Category: imidazoles-derivatives

Guemues, Selcuk published the artcileSubstituent effect on the aromaticity of 1,3-azole systems, Application of 5-Fluoro-1H-imidazole, the main research area is oxazole imidazole thiazole substituent effect aromaticity.

The effects of substituent type and position on the aromaticity of certain derivatives of oxazole, imidazole and thiazole have been theor. investigated by using d. functional theory at the levels of B3LYP/6-31G(d,p) and B3LYP/6-31++G(d,p) methods. The second heteroatom substitution decreased aromaticity of furan, pyrrole and thiophene. The decreased aromaticity was gained back to some extent by the substitution of strong electron withdrawing groups or atoms (NO2 and F). Nucleus-independent chem. shift (NICS) data have been considered to determine the aromaticity of the systems. The most effective substitution to enhance the aromaticity has been calculated to be at position 4. The variation of the bond lengths of the main skeleton supported the findings through NICS calculations The frontier MO energies have also been reported to draw a general correlation between these energies and the aromaticity of the system.

Heterocyclic Communications published new progress about Aromaticity. 30086-17-0 belongs to class imidazoles-derivatives, name is 5-Fluoro-1H-imidazole, and the molecular formula is C3H3FN2, Application of 5-Fluoro-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Garuti, Laura published the artcileSynthesis and antiviral/antiproliferative activity of some N-sulphonylbenzimidazoles, Recommanded Product: Methyl 1H-benzo[d]imidazole-2-carboxylate, the main research area is benzimidazolyl sulfone antiviral antiproliferative preparation.

Some benzimidazolyl sulfones were synthesized and evaluated for their antiviral and antiproliferative properties. I (R = CHMe2) displayed significant and selective activity against human cytomegalovirus (CMV), I (R = 3-NO2-C6H4) showed activity against varicella zoster virus (VZV). The compounds were further evaluated for inhibitory effect on the proliferation of murine leukemia cells and human T-lymphocyte cells. Marked cytotoxicity was noted with different derivatives Some structure-activity relationships are discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 5805-53-8 belongs to class imidazoles-derivatives, name is Methyl 1H-benzo[d]imidazole-2-carboxylate, and the molecular formula is C9H8N2O2, Recommanded Product: Methyl 1H-benzo[d]imidazole-2-carboxylate.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Xing, Jing published the artcileRational design of 5-((1H-imidazol-1-yl)methyl)quinolin-8-ol derivatives as novel bromodomain-containing protein 4 inhibitors, Computed Properties of 30086-17-0, the main research area is imidazolylmethylquinolinol bromodomain containing protein 4 inhibitor; 8-OH-Quinoline; Anti-cancer activity; Bromodomain-containing protein 4; Computer-aided drug design; Early ADME/T evaluation; Rational hit-to-lead optimization.

Bromodomain-containing protein 4 (BRD4), an epigenetic reader of acetyl lysine, has emerged as a promising therapeutic target for many diseases including cancer, inflammation and heart failure. The previous study reported that nitroxoline, an FDA approved antibiotic, showed potential BRD4 inhibitory activity and antiproliferation activity against leukemia cell lines. In this study, the authors further explored the structure-activity relationship (SAR) around nitroxoline and employed the previously developed machine learning based activity scoring function BRD4LGR for further anal. To improve the cellular level activity, physico-chem. properties were optimized using computational approaches. Then the candidates were tested for their ADME/T profiles. Finally, based on this rational hit-to-lead optimization strategy, 3 drug-like BRD4 inhibitors were obtained, with different profiles on cell line selectivity for multiple myeloma, leukemia and triple neg. breast cancer. Further mechanism study showed these compounds could down-regulate c-Myc to inhibit cancer cell growth. This work illustrates the application of multiple computer-aided drug design techniques in a hit-to-lead optimization scenario, and provides novel potent BRD4 inhibitors with different phenotype propensities for future cancer treatment.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 30086-17-0 belongs to class imidazoles-derivatives, name is 5-Fluoro-1H-imidazole, and the molecular formula is C3H3FN2, Computed Properties of 30086-17-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Guo, Jing published the artcileDesign, synthesis, structure-activity relationships study and X-ray crystallography of 3-substituted-indolin-2-one-5-carboxamide derivatives as PAK4 inhibitors, Product Details of C10H7ClN2O, the main research area is indolinone preparation SAR docking PAK4 inhibitor crystal mol structure; Indolin-2-one; X-ray crystallography; p21-activated kinase 4.

We have previously described the identification of indolin-2-one-5-carboxamides as potent PAK4 inhibitors. This study expands the structure-activity relationships on our original series by presenting several modifications in the lead compounds, I and II. A series of novel derivatives was designed, synthesized, and evaluated in biochem. and cellular assay. Most of this series displayed nanomolar biochem. activity and potent antiproliferative activity against A549 and HCT116 cells. The representative compound III exhibited excellent enzyme inhibition (PAK4 IC50 = 25 nM) and cellular potency (A549 IC50 = 0.58 μM, HCT116 IC50 = 0.095 μM). An X-ray structure of compound III bound to PAK4 was obtained. Crystallog. anal. confirmed predictions from mol. modeling and helped refine SAR results. In addition, Compound III displayed focused multi-targeted kinase inhibition, good calculated drug-likeness properties. Further profiling of compound III revealed it showed weak inhibitory activity against various isoforms of human cytochrome P 450.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 62457-94-7 belongs to class imidazoles-derivatives, name is (4-Chlorophenyl)(1H-imidazol-2-yl)methanone, and the molecular formula is C10H7ClN2O, Product Details of C10H7ClN2O.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Alverez, Celeste N. published the artcileIdentification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1, Product Details of C11H10N2O2, the main research area is triazolo quinazolinone preparation anticancer drug discovery pharmacokinetic SAR.

As a mitotic-specific target widely deregulated in various human cancers, polo-like kinase 1 (Plk1) has been extensively explored for anticancer activity and drug discovery. Although multiple catalytic domain inhibitors were tested in preclin. and clin. studies, their efficacies are limited by dose-limiting cytotoxicity, mainly from off-target cross reactivity. The C-terminal noncatalytic polo-box domain (PBD) of Plk1 has emerged as an attractive target for generating new protein-protein interaction inhibitors. Here, we identified a 1-thioxo-2,4-dihydro-[1,2,4]triazolo[4,3-a]quinazolin-5(1H)-one scaffold that efficiently inhibits Plk1 PBD but not its related Plk2 and Plk3 PBDs. Structure-activity relationship studies led to multiple inhibitors having ≥10-fold higher inhibitory activity than the previously characterized Plk1 PBD-specific phosphopeptide, PLHSpT (Kd ~450 nM). In addition, S-Me prodrugs effectively inhibited mitotic progression and cell proliferation and their metabolic stability was determined These data describe a novel class of small-mol. inhibitors that offer a promising avenue for future drug discovery against Plk1-addicted cancers.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 94084-75-0 belongs to class imidazoles-derivatives, name is 4-((1H-Imidazol-1-yl)methyl)benzoic acid, and the molecular formula is C11H10N2O2, Product Details of C11H10N2O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Volynets, Galyna published the artcileIdentification of protein kinase fibroblast growth factor receptor 1 (FGFR1) inhibitors among the derivatives of 5-(5,6-dimethoxybenzimidazol-1-yl)-3-hydroxythiophene-2-carboxylic acid, Application of 5,6-Dimethoxy-1H-benzo[d]imidazole, the main research area is dimethoxy benzimidazolyl hydroxythiophene carboxylate preparation FGFR1 inhibitor cancer.

Abstract: Fibroblast growth factor receptor 1 (FGFR1) plays an important role in tumorigenesis, suggesting that inhibitors of this protein kinase may become important compounds for the development of anticancer agents. Using mol. docking approach, we have identified a novel class of FGFR1 inhibitors belonging to the derivatives of 5-(5,6-dimethoxybenzimidazol-1-yl)-3-hydroxythiophene-2-carboxylic acid. It was revealed that the most promising compound 5-(5,6-dimethoxybenzimidazol-1-yl)-3-[2-(methanesulfonyl)benzyloxy]thiophene-2-carboxylic acid Me ester inhibits FGFR1 with an IC50 value of 150 nM in in vitro kinase assay. The structure-activity relationships have been studied, and the binding mode of this chem. class has been proposed. Graphic abstract: [Figure not available: see fulltext.].

