2557-04-2

Upstream product

• 598-21-0 2-Bromoacetyl bromide 
• 88-17-5 2-(trifluoromethyl)benzenamine 

Downstream Products

• 387831-27-8 3-amino-N-(2'-(trifluoromethyl)phenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide 
• 712344-42-8 3-amino-N-(2′-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide 

Relevant academic research and scientific papers

Design, synthesis, antimicrobial evaluation and docking studies of urea-triazole-amide hybrids

A series of urea-1,2,3-triazole-amide hybrids was designed and synthesized via click reaction of urea derivatives containing a propargyl unit with 2-bromo-N-phenylacetamide derivatives and characterized by FTIR, NMR and HRMS data. The antimicrobial evalua

A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity

Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance - and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.

Synthesis, crystal structure and antimicrobial activity of 2-((2-(4-(1H-1,2,4-triazol-1-yl)phenyl)quinazolin-4-yl)oxy)-N-phenylacetamide derivatives against phytopathogens

Abstract: A total of eighteen 2-((2-(4-(1H-1,2,4-triazol-1-yl)phenyl)quinazolin-4-yl)oxy)-N-phenylacetamide derivatives were designed and synthesized, via hybrid pharmacophore approach. Among these compounds, chemical structure of compound 4a was unambiguously confirmed by means of single-crystal X-ray diffraction analysis. All the compounds were evaluated in vitro for their inhibition activity against several important phytopathogenic bacteria and fungi in agriculture. The obtained results indicated that several compounds demonstrated potent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo). For example, compounds 4c, 4g and 4q had EC50 values of 35.0, 36.5 and 32.4 μg/mL toward this bacterium, respectively, around 1.5 times more active than commercial bactericide bismerthiazol (EC50 = 89.8 μg/mL). Additionally, compounds 4j and 4p were found to display comparable antifungal activity against Gloeosporium fructigenum at 50 μg/mL, to commercial fungicide hymexazol. Finally, the relationships between antibacterial activities and molecular structures of this class of compounds were discussed in detail. Graphical abstract: [Figure not available: see fulltext.].

Synthesis of novel 1,2,4-triazole derivatives containing the quinazolinylpiperidinyl moiety and: N -(substituted phenyl)acetamide group as efficient bactericides against the phytopathogenic bacterium Xanthomonas oryzae pv. oryzae

A series of novel 1,2,4-triazole derivatives (7a-7p) containing the quinazolinylpiperidinyl moiety and N-(substituted phenyl)acetamide group were designed, synthesized and evaluated for their antimicrobial activities in vitro. These compounds were fully characterized by 1H NMR, 13C NMR, HRMS and IR spectra. Notably, the structure of compound 7p was further confirmed through the single-crystal X-ray diffraction method. The obtained bioassay results indicated that most of these compounds exhibited good to excellent antibacterial activities against the rice bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo). For example, compounds 7e, 7g, 7n, 7l, 7i, 7k, 7a and 7h had EC50 (half-maximal effective concentration) values of 34.5, 38.3, 39.0, 46.0, 47.5, 54.6, 55.0 and 58.2 μg mL-1 against the bacterium, respectively, which were significantly lower than the control agent Bismerthiazol (85.6 μg mL-1). Additionally, antifungal experiments demonstrated that all the compounds did possess weak inhibition capabilities against three phytopathogenic fungi at 50 μg mL-1, except in the cases of compounds 7e and 7p against the fungus Gibberella zeae. The above experimental results proved that 1,2,4-triazole derivatives bearing both a quinazolinylpiperidinyl fragment and N-(substituted phenyl)acetamide unit are promising candidates for the development of new agricultural bactericides against the pathogenic bacterium Xoo, deserving further investigation in the future.

Development of Small Molecules with a Noncanonical Binding Mode to HIV-1 Trans Activation Response (TAR) RNA

Small molecules that bind to RNA potently and specifically are relatively rare. The study of molecules that bind to the HIV-1 transactivation response (TAR) hairpin, a cis-acting HIV genomic element, has long been an important model system for the chemist

Synthesis and cytotoxicity of thieno[2,3-b]quinoline-2-carboxamide and cycloalkyl[b]thieno[3,2-e]pyridine-2-carboxamide derivatives

Seventy nine derivatives of thieno[2,3-b]quinolines, tetrahydrothieno[2,3-b]quinoline, dihydrocyclopenta[b]thieno[3,2-e]pyridine, cyclohepta[b]thieno[3,2-e]pyridine and hexahydrocycloocta[b]thieno[3,2-e]pyridine were either synthesized or obtained commercially and tested for their antiproliferative activity against HCT116, MDA-MB-468 and MDA-MB-231 human cancer cell lines. The most potent eight compounds were active against all cell lines with IC50 values in the 80–250 nM range. In general hexahydrocycloocta[b]thieno[3,2-e]pyridines were most active with increasing activity observed as larger cycloalkyl rings were fused to the pyridine ring.

DOPAMINE D2 RECEPTOR LIGANDS

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0- arrestin pathway and/or on the cAMP pathway.

A synthesis, in silico, in vitro and in vivo study of thieno[2,3-b]pyridine anticancer analogues

The anticancer activity of the thieno[2,3-b]pyridines was explored by altering the ring size of the cyclo-aliphatic moiety. Five-, six-, seven- and eight-membered derivatives were tested against the NCI60 tumour cell panel. According to this assay the mos

Synthesis and biological evaluations of sulfanyltriazoles as novel HIV-1 non-nucleoside reverse transcriptase inhibitors

A novel sulfanyltriazole was discovered as an HIV-1 non-nucleoside reverse transcriptase inhibitor via HTS using a cell-based assay. Chemical modifications and molecular modeling studies were carried out to establish its SAR and understand its interactions with the enzyme. These modifications led to the identification of sulfanyltriazoles with low nanomolar potency for inhibiting HIV-1 replication and promising activities against selected NNRTI resistant mutants. These novel and potent sulfanyltriazoles could serve as advanced leads for further optimization.