title: 3-amido-4-anilinoquinolines as CSF-1R kinase inhibitors 2: Optimization of the PK profile.
abstract: The optimization of compounds from the 3-amido-4-anilinoquinolines series of CSF-1R kinase inhibitors is described. The series has excellent activity and kinase selectivity. Excellent physical properties and rodent PK profiles were achieved through the introduction of cyclic amines at the quinoline 6-position. Compounds with good activity in a mouse PD model measuring inhibition of pCSF-1R were identified.
authors.affiliation: Cancer Research, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. david.scott@astrazeneca.com
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
authors.forename: Kirsten J
authors.initials: KJ
authors.lastname: Bell
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Campbell
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Cook
authors.forename: Les A
authors.initials: LA
authors.lastname: Dakin
authors.forename: David J
authors.initials: DJ
authors.lastname: Del Valle
authors.forename: Lisa
authors.initials: L
authors.lastname: Drew
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gero
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Hattersley
authors.forename: Charles A
authors.initials: CA
authors.lastname: Omer
authors.forename: Boris
authors.initials: B
authors.lastname: Tyurin
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; 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*
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D016186:Receptor, Macrophage Colony-Stimulating Factor