183801-30-1

Upstream product

• 199679-35-1 3-(4-trifluoromethoxyphenyl)acrylic acid 
• 183800-94-4 trans-4-(trifluoromethoxy)cinnamaldehyde 
• 659-28-9 p-trifluoromethoxybenzaldehyde 

Downstream Products

• 865536-53-4 tert-butyl (2-dimethylaminoethyl)-{4-methyl-6-[(E)-3-(4-trifluoromethoxyphenyl)acryloylamino]quinolin-2-yl}carbamate 
• 710328-36-2 4-{4-methyl-6-[3-(4-trifluoromethoxy-phenyl)-acryloylamino]-quinolin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester 
• 712267-18-0 (2R,6S)-2,6-Dimethyl-4-{4-methyl-6-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloylamino]-quinolin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester 
• 865350-57-8 (E)-3-(4-(trifluoromethoxy)phenyl)acrylamide 

Relevant academic research and scientific papers

Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives

This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3, OCF3, F) on the meta- of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho- and para-substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.

Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors

A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (KIs in the range of 0.50–50.5 nM), hCA IX (KIs of 1.8–228.5 nM), and hCA XII (KIs of 3.5–96.2 nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure–activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates.

Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine amide-cinnamamide hybrids

We report herein the design and synthesis of a series of novel imidazo[1,2- A]pyridine amide-cinnamamide hybrids linked via an alkyl carbon chain. All 38 new hybrids were evaluated for their antimycobacterial activity against M. tuberculosis (MTB) H37Rv ATCC 27294 using the microplate Alamar Blue assay (MABA). Although the hybrids are less active than the two reference compounds, the promising activity (MICs: 4 μg/mL) of 2,6-dimethylimidazo[1,2-a]pyridine amide-cinnamamide hybrids 11e and 11k could be a good starting point to further find new lead compounds against multi-drug-resistant tuberculosis.

Quinazolinone and isoquinolinone derivative

The present invention relates to quinazolinone and isoquinolinone derivatives represented by formula (I) or pharmaceutically acceptable salts thereof.

Benzo[d]imidazole transient receptor potential vanilloid 1 antagonists for the treatment of pain: Discovery of trans-2-(2-{2-[2-(4-Trifluoromethyl-phenyl)-vinyl]-1H-benzimidazol-5-yl}-phenyl)-propan-2-ol (Mavatrep)

Reported herein is the design, synthesis, and pharmacologic characterization of a class of TRPV1 antagonists constructed on a benzo[d]imidazole platform that evolved from a biaryl amide lead. This design composes three sections: a 2-substituted 5-phenyl headgroup attached to the benzo[d]imidazole platform, which is tethered at the two position to a phenyl tail group. Optimization of this design led to the identification of 4 (mavatrep), comprising a trifluoromethyl-phenyl-vinyl tail. In a TRPV1 functional assay, using cells expressing recombinant human TRPV1 channels, 4 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 4.6 nM. In the complete Freund's adjuvant- and carrageenan-induced thermal hypersensitivity models, 4 exhibited full efficacy, with ED80 values of 7.8 and 0.5 mg/kg, respectively, corresponding to plasma levels of 270.8 and 9.2 ng/mL, respectively. On the basis of its superior pharmacologic and safety profile, 4 (mavatrep) was selected for clinical development for the treatment of pain.