217661-99-9Relevant articles and documents
Discovery of Imidazo[1,2- a]pyrazines and Pyrazolo[1,5- c]pyrimidines as TARP γ-8 Selective AMPAR Negative Modulators
Savall, Brad M.,Wu, Dongpei,Swanson, Devin M.,Seierstad, Mark,Wu, Nyantsz,Vives Martinez, Jorge,García Olmos, Beatriz,Lord, Brian,Coe, Kevin,Koudriakova, Tatiana,Lovenberg, Timothy W.,Carruthers, Nicholas I.,Maher, Michael P.,Ameriks, Michael K.
supporting information, p. 267 - 272 (2019/03/19)
This report discloses the discovery and characterization of imidazo[1,2-a]pyrazines and pyrazolo[1,5-c]pyrimidines as selective negative modulators of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) associated with transmembrane AMPAR regulatory protein γ-8. Imidazopyrazine 5 was initially identified as a promising γ-8 selective high-throughput screening hit, and subsequent structure-activity relationship optimization yielded subnanomolar, brain penetrant leads. Replacement of the imidazopyrazine core with an isosteric pyrazolopyrimidine scaffold improved microsomal stability and efflux liabilities to provide 26, JNJ-61432059. Following oral administration, 26 exhibited time- and dose-dependent AMPAR/γ-8 receptor occupancy in mouse hippocampus, which resulted in robust seizure protection in corneal kindling and pentylenetetrazole (PTZ) anticonvulsant models.
IMIDAZOPYRAZINES AND PYRAZOLOPYRIMIDINES AND THEIR USE AS AMPA RECEPTOR MODULATORS
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Page/Page column 85, (2016/12/26)
Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, N-oxides, or solvates thereof, [Formula should be inserted here] Also provided herein are pharmaceutical compositions, comprising compounds of Formula (I), and methods of
Pyrazolopyrimidines and pyrazolotriazines with potent activity against herpesviruses
Gudmundsson, Kristjan S.,Johns, Brian A.,Weatherhead, Jason
scheme or table, p. 5689 - 5692 (2010/04/05)
Synthesis of several pyrazolo[1,5-c]pyrimidines, pyrazolo[1,5-a]pyrimidines and pyrazolo[1,5-a][1,3,5]triazines with potent activity against herpes simplex viruses is described. Synthetic approaches allowing for variation of the substitution pattern are o