42530-05-2Relevant articles and documents
Inhibitors of c-Jun N-terminal kinases
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Page/Page column 40, (2008/06/13)
The present invention relates to compounds that are inhibitors of c-jun N-terminal kinase 1, 2, or 3 (JNK1, JNK2, or JNK3), compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders regulated by the activation of JNK1, JNK2 and JNK3.
Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity
Szczepankiewicz, Bruce G.,Kosogof, Christi,Nelson, Lissa T. J.,Liu, Gang,Liu, Bo,Zhao, Hongyu,Serby, Michael D.,Xin, Zhili,Liu, Mei,Gum, Rebecca J.,Haasch, Deanna L.,Wang, Sanyi,Clampit, Jill E.,Johnson, Eric F.,Lubben, Thomas H.,Stashko, Michael A.,Olejniczak, Edward T.,Sun, Chaohong,Dorwin, Sarah A.,Haskins, Kristi,Abad-Zapatero, Cele,Fry, Elizabeth H.,Hutchins, Charles W.,Sham, Hing L.,Rondinone, Cristina M.,Trevillyan, James M.
, p. 3563 - 3580 (2007/10/03)
The c-Jun N-terminal kinases (JNK-1, -2, and -3) are members of the mitogen activated protein (MAP) kinase family of enzymes. They are activated in response to certain cytokines, as well as by cellular stresses including chemotoxins, peroxides, and irradiation. They have been implicated in the pathology of a variety of different diseases with an inflammatory component including asthma, stroke, Alzheimer's disease, and type 2 diabetes mellitus. In this work, high-throughput screening identified a JNK inhibitor with an excellent kinase selectivity profile. Using X-ray crystallography and biochemical screening to guide our lead optimization, we prepared compounds with inhibitory potencies in the low-double-digit nanomolar range, activity in whole cells, and pharmacokinetics suitable for in vivo use. The new compounds were over 1000-fold selective for JNK-1 and -2 over other MAP kinases including ERK2, p38α, and p38δ and showed little inhibitory activity against a panel of 74 kinases.
Syntheses with Nitriles, LXIX. Isomeric Diamino Alkoxy Pyridine Carbonitriles-Separation and Application as Coupling Components
Junek, Hans,Uray, Georg,Kotzent, Anna
, p. 973 - 982 (2007/10/02)
The isomeric 4,6-diamino-2-alkoxy- (3), and 2,4-diamino-6-alkoxy-3-pyridine-carbonitriles (4) are obtained by treatment of 2-amino-1,1,3-tricyanopropene (1) with sodium alkoxides.Separation is based on their different pKα-values (3a = 2.01, 4a = 4.17).Coupling reaction of 3a-c with benzenediazonium chloride in strong acidic medium leads to the yellow azo dyes 5a-c, whereas coupling of 4a requires a buffered solution (pH 4-6) to yield 6.The UV-VIS spectra of the isomer pyridines and the azo dyes are discussed. - keywords: Azo Dyes; Diamino-alkoxy-pyridine-carbonitriles; UV-VIS spectra
Basic diaminopyridine-(3)-azo dyestuffs
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, (2008/06/13)
A basic azo dyestuff, which is free form acid groups conferring solubility in water, of the formula STR1 wherein two radicals Z represent groups of the formula --NR'R" and one radical Z represents a group of the formula --NR'R", --OR'" or --SR'", wherein R', R", and R'" each represents hydrogen, aryl, cycloalkyl or an aliphatic radical and R' and R" are able to form a ring containing the amino nitrogen and the radicals --NR'R" may be the same or different, R is alkyl, substituted alkyl or cycloalkyl, n is 1 or 2, Y represents a radical of the formula --CN or --CONH2, and D represents the radical of an aromatic or heterocyclic diazo component, and wherein at least one radical Z and/or D contains a basic, optionally cationic group. These dyestuffs are useful for dyeing and printing synthetic fibers to produce intensive and level dyeings with good fastness to light and general fastness properties.
