2082-12-4

Upstream product

• 4740-22-1 2-amino-1-(4-nitro-phenyl)-ethanone 
• 100-19-6 (4-nitrophenyl)ethanone 
• 99-81-0 4-Nitrophenacyl bromide 
• 5425-81-0 2-amino-1-(4-nitrophenyl)ethanone hydrochloride 
• 4755-77-5 Ethyl oxalyl chloride 

Downstream Products

• 1441-38-9 ethyl 5-(4-nitrophenyl)oxazole-2-carboxylate 
• 1300747-66-3 ethyl 5-(4-nitrophenyl)thiazole-2-carboxylate 
• 1300747-67-4 5-(4-nitrophenyl)thiazole-2-carboxylic acid 

Relevant academic research and scientific papers

Synthesis, characterization, and biological evaluation of new derivatives targeting MbtI as antitubercular agents

Tuberculosis (TB) causes millions of deaths every year, ranking as one of the most dangerous infectious diseases worldwide. Because several pathogenic strains of Mycobacterium tuberculosis (Mtb) have developed resistance against most of the established anti-TB drugs, new therapeutic options are urgently needed. An attractive target for the development of new antitubercular agents is the salicylate synthase MbtI, an essential enzyme for the mycobacterial siderophore biochemical machinery, absent in human cells. A set of analogues of I and II, two of the most potent MbtI inhibitors identified to date, was synthesized, characterized, and tested to elucidate the structural requirements for achieving an efficient MbtI inhibition and a potent antitubercular activity with this class of compounds. The structure-activity relationships (SAR) here discussed evidenced the importance of the furan as part of the pharmacophore and led to the preparation of six new compounds (IV-IX), which gave us the opportunity to examine a hitherto unexplored position of the phenyl ring. Among them emerged 5-(3-cyano-5-(trifluoromethyl)phenyl)furan-2-carboxylic acid (IV), endowed with comparable inhibitory properties to the previous leads, but a better antitubercular activity, which is a key issue in MbtI inhibitor research. Therefore, compound IV offers promising prospects for future studies on the development of novel agents against mycobacterial infections.

Synthesis and evaluation of cyclohexane carboxylic acid head group containing isoxazole and thiazole analogs as DGAT1 inhibitors

Diacylglycerol acyltransferase 1 (DGAT1) is known to play an important catalytic role in the final step of triglyceride biosynthesis. High fat diet fed DGAT1 knockout mice were resistant to weight gain and exhibited increased insulin and leptin sensitivity thereby indicating a plausible role for DGAT1 inhibitors in the treatment of obesity. 4-Phenylpiperidine-1-carbonyl cyclohexanecarboxylic acid (compound 6, DGAT1 IC50 = 57 nM) has been lately reported as a potent DGAT1 inhibitor. In our search for newer scaffolds possessing potent DGAT1 activity we undertook a systematic diversification of compound 6 to identify a 4-(5-phenylthiazole-2-carboxamido)cyclohexanecarboxylic acid scaffold. Further linker optimization of this scaffold identified compound 9e (DGAT1 IC50 = 14.8 nM) as a potent DGAT1 inhibitor. Coupled with its in vitro potency, compound 9e also exhibited 112 percent plasma triglyceride reduction at a 3 mpk dose in an oral fat tolerance test (FTT) when studied in Swiss mice.

Evaluation of thiazole containing biaryl analogs as diacylglycerol acyltransferase 1 (DGAT1) inhibitors

Biphenyl carboxylic acids, exemplified by compound 5, are known potent inhibitors of diacylglycerol acyltransferase, DGAT1, an enzyme involved in the final committed step of triglyceride biosynthesis. We have synthesized and evaluated 2-phenylthiazole, 4-

Synthesis and biological evaluation of isoxazole, oxazole, and oxadiazole containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors

Diacylglycerol acyltransferase, DGAT1, is a promising target enzyme for obesity due to its involvement in the committed step of triglyceride biosynthesis. Amino biphenyl carboxylic acids, exemplified by compound 4, are known potent inhibitors of hDGAT1. However the high cLogP and poor solubility of these biphenyl analogs might tend to limit their development. We have synthesized and evaluated compounds containing 3-phenylisoxazole, 5-phenyloxazole, and 3-phenyl-1,2,4-oxadiazole biaryl units for their hDGAT1 inhibition. Our aim in synthesizing such heterocyclic analogs was to improve the cLogP and solubility of these molecules while retaining hDGAT1 potency. Several compounds within the 3-phenylisoxazole series exhibited potent hDGAT1 inhibition when evaluated using an in vitro enzymatic assay. Certain promising compounds were studied for their potential to reduce triglyceride levels using an in vivo fat tolerance test in mice and were also evaluated for any possible improvement to their solubility. Compound 40a (IC50 = 64 nM) with an in vivo plasma triglyceride reduction of 90 percent, and a solubility of 0.43 mg/ml at pH 7.4 may serve as a new lead for developing newer anti-obesity agents.

HETEROARYL COMPOUNDS AS DGAT-1 1NHIBITORS

The present invention relates to novel heteroaryl compounds, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or disorders mediated by Diacylglycerol acyltransferase (DGAT) enzyme, particularly DGAT- 1.