78358-09-5

Upstream product

• 104-88-1 4-chlorobenzaldehyde 
• 124-63-0 methanesulfonyl chloride 
• 873-76-7 para-Chlorobenzyl alcohol 

Downstream Products

• 6279-35-2 2-(4'-chlorophenyl)-1-phenylethan-1-ol 
• 30203-87-3 1-chloro-4-(4-methylbenzyl)benzene 
• 55676-88-5 1-chloro-4-(2-methylbenzyl)benzene 
• 72681-90-4 p-chlorobenzyl octyl ether 
• 95110-79-5 2-(4-chlorophenyl)-1-cyclohexylethanone 
• 6332-83-8 2-(4-chlorophenyl)-1-phenylethanone 
• 311316-67-3 5-[[(4-chlorophenyl)methyl]thio]-1-phenyl-1H-tetrazole 
• 63877-95-2 4-chlorophenyl-2-thienylmethane 
• 4350-41-8 2-(4-chlorobenzyl)pyridine 

Relevant academic research and scientific papers

Synthesis of N-alkylated pyrazolo[3,4-d]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties

Fused pyrimidines, especially pyrazolo[3,4-d]pyrimidines, are among the most preferred building blocks for pharmacology studies, as they exhibit a broad spectrum of biological activity. In this study, new derivatives of pyrazolo[3,4-d]pyrimidine were synthesized by alkylation of the N1 nitrogen atom. We synthesized 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine 2 from commercially available aminopyrazolopyrimidine 1 using N-iodosuccinimide as an iodinating agent. The synthesis of compound 2 started with nucleophilic substitution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine with R–X (X: –OMs, –Br, –Cl), affording?N-alkylated pyrazolo[3,4-d]pyrimidine. We performed this synthesis using a weak inorganic base?and the mild temperature was also used for a two-step procedure to generate N-alkylated pyrazolo[3,4-d]pyrimidine derivatives. Also, all compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and the human carbonic anhydrase (hCA) isoforms I and II, with Ki values in the range of 15.41 ± 1.39–63.03 ± 10.68 nM for AChE, 17.68 ± 1.92–66.27 ± 5.43 nM for hCA I, and 8.41 ± 2.03–28.60 ± 7.32 nM for hCA II. Notably, compound 10 was the most selective and potent CA I inhibitor with a significant selectivity ratio of 26.90.

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.

One-pot preparation of Julia-Kocienski sulfides and sulfones from alcohols

A method for one-pot preparation of Julia-Kocienski sulfides and sulfones from alcohols and thiols is reported. A variety of primary alcohols were converted to the corresponding mesylates by methansulfonyl chloride and triethylamine in THF. After the reaction is complete, thiol (1 or 10) and either NaH or t-BuOK were added. The Julia-Kocienski sulfides 3, 9 and 11 were prepared by one-pot two steps procedure from alcohols in 76–96% yields (16 examples). Furthermore, after the sulfide formation, the reaction mixture was neutralized by p-toluenesulfonic acid and treated with H2O2 and ammonium molybdate in EtOH to give the Julia-Kocienski sulfones 4 in good yields except for trans-2-hexen-1-ol.

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.

Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry

The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50 = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10 μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100 μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.

Cobalt-Catalyzed Formation of Functionalized Diarylmethanes from Benzylmesylates and Aryl Halides

A simple cobalt-catalyzed reductive coupling protocol allowing the synthesis of functionalized diarylmethanes from benzyl mesylate is described. The possibility to directly use the benzyl alcohol as a result of a two-step reaction is also presented. This method tolerates a variety of functional groups. A benzyl radical is likely involved. (Figure presented.).

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 antiproliferative activity of 8-hydroxyquinoline derivatives containing a 1,2,3-triazole moiety

Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by performing coppercatalyzed Huisgen 1,3-dipolar cycloaddition ("click" reaction) between an 8-O-alkylated-quinoline containing a terminal alkyne and various aromatic or protected sugar azides. These compounds were evaluated in vitro for their antiproliferative activity on various cancer cell types. Protected sugar derivative 16 was the most active compound in the series, exhibiting potent antiproliferative activity and high selectivity toward ovarian cancer cells (OVCAR-03, GI50 -1); this derivative was more active than the reference drug doxorubicin (OVCAR-03, GI50 = 0.43 μg mL-1). In structureeactivity relationship (SAR) studies, the physico-chemical parameters of the compounds were evaluated and docking calculations were performed for the a-glucosidase active site to predict the possible mechanism of action of this series of compounds.