1380672-72-9

Upstream product

• 30766-11-1 5-bromoisonicotinic acid 
• 29682-15-3 methyl 5-bromopicolinate 
• 1201326-81-9 methyl 5-methanesulfonylpyridine-2-carboxylate 
• 1380672-71-8 N-(2-chlorophenyl)-5-(methylsulfonyl)picolinamide 

Downstream Products

• 1380672-90-1 N'-[(E)-3-[4-(2-chlorophenyl)-5-(5-methylsulfonyl-2-pyridyl)-1,2,4-triazol-3-yl]prop-2-enoyl]-2-methoxy-pyridine-4-carbohydrazide 
• 1380672-07-0 G₀₀₇-LK 
• 1380672-91-2 (E)-N′-(3-(4-(2-chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)acryloyl)-4-cyanobenzohydrazide 
• 1380672-08-1 2-(4-(2-chlorophenyl)-5-((E)-2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)vinyl)-4H-1,2,4-triazol-3-yl)-5-(methylsulfonyl)pyridine 
• 1380672-92-3 4-chloro-N'-[(E)-3-[4-(2-chlorophenyl)-5-(5-methylsulfonyl-2-pyridyl)-1,2,4-triazol-3-yl]prop-2-enoyl]benzohydrazide 
• 1380672-73-0 3-(4-(2-chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)acrylic acid 

Relevant academic research and scientific papers

Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor

Tankyrases 1 and 2 (TNKS1/2) are promising pharmacological biotargets with possible applications for the development of novel anticancer therapeutics. A focused structure-activity relationship study was conducted based on the tankyrase inhibitor JW74 (1). Chemical analoging of 1 improved the 1,2,4-triazole based core and led to 4-{5-[(E)-2-{4-(2-chlorophenyl)-5-[5- (methylsulfonyl)pyridin-2-yl]-4H-1,2,4-triazol-3-yl}ethenyl]-1,3, 4-oxadiazol-2-yl}benzonitrile (G007-LK), a potent, "rule of 5" compliant and a metabolically stable TNKS1/2 inhibitor. G007-LK (66) displayed high selectivity toward tankyrases 1 and 2 with biochemical IC50 values of 46 nM and 25 nM, respectively, and a cellular IC50 value of 50 nM combined with an excellent pharmacokinetic profile in mice. The PARP domain of TNKS2 was cocrystallized with 66, and the X-ray structure was determined at 2.8 ? resolution in the space group P3221. The structure revealed that 66 binds to unique structural features in the extended adenosine binding pocket which forms the structural basis for the compound's high target selectivity and specificity. Our study provides a significantly optimized compound for targeting TNKS1/2 in vitro and in vivo.

TRIAZOLE DERIVATIVES AS WNT SIGNALING PATHWAY INHIBITORS

The present invention relates to compounds of formula (I), to processes for their preparation, to pharmaceutical formulations containing such compounds and to their use in therapy: Such compounds find particular use in the treatment and/or prevention of conditions or diseases which are affected by over-activation of signaling in the Wnt pathway and increased presence of nuclear β-catenin. For example, these may be used in preventing and/or retarding proliferation of tumor cells and metastasis, for example carcinomas such as colon carcinomas.