1027509-13-2Relevant academic research and scientific papers
Discovery of new orally active phosphodiesterase (PDE4) inhibitors
Ochiai, Hiroshi,Ishida, Akiharu,Ohtani, Tazumi,Kusumi, Kensuke,Kishikawa, Katuya,Yamamoto, Susumu,Takeda, Hiroshi,Obata, Takaaki,Nakai, Hisao,Toda, Masaaki
, p. 1098 - 1104 (2007/10/03)
A series of 4-anilinopyrazolopyridine derivatives were synthesized and biologically evaluated as inhibitors of phosphodiesterase (PDE4). Chemical modification of 3, a structurally new chemical lead that was found in our in-house library, was focused on 1- and 3-substituents. Full details of the discovery of a new orally active chemical lead 5 are presented. Structure-activity relationship data, pharmacological evaluation, and the subtype selectivity study are also presented.
N-Arylpiperazinyl-N'-propylamino derivatives of heteroaryl amides as functional uroselective α1-adrenoceptor antagonists
Elworthy, Todd R.,Ford, Anthony P. D. W.,Bantle, Gary W.,Morgans Jr., David J.,Ozer, Rachel S.,Palmer, Wylie S.,Repke, David B.,Romero, Magarita,Sandoval, Leticia,Sjogren, Eric B.,Talamás, Francisco X.,Vazquez, Alfredo,Wu, Helen,Arredondo, Nicolas F.,Blue Jr., David R.,DeSousa, Andrea,Gross, Lisa M.,Kava, M. Shannon,Lesnick, John D.,Vimont, Rachel L.,Williams, Timothy J.,Zhu, Quan-Ming,Pfister, Jürg R.,Clarke, David E.
, p. 2674 - 2687 (2007/10/03)
Novel arylpiperazines were identified as α1-adrenoceptor (AR) subtype- selective antagonists by functional in vitro screening. 3-[4-(ortho- Substituted phenyl)piperazin-1:yl]propylamines were derivatized with N,N- dimethyl anthranilamides, nicotinamides, as well as carboxamides of quinoline, 1,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4- b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta were used as a 'negative screen' for the test antagonists. Binding to α1-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g. 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the α1-AR subtype prevalent in the human lower urinary tract (pA2 values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the α(1D)-AR.
