title: Methanesulfonamido-cyclohexylamine derivatives of 2,4-diaminopyrimidine as potent ALK inhibitors.
abstract: The incorporation of R,R-1,2-diaminocyclohexane at C4 in a series of 2,4-diaminopyrimidines led to a number of ALK inhibitors in which optimized activity was achieved by conversion of the 2-amino group into a methanesulfonamide. Tumor growth inhibition was observed when an orally bioavailable analog was evaluated in a Karpas-299 tumor xenograft mouse model.
authors.affiliation: Worldwide Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. czificsa@cephalon.com
authors.forename: Craig A
authors.initials: CA
authors.lastname: Zificsak
authors.forename: Jay P
authors.initials: JP
authors.lastname: Theroff
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Aimone
authors.forename: Thelma S
authors.initials: TS
authors.lastname: Angeles
authors.forename: Mark S
authors.initials: MS
authors.lastname: Albom
authors.forename: Mangeng
authors.initials: M
authors.lastname: Cheng
authors.forename: Eugen F
authors.initials: EF
authors.lastname: Mesaros
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Ott
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Quail
authors.forename: Ted L
authors.initials: TL
authors.lastname: Underiner
authors.forename: Weihua
authors.initials: W
authors.lastname: Wan
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Dorsey
mesh_terms: D000284:Administration, Oral; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D003514:Cyclohexylamines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D007260:Infusion Pumps; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D011743:Pyrimidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D004791:Enzyme Inhibitors; D011743:Pyrimidines; C017205:2,4-diaminopyrimidine; C000626174:Alk protein, mouse; C000626175:Alk protein, rat; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases