- In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3- carbonitriles as JAK2 kinase inhibitors
-
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.
- 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
-
scheme or table
p. 2958 - 2961
(2011/06/26)
-
- PYRAZOLYLAMINOPYRIDINE DERIVATIVES USEFUL AS KINASE INHIBITORS
-
This invention relates to novel compounds having the Formula (I) to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.
- -
-
Page/Page column 109-110
(2008/06/13)
-
- Synthesis and biological evaluation of aroylguanidines related to amiloride as inhibitors of the human platelet Na+/H+ exchanger
-
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).
- Laeckmann, Didier,Rogister, Fran?oise,Dejardin, Jean-Victor,Prosperi-Meys, Christelle,Géczy, Joseph,Delarge, Jacques,Masereel, Bernard
-
p. 1793 - 1804
(2007/10/03)
-
- 2-methoxyimino-2-(pyridinyloxymethyl)phenyl acetamides with carboxylic acid derivatives on the pyridine ring
-
The present invention provides novel 2-methoximino-2-(pyridinyloxymethyl)phenyl acetamide compounds with carboxylic acid substituents on the pyridine ring, their use as fungicidal compounds, and their use in fungicidal compositions comprising at least one of the 2-methoximino-2-(pyridinyloxymethyl)phenyl acetamide compounds as the active ingredient.
- -
-
-
- Process for the manufacture of bromopyridines
-
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.
- -
-
-
- Process for the production of polyhalogenated nicotinic acids
-
A novel process for preparing 2,6-dichloro- and 2,5,6-trichloronicotinic acid is disclosed which comprises reacting 2,6-dichloro-3-chloromethylpyridine and 2,5,6-trichloro-3-chloromethylpyridine, respectively, with concentrated nitric acid in the presence of concentrated sulphuric acid and a metal salt catalyst. This process is both simple and economical; it is distinguished by high yields and low reaction temperatures while avoiding undesirable side-reactions.
- -
-
-