217661-99-9Relevant academic research and scientific papers
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.
Trisubstituted thiazoles as potent and selective inhibitors of Plasmodium falciparum protein kinase G (PfPKG)
Tsagris, Denise J.,Birchall, Kristian,Bouloc, Nathalie,Large, Jonathan M.,Merritt, Andy,Smiljanic-Hurley, Ela,Wheldon, Mary,Ansell, Keith H.,Kettleborough, Catherine,Whalley, David,Stewart, Lindsay B.,Bowyer, Paul W.,Baker, David A.,Osborne, Simon A.
, p. 3168 - 3173 (2018/09/11)
A series of trisubstituted thiazoles have been identified as potent inhibitors of Plasmodium falciparum (Pf) cGMP-dependent protein kinase (PfPKG) through template hopping from known Eimeria PKG (EtPKG) inhibitors. The thiazole series has yielded compounds with improved potency, kinase selectivity and good in vitro ADME properties. These compounds could be useful tools in the development of new anti-malarial drugs in the fight against drug resistant malaria.
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
4-(pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-dependent kinase 4/6
Cho, Young Shin,Borland, Maria,Brain, Christopher,Chen, Christine H.-T.,Cheng, Hong,Chopra, Rajiv,Chung, Kristy,Groarke, James,He, Guo,Hou, Ying,Kim, Sunkyu,Kovats, Steven,Lu, Yipin,O'Reilly, Marc,Shen, Junqing,Smith, Troy,Trakshel, Gary,V?gtle, Markus,Xu, Mei,Xu, Ming,Sung, Moo Je
experimental part, p. 7938 - 7957 (2011/03/19)
Identification and structure-guided optimization of a series of 4-(pyrazol-4-yl)-pyrimidines as selective CDK4/6 inhibitors is reported herein. Several potency and selectivity determinants were established based on the X-ray crystallographic analysis of representative compounds bound to monomeric CDK6. Significant selectivity for CDK4/6 over CDK1 and CDK2 was demonstrated with several compounds in both enzymatic and cellular assays.
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
Synthesis and biological evaluation of trisubstituted imidazole derivatives as inhibitors of p38α mitogen-activated protein kinase
Kim, Dae-Kee,Lim, Jin-Hwi,Lee, Jung A.,Dewang, Purushottam M.
scheme or table, p. 4006 - 4010 (2009/04/06)
A series of trisubstituted imidazole derivatives containing a 4-fluorophenyl group, a pyrimidine ring, and a CN- or CONH2-substituted benzyl moiety have been synthesized and evaluated for p38α MAP kinase inhibitory activity. Among them, compounds 22c, 27b, and 28b inhibited p38α MAP kinase with IC50 values 27.6, 28, and 31 nM, respectively.
Synthesis and biological activity of imidazopyridine anticoccidial agents: Part I
Scribner, Andrew,Dennis, Richard,Hong, Jean,Lee, Shuliang,McIntyre, Donald,Perrey, David,Feng, Dennis,Fisher, Michael,Wyvratt, Matthew,Leavitt, Penny,Liberator, Paul,Gurnett, Anne,Brown, Chris,Mathew, John,Thompson, Donald,Schmatz, Dennis,Biftu, Tesfaye
, p. 1334 - 1357 (2008/09/17)
Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance
Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents
Biftu, Tesfaye,Feng, Dennis,Fisher, Michael,Liang, Gui-Bai,Qian, Xiaoxia,Scribner, Andrew,Dennis, Richard,Lee, Shuliang,Liberator, Paul A.,Brown, Chris,Gurnett, Anne,Leavitt, Penny S.,Thompson, Donald,Mathew, John,Misura, Andrew,Samaras, Samantha,Tamas, Tamas,Sina, Joseph F.,McNulty, Kathleen A.,McKnight, Crystal G.,Schmatz, Dennis M.,Wyvratt, Matthew
, p. 2479 - 2483 (2007/10/03)
Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chi
Synthesis and SAR of 2-(4-fluorophenyl)-3-pyrimidin-4-ylimidazo[1,2-a]pyridine derivatives as anticoccidial agents
Feng, Dennis,Fisher, Michael,Liang, Gui-Bai,Qian, Xiaoxia,Brown, Chris,Gurnett, Anne,Leavitt, Penny Sue,Liberator, Paul A.,Mathew, John,Misura, Andrew,Samaras, Samantha,Tamas, Tamas,Schmatz, Dennis M.,Wyvratt, Matthew,Biftu, Tesfaye
, p. 5978 - 5981 (2007/10/03)
Compounds 10a-10d and 10i are very potent inhibitors of Eimeria tenella cGMP-dependent protein kinase (0.081-0.32 nM) and are very efficacious antiparasitic agents in vivo when administered to chickens at 12.5-25 ppm levels in the feed.
