1061602-00-3

Upstream product

• 540-51-2 2-bromoethanol 
• 581098-38-6 4-(4-fluorophenyl)-5-(2-fluoropyridin-4-yl)-1,3-dihydro-2H-imidazole-2-thione 
• 461-87-0 2-fluoro-4-methylpyridine 
• 451-46-7 4-fluorobenzoic acid ethyl ester 
• 457081-00-4 1-(4-fluorophenyl)-2-(2-fluoropyridin-4-yl)-2-(hydroxyimino)-ethan-1-one 
• 302839-09-4 1-(4-fluorophenyl)-2-(2-fluoropyridin-4-yl)ethan-1-one 

Downstream Products

• 1061602-02-5 (1R,4R)-4-(4-(4-(4-fluorophenyl)-2-(2-hydroxyethylthio)-1H-imidazol-5-yl)pyridin-2-ylamino)cyclohexanol 
• 1229571-96-3 (S)-4-(4-fluorophenyl)-5-[2-(3-methylbutan-2-ylamino)pyridin-4-yl]-1,3-dihydroimidazol-2-one 
• 1229571-97-4 (R)-4-(4-fluorophenyl)-5-[2-(1-phenylethylamino)pyridin-4-yl]-1,3-dihydroimidazol-2-one 
• 1012305-68-8 2-((4-(4-fluorophenyl)-5-(2-((3-methylbutan-2-yl)amino)pyridin-4-yl)-1H-imidazol-2-yl)thio)ethan-1-ol 
• 1229571-92-9 4-(4-fluorophenyl)-5-(2-((3-methylbutan-2-yl)amino)pyridine-4-yl)-1,3-dihydro-2H-imidazol-2-one 

Relevant academic research and scientific papers

KINASE MODULATORS FOR THE TREATMENT OF CANCER

A method of treating cancer in which a compound that inhibits the expression, production or release of IL-10 by immune cells is combined with a compound that stimulates the production of IL-12 when given in combination with, or in the presence of TNFa. Sa

An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors

An optimized strategy for the synthesis of the potent p38α mitogen-activated protein kinase inhibitors 2-(2-hydroxyethylsulfanyl)-4-(4-fluorophenyl)-5-(2-aminopyridin-4-yl)imidazole (3) and 2-(2,3-dihydroxypropylsulfanyl)-4-(4-fluorophenyl)-5-(2-aminopyridin-4-yl)imidazole (4) starting from 2-fluoro-4-methylpyridine is reported. In contrast to a previously published synthesis starting from 2-bromo-4-methylpyridine, the overall yield could be increased from 3.6% to 29.4%. Moreover, this strategy avoids the use of palladium as a catalyst and is more diverse and versatile. Using this optimized protocol, both enantiomers of potent inhibitor 3 were synthesized. Biological data demonstrated that the (S)-enantiomer is the two times more potent eutomer.

Unexpected reaction of 2-alkylsulfanylimidazoles to imidazol-2-ones: Pyridinylimidazol-2-ones as novel potent P38α mitogen-activated protein kinase inhibitors

While optimizing the synthesis of 2-alkylsulfanyl-5-(2-aminopyridin-4-yl) imidazoles, we identified an unexpected reaction to pyridinylimidazol-2-ones. 2-Alkylsulfanylimidazoles, bearing a 2-hydroxyethyl or a 2,3-dihydroxypropyl moiety at the imidazole C2-S position, were converted by heating into imidazol-2-ones. These imidazol-2-ones were tested for their ability to inhibit p38α MAP kinase and LPS-stimulated TNF-α release in HWB. Introduction of an amino moiety at the pyridine C2 position led to compounds showing potent enzyme inhibitory activity with double-digit nanomolar IC 50 values (5a: IC50 = 23 nM).

2-SULFANYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS

The invention relates to 2-thio-substituted imidazole derivatives of the Formula I, and to methods of use thereof.

Targeting the ribose and phosphate binding site of p38 mitogen-activated protein (MAP) kinase: Synthesis and biological testing of 2-alkylsulfanyl-, 4(5)-aryl-, 5(4)-heteroaryl-substituted imidazoles

Three series of substituted 2-alkylsulfanyl-4-(4-fluorophenyl)imidazoles, 5-pyridinyl-, 1-methyl-5-pyridinyl-, and 5-(2-aminopyridin-4-yl)-imidazoles, were prepared and tested for their ability to inhibit p38 MAP kinase and TNF-α release. These compounds