3598-91-2

Upstream product

• 22118-09-8 2-bromoacetyl chloride 
• 100-01-6 4-nitro-aniline 
• 598-21-0 2-Bromoacetyl bromide 

Downstream Products

• 52121-17-2 N-{5-nitro-3-[(4-nitro-phenylcarbamoyl)-methyl]-3H-thiazol-2-ylidene}-isonicotinamide 
• 362590-25-8 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(N-(4-nitrophenyl)acetamide) 
• 708279-23-6 2-(4-methylpiperazin-1-yl)-N-(4-nitrophenyl)acetamide 
• 1261166-62-4 C₁₇H₁₄N₄O₃ 
• 1309863-68-0 C₃₀H₂₄N₆O₆ 
• 300558-35-4 2-(4-tert-butylphenoxy)-N-(4'-nitrophen-1'-yl)acetamide 
• 3589-59-1 N-(4'-nitrophenyl)-2-amino-ethylacetate 
• 100970-41-0 [ethoxycarbonylmethyl-(4-nitrophenyl)amino]acetic acid ethyl ester 
• 1309666-87-2 5,11,17,23-tetra-tert-butyl-25,27-bis-[(ethoxycarbonyl)methoxy]-26,28-bis-[N-(4'-nitrophenyl)-aminocarbonylmethoxy]thiacalix[4]arene 
• 1370556-90-3 N-(4-nitrophenyl)diethylphosphonoacetamide 
• 1432790-79-8 C₁₆H₁₄N₆O₅S₂ 
• 313518-46-6 C₁₅H₁₆N₂O₂ 

Relevant academic research and scientific papers

Design, synthesis, anticancer and antioxidant activities of amide linked 1,4-disubstituted 1,2,3-triazoles

To explore anticancer and antioxidant agents with improved potency, we synthesized a series of amide linked 1,4-disubstituted 1,2,3-triazoles through click chemistry approach. The structure of synthesized triazoles were characterized by- FTIR, 1H NMR, 13C NMR spectroscopy and HRMS. All the synthesized compounds were screened for their anticancer activity against four different cell lines- PC3 (prostate cancer), A549 (lung cancer), MIAPACA (liver cancer), Fr2 (Breast epithelial), reflecting compounds 7e and 7f to possess good activity. The antioxidant activity was evaluated by using stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and compound 7d showed promising activity having IC50 value 1.61 μg/ml. Molecular docking studies of compounds 7e and 7f was carried out in active site of human epidermal growth factor receptor 2 revealed high binding affinities and within toxicity limits. The experimental results were in good agreement with docking studies. In-silico ADME studies of synthesized compounds also have good dispositional profile and are patient compliant, may be potential future candidates for anticancer treatment.

Identification of N-phenyl-2-(phenylsulfonyl)acetamides/propanamides as new SLC-0111 analogues: Synthesis and evaluation of the carbonic anhydrase inhibitory activities

As a front-runner selective CA IX inhibitor currently in Phase Ib/II clinical trials, SLC-0111 has been herein exploited as a lead molecule for development of new different sets of N-phenyl-2-(phenylsulfonyl)acetamides/propanamides incorporating different functionalities; primary sulfonamide (5a-f), free carboxylic (8a, 8d), ethyl ester (8b, 8e), acetyl (8c, 8f) and nitro (10a, 10b), as potential carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. All the prepared analogues have been examined for their CA inhibitory activities towards four human (h) isoenzymes, hCA I, II, IX and XII. Interestingly, replacement of SLC-0111 ureido linker with the flexible sulfonyl acetamide linker, as well as linker branching and elongation strategies successfully enhanced the inhibitory action toward hCA IX isoform, such as in sulfones 5a-d and 5f which displayed better activity than SLC-0111. Furthermore, sulfonamide-based sulfone (5f) and carboxylic acid-based sulfones (8a and 8d) demonstrated interesting selectivity toward the tumor-related hCA IX isoform over both hCA I and hCA II, which suggests them as promising candidates for further development as potential anticancer candidates. Thereafter, the anti-proliferative action for sulfones 5f, 8a and 8d was examined against breast (MCF-7) and colon (HCT-116) cancer cell lines. Also, sulfone 5f was further assessed for its impact on the cell cycle progression and apoptosis in HCT-116 cells.

Pyrazoline tethered 1,2,3-triazoles: Synthesis, antimicrobial evaluation and in silico studies

A new series of pyrazoline-amide linked 1,2,3-triazole hybrids was wisely designed and synthesized using 1,3-dipolar cycloaddition between pyrazoline linked alkynes and 2-bromo-N-arylacetamide. All the newly synthesized compounds were evaluated in vitro against different microbial strains viz. Escherichia coli, Bacillius subtilis, Staphylococcus aureus, Aspergillus niger, and Candida albicans. Pyrazoline linked terminal alkynes (4a–c) showed MIC = 0.062–0.078 μmol/mL against different bacterial and fungal strain. However, pyrazoline-amide linked 1,2,3-triazole hybrids (6a-6t) showed MIC = 0.0229–0.050 μmol/mL. Compound 6e exhibited better efficacy against E. coli and both the fungal strains compared to standard drugs used. Docking studies of the most potent compounds were carried out against bacterial DNA Gyr A and fungal 14α-steroldemethylase were also performed. The binding potential of 4a and 6e with both the target using molecular dynamics simulations was also investigated.

Design, synthesis, and biological evaluation of cyano-substituted 2,4-diarylaminopyrimidines as potent JAK3 inhibitors for the treatment of B-cell lymphoma

A series of cyano-substituted 2,4-diarylaminopyrimidines was designed and synthesized as potent non-covalent JAK3 inhibitors. Among the derivatives synthesized, 9o (IC50 = 22.86 nM), 9 k (IC50 = 21.58 nM), and 9j (IC50 = 20.66 nM) demonstrated inhibitory potencies against JAK3 similar to the known JAK3 inhibitor tofacitinib (IC50 = 20.10 nM). Moreover, 9o displayed potent anti-proliferative activities against Raji and Ramos cells, with IC50 values of 0.9255 μM and 1.405 μM, respectively. In addition, 9o demonstrated low toxicity in normal HBE (human bronchial epithelial cells, IC50 > 10 μΜ) and L-02 (human liver cells, IC50 = 3.104 μΜ) cells. Analysis of the mode of action by flow cytometry indicated that 9o effectively arrested Raji cells at the G2/M phase. Taken together, these results suggested that 9o might be a promising candidate for development as a potential treatment for B-cell lymphoma.

Novel Pyrimidines as Multitarget Protein Tyrosine Kinase Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)

A new class of pyrimidine derivatives were identified as potent protein tyrosine kinase (PTK) inhibitors for the treatment of idiopathic pulmonary fibrosis (IPF). Most of these small-molecule inhibitors displayed strong enzymatic activity against BTK and JAK3 kinases at concentrations lower than 10 nM. The representative compound N-(3-((5-chloro-2-(4-((1-morpholino)acetylamino)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide (6 a) also exhibited high inhibitory potency toward both BTK and JAK kinase families, as well as ErbB4, at a concentration of 10 nM, achieving rates of inhibition higher than 57 %. Additionally, in vivo biological evaluations showed that 6 a can remarkably decrease the severity of IPF disease. All these investigations suggested that the multi-PTK inhibitor 6 a may serve as a promising agent for the treatment of IPF.

Design and synthesis of diphenylpyrimidine derivatives (DPPYs) as potential dual EGFR T790M and FAK inhibitors against a diverse range of cancer cell lines

A new class of pyrimidine derivatives were designed and synthesized as potential dual FAK and EGFRT790M inhibitors using a fragment-based drug design strategy. This effort led to the identification of the two most active inhibitors, namely 9a and 9f, against both FAK (IC50 = 1.03 and 3.05 nM, respectively) and EGFRT790M (IC50 = 3.89 and 7.13 nM, respectively) kinase activity. Moreover, most of these compounds also exhibited strong antiproliferative activity against the three evaluated FAK-overexpressing pancreatic cancer (PC) cells (AsPC-1, BxPC-3, Panc-1) and two drug-resistant cancer cell lines (breast cancer MCF-7/adr cells and lung cancer H1975 cells) at concentrations lower than 6.936 μM. In addition, 9a was also effective in the in vivo assessment conducted in a FAK-driven human AsPC-1 cell xenograft mouse model. Overall, this study offers a new insight into the treatment of hard to treat cancers.

JAK3 inhibitors based on thieno[3,2-d]pyrimidine scaffold: design, synthesis and bioactivity evaluation for the treatment of B-cell lymphoma

JAK3 is predominantly expressed in hematopoietic cells and has been a promising therapeutic target for the treatment of B-cell lymphoma. In this study, a new class of thieno[3,2-d]pyrimidines harboring acrylamide pharmacophore were synthesized as potent covalent JAK3 inhibitors (IC50 50 values of 1.9 nM and 1.8 nM, respectively. Furthermore, compared with the reference agents, Spebrutinib and Ibrutinib, 9a not only demonstrated enhanced antiproliferative activity against B lymphoma cells, but also showed very weak proliferative inhibition against normal peripheral blood mononuclear cells (PBMCs) at a concentration of 20 μM. Analysis of the mechanism revealed that 9a could induce the obvious apoptosis in B lymphoma cells and prevent JAK3-STAT3 cascade as well as BTK pathway. Taken together, 9a may be served as a potential new JAK3 inhibitor for the treatment of B-cell lymphoma.

Design, synthesis of novel (Z)-2-(3-(4-((3-benzyl-2,4-dioxothiazolidin-5-ylidene)methyl)-1-phenyl-1H-pyrazol-3-yl)phenoxy)-N-arylacetamide derivatives: Evaluation of cytotoxic activity and molecular docking studies

In an attempt to discover potential cytotoxic agents, a series of novel (Z)-2-(3-(4-((3-benzyl-2,4-dioxothiazolidin-5-ylidene)methyl)-1-phenyl-1H-pyrazol-3-yl) phenoxy)-N-arylacetamide derivatives 11a-n were synthesized in varied steps with acceptable reaction procedures with good yields and characterized by 1H NMR, 13C NMR, IR and ESI-MS spectra. All the novel synthesized derivatives were assessed for their cytotoxic activity against human breast cell line (MCF-7) with different concentration of 0.625 μM, 1.25 μM, 2.5 μM, 5 μM and 10 μM respectively. Biological evaluation assay results were displayed in terms of percentage of cell viability reduction and IC50 values. Most of the screened derivatives demonstrated moderate to promising cytotoxic activity. Some of the derivatives, particularly compound 11d and 11n have shown promising cytotoxic activity with IC50 values 0.604 μM and 0.665 μM compared to standard drug cisplatin and compounds 11a, 11e and 11g also have shown considerable cytotoxic activity and the rest of the derivatives have shown moderate activity. Furthermore, molecular docking calculations and ADME properties of the synthesized molecules are in effective compliance with the cytotoxic evaluation results.

Amide-Based Cinchona Alkaloids as Phase-Transfer Catalysts: Synthesis and Potential Application

Herein we present a library of simple amide derivatives of Cinchona alkaloids in the form of quaternary ammonium salts. The obtained derivatives can be generated very easily and efficiently from inexpensive and commercially available substrates. We tested this class of alkaloids in the alkylation of glycine derivative, carried out under phase-transfer catalyst conditions. The presented hybrid catalysts offer both high reaction yields (up to 97%) and high enantioselectivities of the obtained product (up to 94% ee).

Efficient synthesis, antitubercular and antimicrobial evaluation of 1,4-disubstituted 1,2,3-triazoles with amide functionality

Abstract: A series of 21 amide linked 1,4-disubstituted-1,2,3-triazoles were achieved via one-pot synthesis through Cu(I) catalyzed click reaction between terminal alkynes and 2-azido-N-substituted acetamides. Newly formed triazoles were characterized by various spectroscopic techniques (FT-IR, 1H NMR, 13C NMR spectroscopy, and HRMS) and investigated for in vitro antitubercular evaluation against bacteria, i.e., Mycobacterium tuberculosis and antimicrobial evaluation against Bacillus subtilis, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger. Some of the synthesized triazole derivatives were found to exhibit moderate inhibitory activity against the tested antitubercular strain, whereas one compound displayed a significant inhibitory activity against most of the tested microbial strains. Graphical abstract: [Figure not available: see fulltext.].