title: 3,5-diarylazoles as novel and selective inhibitors of protein kinase D.
abstract: The synthesis and preliminary studies of the SAR of novel 3,5-diarylazole inhibitors of Protein Kinase D (PKD) are reported. Notably, optimized compounds in this class have been found to be active in cellular assays of phosphorylation-dependant HDAC5 nuclear export, orally bioavailable, and highly selective versus a panel of additional putative histone deacetylase (HDAC) kinases. Therefore these compounds could provide attractive tools for the further study of PKD/HDAC5 signaling.
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA. gabriel.gamber@novartis.com
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Gamber
authors.forename: Erik
authors.initials: E
authors.lastname: Meredith
authors.forename: Qingming
authors.initials: Q
authors.lastname: Zhu
authors.forename: Wanlin
authors.initials: W
authors.lastname: Yan
authors.forename: Chang
authors.initials: C
authors.lastname: Rao
authors.forename: Michael
authors.initials: M
authors.lastname: Capparelli
authors.forename: Robin
authors.initials: R
authors.lastname: Burgis
authors.forename: Istvan
authors.initials: I
authors.lastname: Enyedy
authors.forename: Ji-Hu
authors.initials: JH
authors.lastname: Zhang
authors.forename: Nicolas
authors.initials: N
authors.lastname: Soldermann
authors.forename: Kimberley
authors.initials: K
authors.lastname: Beattie
authors.forename: Olga
authors.initials: O
authors.lastname: Rozhitskaya
authors.forename: Keith A
authors.initials: KA
authors.lastname: Koch
authors.forename: Nikos
authors.initials: N
authors.lastname: Pagratis
authors.forename: Vinayak
authors.initials: V
authors.lastname: Hosagrahara
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vega
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McKinsey
authors.forename: Lauren
authors.initials: L
authors.lastname: Monovich
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D006655:Histone Deacetylases / Q000378:metabolism; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D001393:Azoles; D047428:Protein Kinase Inhibitors; C089212:protein kinase D; D011493:Protein Kinase C; C498619:Hdac5 protein, rat; D006655:Histone Deacetylases