Monatshefte fuer Chemie published new progress about Antitumor agents. 72721-02-9 belongs to class imidazoles-derivatives, name is 5,6-Dimethoxy-1H-benzo[d]imidazole, and the molecular formula is C9H10N2O2, Application of 5,6-Dimethoxy-1H-benzo[d]imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Moustakim, Moses published the artcileDiscovery of an MLLT1/3 YEATS Domain Chemical Probe, SDS of cas: 94084-75-0, the main research area is MLLT1 YEATS domain chem probe; MLLT1; MLLT3; YEATS; chemical probes; epigenetics.

YEATS domain (YD) containing proteins are an emerging class of epigenetic targets in drug discovery. Dysregulation of these modified lysine-binding proteins has been linked to the onset and progression of cancers. We herein report the discovery and characterization of the first small-mol. chem. probe, SGC-iMLLT, for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent and selective inhibitor of MLLT1/3-histone interactions. Excellent selectivity over other human YD proteins (YEATS2/4) and bromodomains was observed Furthermore, our probe displays cellular target engagement of MLLT1 and MLLT3. The first small-mol. X-ray co-crystal structures with the MLLT1 YD are also reported. This first-in-class probe mol. can be used to understand MLLT1/3-associated biol. and the therapeutic potential of small-mol. YD inhibitors.

Angewandte Chemie, International Edition published new progress about Antitumor agents. 94084-75-0 belongs to class imidazoles-derivatives, name is 4-((1H-Imidazol-1-yl)methyl)benzoic acid, and the molecular formula is C11H10N2O2, SDS of cas: 94084-75-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zheng, Xiaozhang published the artcileStructure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors, Category: imidazoles-derivatives, the main research area is amide containing nicotinamide phosphoribosyltransferase inhibitor preparation cancer.

Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). A Nampt cocrystal structure was subsequently obtained and enabled the design of addnl. amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Addnl. modifications of these mols. afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MDCK permeability, plasma protein binding). An optimized compound was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model. Journal of Medicinal Chemistry published new progress about Antitumor agents. 588720-29-0 belongs to class imidazoles-derivatives, name is Imidazo[1,5-a]pyridine-7-carboxylic acid, and the molecular formula is C8H6N2O2, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Feng, Song published the artcileDiscovery of Imidazopyridine Derivatives as Highly Potent Respiratory Syncytial Virus Fusion Inhibitors, Synthetic Route of 67625-38-1, the main research area is imidazopyridine preparation antiviral respiratory syncytial virus fusion inhibitory activity; Respiratory syncytial virus (RSV); antiviral; fusion inhibitors; heterocycle; imidazopyridine; virus.

A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and phys.-chem. properties. Several highly potent compounds such as I (R = CONH2, SO2Me, SO2Et) were identified with single nanomolar activities. The most potent compound I (R = SO2Et) showed an IC50 of 3 nM, lower microsome clearance and no CYP inhibition. The profile of I (R = SO2Et) appeared to be superior to BMS433771, and supported further optimization.

ACS Medicinal Chemistry Letters published new progress about Antiviral agents. 67625-38-1 belongs to class imidazoles-derivatives, name is Ethyl 6-chloroimidazo[1,2-a]pyridine-2-carboxylate, and the molecular formula is C10H9ClN2O2, Synthetic Route of 67625-38-1.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Feng, Song published the artcileDiscovery of Imidazopyridine Derivatives as Highly Potent Respiratory Syncytial Virus Fusion Inhibitors, Quality Control of 82090-52-6, the main research area is imidazopyridine preparation antiviral respiratory syncytial virus fusion inhibitory activity; Respiratory syncytial virus (RSV); antiviral; fusion inhibitors; heterocycle; imidazopyridine; virus.

A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and phys.-chem. properties. Several highly potent compounds such as I (R = CONH2, SO2Me, SO2Et) were identified with single nanomolar activities. The most potent compound I (R = SO2Et) showed an IC50 of 3 nM, lower microsome clearance and no CYP inhibition. The profile of I (R = SO2Et) appeared to be superior to BMS433771, and supported further optimization.

ACS Medicinal Chemistry Letters published new progress about Antiviral agents. 82090-52-6 belongs to class imidazoles-derivatives, name is Imidazo[1,2-a]pyridin-2-ylmethanol, and the molecular formula is C8H8N2O, Quality Control of 82090-52-6.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem