90807-80-0

Upstream product

• 7306-46-9 4-chloromethyl-1,2-dimethoxy-benzene 
• 21852-32-4 4-bromomethyl-1,2-dimethoxybenzene 
• 121-33-5 vanillin 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 93-03-8 (3,4-dimethoxyphenyl)methanol 

Downstream Products

• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 1335128-33-0 4-((4-chlorophenyl)(hydroxyl)methyl)-1-(3,4-dimethoxybenzyl)-1H-1,2,3-triazole 
• 1335128-42-1 4-((4-chlorophenyl)(methoxy)methyl)-1-(3-methoxy-4-methoxybenzyl)-1H-1,2,3-triazole 
• 1335128-43-2 4-((4-chlorophenyl)(ethoxy)methyl)-1-(3-methoxy-4-methoxybenzyl)-1H-1,2,3-triazole 
• 1335128-44-3 4-((4-chlorophenyl)(propoxy)methyl)-1-(3-methoxy-4-methoxybenzyl)-1H-1,2,3-triazole 
• 1335128-45-4 4-((4-chlorophenyl)(propargyloxy)methyl)-1-(3-methoxy-4-methoxybenzyl)-1H-1,2,3-triazole 

Relevant academic research and scientific papers

Interrupted CuAAC-Thiolation for the Construction of 1,2,3-Triazole-Fused Eight-Membered Heterocycles from O-/N-Propargyl derived Benzyl Thiosulfonates with Organic Azides

A copper(I)-catalyzed interrupted click-sulfenylation of O-/N-propargyl benzyl thiosulfonates with organic azides has been disclosed. The unified CuAAC-thiolation provides a wide range of triazole-fused eight-membered heterocycles in good to high (51–94%) yields under mild reaction conditions. Moreover, a three-component reaction is also achieved involving O-/N-propargyl benzyl thiosulfonates, benzyl bromide, and sodium azide to deliver fused-triazoles in 61–74% yields. From a synthetic point of view, the present protocol has been demonstrated at gram-scale reactions. A plausible mechanism is also proposed based on experimental results and control experiments. (Figure presented.).

New 3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one-based triazole derivatives: Design, synthesis, and biological evaluation as antiproliferative and apoptosis-inducing agents

A series of 1,2,3-triazole derivatives based on the quinoline–benzimidazole hybrid scaffold was designed, synthesized, and screened against a panel of NCI-60 humanoid cancer cell lines for in vitro cytotoxicity evaluation, which revealed that compound Q6 was the most potent cytotoxic agent with excellent GI50, TGI, and LC50 values on multiple cancer cell lines. Q6 was tested further on the BT-474 breast cancer line to evaluate the mechanism of action. Preliminary screening studies based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that compound Q6 had an excellent antiproliferative effect against human breast cancer cells, BT-474, with IC50 values of 0.59 ± 0.01 μM. The detailed study based on the acridine orange/ethidium bromide staining (AO/EB) and the 4′,6-diamidino-2-phenylindole (DAPI) assay suggested that the antiproliferative activity shown was due to the induction of apoptosis on exposure to Q6. Further, DCFDA staining showed the generation of reactive oxygen species, altering the mitochondrial potential and leading to the initiation of apoptosis. This was further supported by JC-1 staining, indicating that this scaffold can contribute to the development of more potent derivatives.

Synthesis and Studies of Potential Inhibitors of CD73 Based on a Triazole Scaffold

The ecto-5′-nucleotidase CD73 is involved in the production of immunosuppressive adenosine in the tumoral microenvironment and recently became a validated target in immuno-oncology. To avoid formation of CD73-produced adenosine, several series of potential inhibitors of the target enzyme based on a triazole scaffold were synthetized and evaluated on recombinant purified hCD73 and in cell-based assays.

Discovery and Characterization of 1 H-1,2,3-Triazole Derivatives as Novel Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy

The prostanoid EP4 receptor is one of the key receptors associated with inflammatory mediator PGE2-elicited immunosuppression in the tumor microenvironment. Blockade of EP4 signaling to enhance immunity-mediated tumor elimination has recently emerged as a promising strategy for cancer immunotherapy. In our efforts to discover novel subtype-selective EP4 antagonists, we designed and synthesized a class of 1H-1,2,3-triazole-based ligands that display low nanomolar antagonism activity toward the human EP4 receptor and excellent subtype selectivity. The most promising compound 59 exhibits single-digit nanomolar potency in the EP4 calcium flux and cAMP-response element reporter assays and effectively suppresses the expression of multiple immunosuppression-related genes in macrophage cells. On the basis of its favorable ADMET properties, compound 59 was chosen for further in vivo biological evaluation. Oral administration of compound 59 significantly inhibited tumor growth in the mouse CT26 colon carcinoma model accompanied by enhanced infiltration of cytotoxic T lymphocytes in the tumor tissue.

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.

Design and synthesis of imidazo[2,1-b]thiazole linked triazole conjugates: Microtubule-destabilizing agents

A series of imidazo[2,1-b]thiazole linked triazole conjugates were synthesized by using Huisgen 1,3-dipolar cyclo-addition reaction (click chemistry approach) and evaluated for their antiproliferative activity against some human cancer cell lines like, HeLa (cervical), DU-145 (prostate), A549 (lung), MCF-7 (breast) and HepG2 (liver). Among them, Conjugates 4g and 4h demonstrated a significant antiproliferative effect against human lung cancer cells (A549) with IC50values of 0.92 and 0.78 μM respectively. Flow cytometric analysis revealed that these conjugates induced cell cycle arrest in G2/M phase in A549 lung cancer cells. The tubulin polymerization assay and immunofluorescence analysis showed that these conjugates effectively inhibit microtubule assembly in cell free and cell based (A549) experiment respectively. Moreover, the apoptosis inducing properties were evaluated by Hoechst staining, mitochondrial membrane potential and Annexin V-FITC assay. Further, western blot analysis was performed for proapoptotic protein Bax and antiapoptotic protein Bcl-2 and the results demonstrated that there was up regulation of Bax and down regulation of Bcl-2 suggesting that these compounds induced apoptosis in human lung cancer cells, A549.

Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors

1,2,3-Triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates (5a–v) were designed, synthesized and evaluated for their cytotoxic potency against some human cancer cell lines like DU-145 (prostate), HeLa (cervical), MCF-7 (breast) HepG2 (liver) and A549 (lung). Preliminary results revealed that some of these conjugates like 5f and 5k exhibited significant antiproliferative effect against human breast cancer cells (MCF-7) with IC50 values of 0.60 and 0.78?μM respectively. Flow cytometric analysis of the cell cycle demonstrated an increase in the percentage of cells in the G2/M phase which was further authenticated by elevation of cyclin B1 protein levels. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 5f and 5k, and western blot analysis revealed that these conjugates accumulated more tubulin in the soluble fraction. Moreover, the conjugates caused apoptosis of the cells that was confirmed by mitochondrial membrane potential and Annexin V-FITC assay. Molecular docking studies indicated that these conjugates occupy the colchicine binding site of the tubulin protein.

Synthesis of 2-anilinopyridyl-triazole conjugates as antimitotic agents

A series of 2-anilinopyridyl-triazole conjugates (6a-t) were prepared and evaluated for their cytotoxic activity against a panel of three human cancer cell lines. Among them compounds 6q, 6r and 6s showed significant cytotoxic activity with IC50 values ranging from 0.1 to 4.1 μM. Structure-activity relationships were elucidated with various substitutions on these conjugates. Flow cytometric analysis revealed that these compounds arrest the cell cycle at the G2/M phase and induce cell death by apoptosis. The tubulin polymerization assay and immunofluorescence analysis showed that these compounds (6q, 6r and 6s) effectively inhibited the microtubule assembly in human prostate cancer cells (DU-145). The docking studies showed that 6s interacts and binds efficiently with the tubulin protein at the colchicine binding site. This was further confirmed by the colchicine competitive binding assay. Moreover, compounds 6q, 6r and 6s possess anti-tubulin activity both in vitro and within cells as demonstrated by the ratio of soluble versus polymerized tubulin. Further the apoptotic effects of compounds were confirmed by Hoechst staining, caspase 3 activation, annexin-V FITC, mitochondrial membrane potential and DNA fragmentation analysis. Interestingly, these compounds did not affect the normal human embryonic kidney cells, HEK-293.

Synthesis and biological evaluation of pyrazolo-triazole hybrids as cytotoxic and apoptosis inducing agents

A series of pyrazolo-triazole hybrids were designed and synthesized by combining the 1,3-diphenyl pyrazole and triazole scaffolds to obtain (1-benzyl-1H-1,2,3-triazol-4-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methanones. All the synthesized compounds were screened for their anticancer activity against four tumor cell lines, viz. HT-29 (colon), PC-3 (prostate), A549 (lung), and U87MG (glioblastoma) cells. Most of the tested compounds showed moderate to potent cell growth inhibition on different cancer cells, in particular, the compounds 17, 23, and 29 exhibited promising cytotoxicity against these cell lines with the IC50 values in the range of 0.86-3.72 μM. In addition, the potential mechanism of cell growth inhibition and apoptotic induction by these compounds was investigated in U87MG cancer cells using cell-based assays, including wound healing assay, flow cytometry, Hoechst staining, acridine orange/ethidium bromide staining, Annexin V-FITC/propidium Iodide dual staining, Rhodamine 123 staining, and carboxy-DCFDA staining. The results indicate that the compounds induce apoptosis in U87MG cells via mitochondrial pathway through up-regulation of pro-apoptotic (Bax) and down-regulation of anti-apoptotic (Bcl-2) genes. Based on these studies, three compounds 17, 23 and 29 have been identified as promising new molecules that have the potential to be developed as leads.

A new method for the synthesis of 1,5-disubstituted 1,2,3-triazoles via triazolium salt intermediates

A new transition metal free procedure for the synthesis of 1,5-disubstituted 1,2,3-triazoles, which proceeds via a triazolium salt intermediate is described. Georg Thieme Verlag KG Stuttgart · New York.