PATENT HIGHLIGHT pubs.acs.org/acsmedchemlett
Pyrrolidinones as Modulators of Neurogenesis Gerard Rosse* Structure Guided Chemistry, Dart Neuroscience LLC, 7473 Lusk Boulevard, San Diego, California 92121, United States Adjunct Associate Professor, Department of Pharmacology and Physiology, College of Medicine, Drexel University, New College Building, 245 North 15th Street, Philadelphia, Pennsylvania 19102, United States Pyrrolidinones as Modulators of Neurogenesis
Title:
Patent/Patent Application Number: WO-2015107053-A1
Publication date:
July 23, 2015
Priority date:
January 20, 2014
Priority Application:
EP 2013-305365
Inventors:
Jakob-Roetne, R.; Wichmann R.; Peters J.-E.; Jagasia R.
Assignee Company:
F. Hoffmann La Roche AG, Switzerland
Disease Area:
Alzheimer’s disease, depression, anxiety disorder, stroke Therapeutic Target: Adult neurogenesis for neuroregeneration
Summary:
The present application claims a series of pyrrolidinones, imidazolidinones, and hexahydropyrimidinones for the stimulation of neurogenesis from neural stem cells. New functional neurons are generated from adult neural stem cells through the process of adult neurogenesis that occurs throughout life in the adult brain. Extensive evidence suggests that adult hippocampal neurogenesis correlates with cognitive and emotional capacity. The compounds described here are potentially useful in the treatment of a wide range of disorders such as schizophrenia, Alzheimer’s disease, depression, anxiety disorder, stroke, Parkinson’s disease, down syndrome, autism spectrum disorders, traumatic brain injury, and normal aging.
Important Compound Classes:
Definitions:
W is
CH2
or
CH2CH2 . X is CR3R4 or NR5.
Received: December 21, 2015 Published: January 04, 2016 r 2016 American Chemical Society
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dx.doi.org/10.1021/acsmedchemlett.5b00493 | ACS Med. Chem. Lett. 2016, 7, 15–16
ACS Medicinal Chemistry Letters
PATENT HIGHLIGHT
Key Structures:
Biological Assay:
The neurogenic properties of the compounds were evaluated based on the proliferation of human embryonic stem cell derived neural stem cells (NSCs). Compounds efficacy is measured by the increase in cells based on ATP levels. The values of EC150 from the dose response curve are determined for each test compound.
Pharmacological Data:
The EC150 is the compound concentration at which 150% activity of control (100%) is reached.
Synthesis:
The synthesis and neurogenic properties of 75 compounds are described.
’ AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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dx.doi.org/10.1021/acsmedchemlett.5b00493 |ACS Med. Chem. Lett. 2016, 7, 15–16
