945843-07-2Relevant academic research and scientific papers
Design and synthesis of spirocyclic compounds as HCV replication inhibitors by targeting viral NS4B protein
Tai, Vincent W.-F.,Garrido, Dulce,Price, Daniel J.,Maynard, Andrew,Pouliot, Jeffrey J.,Xiong, Zhiping,Seal, John W.,Creech, Katrina L.,Kryn, Luz H.,Baughman, Todd M.,Peat, Andrew J.
, p. 2288 - 2294 (2014/05/20)
Two novel series of spirocyclic piperidine analogs appended to a pyrazolo[1,5-a]pyridine core were designed, synthesized and evaluated for their anti-HCV activity. A series of piperidine ketals afforded dispiro 6p which showed excellent in vitro anti-HCV activities (EC50 of 1.5 nM and 1.2 nM against genotype 1a and 1b replicons, respectively). A series of piperidine oxazolidinones afforded 27c which showed EC50's of 10.9 nM and 6.1 nM against 1a and 1b replicons, respectively. Both compounds 6p and 27c bound directly to non-structural NS4B protein in vitro (IC50's = 10.2 and 30.4 nM, respectively) and exhibited reduced potency in replicons containing resistance mutations encoding changes in the NS4B protein.
Oligospiroketals as novel molecular rods
Wessig, Pablo,Moellnitz, Kristian,Eiserbeck, Christiane
, p. 4859 - 4872 (2008/02/03)
A modular approach for the synthesis of molecular rods based on oligospiroketals has been developed. The strategy relies on different terminal and intermediate segments, which are joined by ketal formation between ketones and diols. For this purpose it was necessary to develop a new ketalization method to circumvent some problems related with the established methods. The terminal segments are either derived from 4-piperidinone or from 4-oxocyclohexane carboxylic acid whereas the intermediate segments rest on pentaerythritol and cyclohexane-1,4-dione. A series of trispiro (14-18), hexaspiro (19) and nonaspiro (20) compounds have been prepared and characterized. From these we realized that it is imperative to use solubility enhancing groups if more than seven rings are joined.
