54718-39-7Relevant articles and documents
In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3- carbonitriles as JAK2 kinase inhibitors
Wang, Tao,Ioannidis, Stephanos,Almeida, Lynsie,Block, Michael H.,Davies, Audrey M.,Lamb, Michelle L.,Scott, David A.,Su, Mei,Zhang, Hai-Jun,Alimzhanov, Marat,Bebernitz, Geraldine,Bell, Kirsten,Zinda, Michael
, p. 2958 - 2961 (2011/06/26)
Synthesis and biological evaluation of a series of 6-aminopyrazolyl- pyridine-3-carbonitriles as JAK2 kinase inhibitors was reported. Biochemical screening, followed by profile optimization, resulted in JAK2 inhibitors exhibiting good kinase selectivity, pharmacokinetic properties, physical properties and pharmacodynamic effects.
Synthesis and biological evaluation of aroylguanidines related to amiloride as inhibitors of the human platelet Na+/H+ exchanger
Laeckmann, Didier,Rogister, Fran?oise,Dejardin, Jean-Victor,Prosperi-Meys, Christelle,Géczy, Joseph,Delarge, Jacques,Masereel, Bernard
, p. 1793 - 1804 (2007/10/03)
Pyridine and benzene bioisosteres of amiloride were synthesized and evaluated for their inhibitory potency against the sodium-hydrogen exchanger (NHE) involved in intracellular pH regulation. The inhibition of NHE was determined by using the platelet swelling assay (PSA) in which the swelling of human platelets was induced by their incubation in an acid buffer (pH 6.7). Additionally, the inhibitory potency of the most active compounds was assessed by measuring the inhibition of the EIPA-sensitive 22Na+ uptake (UIA) by human platelets after intracellular acidosis. The results indicated that several benzene derivatives and compounds bearing an carbonylguanidine moiety in the meta position of the pyridine nitrogen were much more potent than amiloride (PSA:IC50=43.5 μM; UIA:IC50=100.1 μM), but less than EIPA, a pyrazine NHE inhibitor (PSA:IC50=0.08 μM; UIA:IC50=0.5 μM). In both biological assays (2-amino-5-bromo-pyridine-3-carbonyl)guanidine (32) was the most active molecule (PSA:IC50=0.8 μM, UIA:IC50=0.8 μM). Our investigations demonstrated that the replacement of the pyrazine ring of amiloride by a pyridine or a phenyl ring improved the NHE inhibitory potency (phenyl >pyridine >pyrazine).
Process for the manufacture of bromopyridines
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, (2008/06/13)
A novel process for the preparation of 2,4-dibromo-, 2,6-dibromo- and 2,4,6-tribromopyridines, and the new bromopyridines to be obtained therewith, are disclosed. The novel process comprises treating 2,4-dichloro-, 2,6-dichloro- and 2,4,6-trichloropyridines, in an anhydrous organic medium, with gaseous HBr at temperatures between 80° and 130°C, said process being both simple and economical.