202598-92-3

Upstream product

• 98-16-8 3-trifluoromethylaniline 
• 1885-14-9 phenyl chloroformate 

Downstream Products

• 448233-17-8 N-(3-trifluoromethylphenyl)hydrazinecarbamide 
• 1170321-80-8 3-endo-(phenylsulfonyl)-N-[3-(trifluoromethyl)phenyl]-8-azabicyclo[3.2.1]octane-8-carboxamide 

Relevant academic research and scientific papers

Discovery of AdipoRon analogues as novel AMPK activators without inhibiting mitochondrial complex I

Activation of AMPK emerges as a potential therapeutic approach to metabolic diseases. AdipoRon is claimed to be an adiponectin receptor agonist that activates AMPK through adiponectin receptor 1 (AdipoR1). However, AdipoRon also exhibits moderate inhibition of mitochondrial complex I, leading to increased risk of lactic acidosis. In order to find novel AdipoRon analogues that activate AMPK without inhibition of complex I, 27 analogues of AdipoRon were designed, synthesized and biologically evaluated. As results, benzyloxy arylamide B10 was identified as a potent AMPK activator without inhibition of complex I. B10 dose-dependently improved glucose tolerance in normal mice, and significantly lowered fasting blood glucose level and ameliorated insulin resistance in db/db diabetic mice. More importantly, unlike the pan-AMPK activator MK-8722, B10 did not cause cardiac hypertrophy, probably owing to its selective activation of AMPK in the muscle tissue but not in the heart tissue. Together, B10 represents a novel class of AMPK activators with promising therapeutic potential against metabolic disease.

Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects

Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC50 value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a “prodrug”. In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation.

Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3

Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the “A” phenyl ring and “B” phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G1/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor.

N-(3,5-dimethyladamantane-1-yl)-N'-substituted phenylurea compound as well as preparation method and application thereof

The invention belongs to the technical field of medicinal chemistry, in particular to N-(3,5-dimethyladamantane-1-yl)-N'-substituted phenylurea compounds as well as preparation methods and application thereof. The compounds have the structure shown in the formula I. The compounds are proved that the compounds can improve the image recognition memory, the working and learning memory, the spatial learning and memory ability of model rats and has good anti-alzheimer effects by the new object discrimination experiments, Y-maze experiments, positioning navigation and space exploration experiments in mats. The formula I is shown in the description.

CYCLOPROPANECARBOXAMIDO-SUBSTITUTE AROMATIC COMPOUNDS AS ANTI-TUMOR AGENTS

Provided are cyclopropanecarboxamido-substituted aromatic compounds that inhibit protein kinases and their use in anti-tumor area. In particular, tyrosine-kinase inhibitors and Raf-kinase inhibitors as anti-tumor agents, their preparation, pharmaceutical composition, and their use in the treatment of cancer are also provided.

TRPV1 modulators: Synthesis and in vitro evaluation of 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives

Abstract A series of new 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives was synthesized and evaluated as TRPV1 modulators in a Ca2+ channel assay in HEK-293 cells overexpressing the human recombinant TRPV1 channel. Structura