Methanesulfonamido-cyclohexylamine derivatives of 2,4-diaminopyrimidine as potent ALK inhibitors

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...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2011-07, Vol.21 (13), p.3877-3880
Hauptverfasser:	Zificsak, Craig A, Theroff, Jay P, Aimone, Lisa D, Angeles, Thelma S, Albom, Mark S, Cheng, Mangeng, Mesaros, Eugen F, Ott, Gregory R, Quail, Matthew R, Underiner, Ted L, Wan, Weihua, Dorsey, Bruce D
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral animal models Animals Antineoplastic agents Antineoplastic Agents - administration & dosage Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology Biological and medical sciences chemical derivatives Cyclohexylamines - administration & dosage Cyclohexylamines - chemical synthesis Cyclohexylamines - pharmacology Enzyme Activation - drug effects enzyme inhibitors Enzyme Inhibitors - administration & dosage Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacology General aspects Infusion Pumps Inhibitory Concentration 50 Medical sciences Mice Molecular Structure Neoplasms - drug therapy Pharmacology. Drug treatments pyrimidines Pyrimidines - administration & dosage Pyrimidines - chemical synthesis Pyrimidines - pharmacology Rats Rats, Sprague-Dawley Receptor Protein-Tyrosine Kinases - antagonists & inhibitors Xenograft Model Antitumor Assays
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2011.05.040