96258-56-9

Upstream product

• 349-95-1 4-(trifluoromethyl)benzylic alcohol 
• 124-63-0 methanesulfonyl chloride 

Downstream Products

• 222716-19-0 1-(azidomethyl)-4-(trifluoromethyl)benzene 
• 1000386-58-2 methyl 1-[[4-(trifluoromethyl)phenyl]methoxy]naphthalene-2-carboxylate 
• 192994-71-1 1-(4-trifluoromethylbenzyl)indole-4-carbaldehyde 

Relevant academic research and scientific papers

CFTR-MODULATING ARYLAMIDES

The present disclosure relates to heterocyclic compounds, pharmaceutically acceptable salts thereof, and pharmaceutical preparations thereof. Also described herein are compositions and the use of such compounds in methods of treating diseases and conditions mediated by deficient CFTR activity, in particular cystic fibrosis.

Synthesis of novel 1,2,3-triazole derivatives of isocoumarins and 3,4-dihydroisocoumarin with potential antiplasmodial activity in vitro

Background: Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, dem-onstrating the need for the development of new antimalarial drugs. Objective: Synthesis and in vitro antiplasmodial evaluation of triazole compounds derived from isocou-marins and a 3,4-dihydroisocoumarin. Methods: The compounds were synthesized in 4 to 6-step reactions with the formation of the triazole ring via the Copper(I)-catalyzed 1,3-dipolar cycloaddition between isocoumarin or 3,4-dihydroisocoumarin azides and terminal alkynes. This key reaction provided compounds with an un-precedented connection of isocoumarin or 3,4-dihydroisocoumarin and the 1,2,3-triazole ring. The products were tested for their antiplasmodial activity against a Plasmodium falciparum chloroquine resistant and sensitive strains (W2 and 3D7, respectively). Results: Thirty-one substances were efficiently obtained by the proposed routes with an overall yield of 25-53%. The active substances in the antiplasmodial test displayed IC50 values ranging from 0.68-2.89 μM and 0.85-2.07 μM against W2 and 3D7 strains, respectively. Conclusion: This study demonstrated the great potential of isocoumarin or 3,4-dihydroisocoumarin derivatives because practically all the tested substances were active against Plasmodium falciparum.

Synthesis of cinnamic acid derivatives and leishmanicidal activity against Leishmania braziliensis

Leishmania braziliensis is one of the pathogenic agents of cutaneous and mucocutanoeous leishmaniasis. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new potential antileishmanial drugs. An alternative to promote the discovery of new drugs would be the association of different chemical groups of bioactive compounds. Here we describe the synthesis and bioactivity evaluation against L. braziliensis of cinnamic acid derivatives possessing isobenzofuranone and 1,2,3-triazole functionalities. We tested 25 compounds at 10 μM concentration against extracellular promastigotes and intracellular amastigotes during macrophage infection. Most compounds were more active against amastigotes than to promastigotes. The derivatives (E)-3-oxo-1,3-dihydroisobenzofuran-5-yl-(3,4,5-trimethoxy) cinnamate (5c), (1-(3,4-difluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl cinnamate (9g), and (1-(2-bromobenzyl)-1H-1,2,3-triazol-4-yl)methyl cinnamate (9l) were the most effective presenting over 80% toxicity on L. braziliensis amastigotes. While compound 5c is a cinnamate with an isobenzofuranone portion, 9g and 9l are triazolic cinnamic acid derivatives. The action of these compounds was comparable to amphotericin B used as positive control. Ultrastructural analysis revealed that 5c-treated parasites showed impaired cytokinesis and apoptosis triggering. Taken together, these results highlight the potential of cinnamic acid derivatives in development of novel anti-leishmanial drugs.

Synthesis of nerol derivatives containing a 1,2,3-triazole moiety and evaluation of their activities against cancer cell lines

In the present investigation, a collection of twenty two nerol derivatives, containing 1,2,3-triazolic appendages, was synthesized and screened in vitro for their cytotoxic activity against HL60, Nalm6, and Jurkat human leukemia cells as well as against B16F10 (melanoma cell line). In most cases, derivatives were able to reduce cell viability. The most potent compound (Z)-4-(((3,7-dimethylocta-2,6-dien-1-yl)oxy)methyl)-1-(4-(trifluoromethoxy)benzyl)-1H-1,2,3 triazole showed antiproliferative activity against Jurkat cells and reduced B16F10 cell migration. Physicochemical properties of the compounds were calculated in order to evaluate their potential for drug development. Most of the evaluated physicochemical parameters seemed to be favorable for drug development. In addition, for a better understanding of the biological activity results, 3D quantitative structure-activity relationship (QSAR) studies were carried out. 3D-QSAR studies indicate that the anticancer activities observed for the cell lines HL60 and Jurkat may occur by a similar mechanism of action and the same was found for the Nalm6 and B16F10 cell lines.

