4101-33-1Relevant academic research and scientific papers
Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia
Helal, Christopher J.,Kang, Zhijun,Hou, Xinjun,Pandit, Jayvardhan,Chappie, Thomas A.,Humphrey, John M.,Marr, Eric S.,Fennell, Kimberly F.,Chenard, Lois K.,Fox, Carol,Schmidt, Christopher J.,Williams, Robert D.,Chapin, Douglas S.,Siuciak, Judith,Lebel, Lorraine,Menniti, Frank,Cianfrogna, Julia,Fonseca, Kari R.,Nelson, Frederick R.,O Connor, Rebecca,MacDougall, Mary,McDowell, Laura,Liras, Spiros
experimental part, p. 4536 - 4547 (2011/09/16)
Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability.
HETEROAROMATIC QUINOLINE-BASED COMPOUNDS
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Page/Page column 32, (2010/11/30)
The invention pertains to heteroaromatic compounds that serve as effective phosphodiesterase (PDE) inhibitors. The invention also relates to compounds which are selective inhibitors of PDE10. The invention further relates to intermediates for preparation of such compounds; pharmaceutical compositions comprising such compounds; and the use of such compounds in methods for treating certain central nervous system (CNS) or other disorders. The invention relates also to methods for treating neurodegenerative and psychiatric disorders, for example psychosis and disorders comprising deficient cognition as a symptom.
