CSF-1R kinase.
3-amido-4-anilinoquinolines are potent and highly selective inhibitors of CSF-1R. Their synthesis and SAR is reported, along with initial efforts to optimize the physical properties and PK through modifications at the quinoline 6- and 7-positions.
Scott
David A
DA
Cancer Research, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. david.scott@astrazeneca.com
Balliet
Carrie L
CL
Cook
Donald J
DJ
Davies
Audrey M
AM
Gero
Thomas W
TW
Omer
Charles A
CA
Poondru
Srinivasu
S
Theoclitou
Maria-Elena
ME
Tyurin
Boris
B
Zinda
Michael J
MJ
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D016186:Receptor, Macrophage Colony-Stimulating Factor