Synthesis and leishmanicidal activity of eugenol derivatives bearing 1,2,3-triazole functionalities

In this paper, it is described the synthesis and the evaluation of the leishmanicidal activity of twenty-six eugenol derivatives bearing 1,2,3-triazole functionalities. The evaluation of the compounds on promastigotes of Leishmania amazonensis (WHOM/BR/75/Josefa) showed that eugenol derivatives present leishmanicidal activities with varying degrees of effectiveness. The most active compound, namely 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-methylbenzyl)-1H-1,2,3-triazole (7k) (IC50 = 7.4 ± 0.8 μmol L?1), also targeted Leishmania parasites inside peritoneal macrophages (IC50 = 1.6 μmol L?1) without interfering with cell viability. The cytotoxicity of 7k against macrophage cells presented IC50 of 211.9 μmol L?1 and the selective index was equal to 132.5. Under similar conditions, compound 7k was more effective than glucantime and pentamidine, two drugs currently in the clinic. In addition, theoretical calculations showed that this compound also presents most physicochemical and pharmacokinetic properties within the ranges expected for orally available drugs. It is believed that eugenol bearing 1,2,3-triazole functionalities may represent a scaffold to be explored toward the development of new agents to treat leishmaniasis.

Synthesis of potential anti-Trypanosoma cruzi azole-naftifine analogues by azide–alkyne click reaction

Twenty novel azole-naftifine analogues were obtained using azide–alkyne click reaction. Five of them were more potent than the positive control naftifine revealing an unprecedented antiproliferative effects against Trypanosoma cruzi.

Synthesis and phytotoxic activity of 1,2,3-triazole derivatives

Thirteen triazole derivatives bearing halogenated benzyl substituents were synthesized using the Cu-catalyzed azide-alkyne cycloaddition (CuAAC),a leading example of the click chemistry approach,as the key step. The biological activity of the compounds was evaluated,and it was found that these compounds interfere with the germination and radicle growth (shoots and roots) of two dicotyledonous species,Lactuca sativa and Cucumis sativus,and one monocotyledonous species,Allium cepa. The compounds showed predominantly inhibitory activity related to the evaluated species mainly at the concentration of 10-4 mol L-1. Some of them presented inhibitory activity comparable to 2,4-D (2,4-dichlorophenoxyacetic acid),used as positive control.

A metal-free catalytic system for the oxidation of benzylic methylenes and primary amines under solvent-free conditions

Iodine-pyridine-tert-butylhydroperoxide is developed as a green and efficient catalytic system for the oxidation of benzylic methylenes to ketones and primary amines to nitriles. The reaction conditions are quite mild and environmentally benign, no transition metals, organic solvents or hazard reagents being needed. The oxidation of benzylic methylenes gave the corresponding ketones in excellent yields with complete chemoselectivity, while the oxidation of primary amines was complete in several minutes, affording various nitriles in moderate to good yields.

Stabilization Demands of Diethyl Phosphonate Substituted Carbocations as Revealed by Substituent Effects

Trifluoroethanolyses of a series of mesylate derivatives of diethyl (1-aryl-1-hydroxymethyl)phosphonates, 9, gave a Hammett ρ value of -10.1 in the electron donor substituent region.This value was slightly less than the value of -11.6 seen in the corresponding benzyl mesylates, ArCH2OMs, 12, in hexafluoroisopropyl alcohol.These data suggest that the demand for aryl group stabilization in the intermediate phosphoryl-substituted cation 10 does not surpass that of the α-H analogues, the benzyl cations.Some other factor must therefore account for the relative ease of formation of cations 10, which have the electronegative diethyl phosphonate group attached directly to the cationic center.The likely factor is an offsetting cation stabilizing feature associated with the diethyl phosphonate group.The Hammett plots for both mesylates 9 and 12 show a break, with decreased ρ values (-6.1 and -5.1, respectively) being observed in the electron-withdrawing region of the plot.Solvent effect studies on 9-m-F suggested that a change to "borderline behavior" is the origin of the break in the Hammett plot.A mechanistic change to the kδ process could be ruled out.The triflate derivative of diethyl (1-hydroxyethyl)phosphonate, 14, gave mixtures of substitution and elimination products on solvolysis.Solvent effect studies indicated a largely nucleophilic mechanism, while isotope effect studies were in line with some cationic character in the transition state in the highly ionizing, nonnucleophilic hexafluoroisopropyl alcohol solvent.Ion pair formation or the SN2 (intermediate) mechanism could rationalize the behavior of 14 in more highly ionizing solvents.