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Imidazopyridazine Inhibitors of PI3Kβ 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 Imidazopyridazine Inhibitors of PI3Kβ WO-2016097347-A1 Publication date: June 23, 2016 EP20141-99322 Priority date: December 19, 2014 Mevellec, L. A.; Meerpoel, L.; Coupa, S.; Poncelet, V. S.; Pilatte, I. N. C.; Pasquier, E. T. J.; Berthelot, D. J.; Querolle, O. A. G.; Meyer, C.; Angibaud, P. R.; Demestre, C. G. M.; Mercey, G. J. M. Janssen Pharmaceutica, NV, Belgium Cancer, autoimmune disorders, inflammation, neurodegeneration Biological Target: Phosphoinositide-3-kinase beta (PI3Kβ) The present application claims a series of imidazopyrazine derivatives as inhibitors of PI3Kβ. The compounds described here are potentially useful in the treatment of a wide range of disorders such as cancer, autoimmune disorders, inflammation, neurodegeneration, allergy, asthma, kidney diseases, platelet aggregation, and pancreatic cancer.
Title: Patent/Patent Application Number: Priority Application: Inventors: Assignee Company: Disease Area: Summary:
Important Compound Classes:
Definitions: Key Structures:
Y= CH2 or NH
Received: October 14, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acsmedchemlett.6b00406 ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX
ACS Medicinal Chemistry Letters Recent Review Articles:
Biological Assay:
Patent Highlight
1. Falasca, M., Hamilton, J. R., Selvadurai, M., Sundaram, K., Adamska, A., Thompson, P. E. Class II Phosphoinositide 3-Kinases as Novel Drug Targets. J. Med. Chem. 2016, DOI: 10.1021/acs.jmedchem.6b00963. 2. Mazumder, A. G.; Padwad, Y. S.; Singh, D. Anticancer Mammalian Target of Rapamycin (mTOR) Signaling Pathway Inhibitors: Current Status, Challenges and Future Prospects in Management of Epilepsy. CNS Neurol. Disorders: Drug Targets; 2016, 15 (8), 945−955. The inhibitor binding constants (Kd) of the compounds were determined using the KINOMEscan technology performed by DiscoverRx. The cellular activity of inhibitors was measured in an enzyme-linked immunosorbant assay by quantifying the Akt phosphorylation at Ser473 and Thr308 in PC-3 cells.
Pharmacological Data:
Synthesis
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The synthesis and biological activity of one hundred and ten compounds are described.
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The author declares no competing financial interest.
B
DOI: 10.1021/acsmedchemlett.6b00406 ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX
