Diethylaminosulfur Trifluoride: A Novel, Low-Cost, Stable Double Thiolation Reagent for Imidazo[1,2-α]pyridines
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ABSTRACT:
SUBMITTER: Jiang H
PROVIDER: S-EPMC8515576 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:New conformationally extended dipeptide surrogates based on an imidazo[1,2-a]pyridine scaffold are described. Efficient synthesis and incorporation into host peptides affords structures with native side-chain functionality and hydrogen bonding elements on one face of the backbone. Structural analysis by NMR suggests that model peptidomimetics adopt a ?-strand-like conformation in solution.
| S-EPMC3528799 | biostudies-literature
Project description:A novel metal catalyst-free and environmentally friendly method for the regioselective iodination of imidazo[1,2-α]pyridines at their C3 position is disclosed, which has a wide substrate scope and could be sustainable. This reaction proceeds through ultrasound acceleration in the presence of a green alcohol solvent. Compared with a conventional heating system, the reaction efficiency and the rate are significantly improved and the iodine atom economy is maximized using ultrasound techniques.
| S-EPMC8515396 | biostudies-literature
Project description:A series of imidazo[1,2-a]pyridines which directly bind to HCV Non-Structural Protein 4B (NS4B) is described. This series demonstrates potent in vitro inhibition of HCV replication (EC50 < 10 nM), direct binding to purified NS4B protein (IC50 < 20 nM), and an HCV resistance pattern associated with NS4B (H94N/R, V105L/M, F98L) that are unique among reported HCV clinical assets, suggestive of the potential for additive or synergistic combination with other small molecule inhibitors of HCV replication.
| S-EPMC4025644 | biostudies-literature
Project description:An efficient three-component one-pot and operationally simple cascade of 2-aminopyridines with sulfonyl azides and terminal ynones is reported, providing a variety of polysubstituted imidazo[1,2-a]pyridine derivatives in moderate to excellent yields. In particular, the reaction goes a through CuAAC/ring-cleavage process and forms a highly active intermediate α-acyl-N-sulfonyl ketenimine with base free.
| S-EPMC9280286 | biostudies-literature
Project description:Background?-Bromination of the side chain of aromatic ketones using NBS in the presence of p-toluenesulfonic acid (p-TsOH) in acetonitrile is very common. However, regioselective bromination of bis and tris(?-bromoacetophenones) with NBS in the presence of p-TsOH in acetonitrile under microwave irradiation is quite novel. The bis- and tris(?-bromoacetophenones) are used in synthesis of bis and tris(heterocycles). bis(heterocycles) have received a great deal of attention, because many biologically active natural and synthetic products have molecular symmetry. The use of the pressurized microwave irradiation is very advantageous to many syntheses and provide a large rate enhancement.ResultsBis and tris(?-bromoacetophenones) were obtained as single monobrominated derivatives in a shorter time than the conventional conditions. The results clearly demonstrate the better reactivity and selectivity of NBS/p-TsOH/CH3CN as a brominating mixture under microwave conditions. The reaction of bis and tris(?-bromoacetophenone) with 2-aminopyridine and 2-aminopyrimidine proceeded smoothly in a mixture of anhydrous ethanol and DMF under reflux or using 300 W/105°C/ 20 min microwave irradiation conditions to afford the corresponding bis(imidazo[1,2-a]pyridine), bis(imidazo[1,2-a]pyrimidine) and tris(imidazo[1,2-a]pyridine) derivatives in moderate to excellent yields. The carbonyl analogue of the targeted bis(imidazopyridines) could be synthesized by the reaction of N,N-dimethyl-N'-(pyridin-2-yl)formimidamide with bis(?-bromoacetophenone) in refluxing ethanol. The structures of the newly synthesized compounds were confirmed by their spectral data as well as their elemental analyses.ConclusionIn conclusion, selective ?-bromination of bis- and tris(acetophenones) has been accomplished efficiently utilizing NBS/p-TsOH/CH3CN under microwave irradiation. In addition, a facile synthesis of novel series of bis- and tris(imidazopyridine) and bis(imidazopyrimidine) derivatives.
| S-EPMC3698004 | biostudies-literature
Project description:A novel three-component reaction has been developed to assemble biologically and pharmaceutically important tetracyclic fused imidazo[1,2-a]pyridines in a one-pot fashion utilizing readily available 2-aminopyridines, isatins and isocyanides. The three-component coupling proceeds through the Groebke-Blackburn-Bienaymé reaction followed by a retro-aza-ene reaction and subsequent nucleophilic reaction of the in-situ generated imidazo[1,2-a]pyridines bearing an isocyanate functional group.
| S-EPMC4979633 | biostudies-literature
Project description:A facile access to 3-heterosubstituted (3-oxazolidinonyl/indolyl/phenoxy) imidazo[1,2-a]pyridines from readily available 2-aminopyridines and electron-rich (internally activated) alkynes like ynamides/ynamines/ynol ethers is achieved via Cu(OTf)2-mediated intermolecular diamination under aerobic conditions. The reaction is highly regioselective, owing to internal electron bias, and thus led to a single regioisomer with heterosubstitution at C3.
| S-EPMC6641143 | biostudies-literature
Project description:The in silico construction of a PDGFR? kinase homology model and ensuing medicinal chemistry guided by molecular modeling, led to the identification of potent, small molecule inhibitors of PDGFR. Subsequent exploration of structure-activity relationships (SAR) led to the incorporation of a constrained secondary amine to enhance selectivity. Further refinements led to the integration of a fluorine substituted piperidine, which resulted in significant reduction of P-glycoprotein (Pgp) mediated efflux and improved bioavailability. Compound 28 displayed oral exposure in rodents and had a pronounced effect in a pharmacokinetic-pharmacodynamic (PKPD) assay.
| S-EPMC4027622 | biostudies-literature
Project description:BackgroundThe proton at position 5 of imidazo[1,2-a]pyridines substituted with an angular electron withdrawing group (EWG) at position 3, shows an unusual downfield chemical shift, which is usually explained in terms of a peri effect. However usage of this term is sometimes confusing. In this investigation, it is proposed that the aforementioned shift is in fact a combination of several factors: Anisotropy, long-distance mesomerism and an attractive intramolecular interaction of the electrostatic hydrogen bond type.ResultsTheoretical calculations were performed aimed to obtain evidence of the existence of an intramolecular non-bonding interaction between H-5 and the oxygen atom of the EWG. Results derived from conformational and vibrational analysis at the DFT B3LYP/6-311++G(d,p) level of theory, the determination of Bond Critical Points derived from AIM theory, and the measurement of some geometrical parameters, support the hypothesis that the higher stability of the prevailing conformation in these molecules (that in which the oxygen of the EWG is oriented towards H-5) has its origin in an intramolecular interaction.ConclusionComputational calculations predicted correctly the conformational preferences in angular 3-?-EWG-substituted imidazo[1,2-a]pyridines. The existence of an electrostatic hydrogen bond between H-5 and the oxygen atom of the ?-EWG was supported by several parameters, including X-ray crystallography. The existence of such structural array evidently impacts the H-5 chemical shift.
| S-EPMC3663774 | biostudies-literature
Project description:The use of epigenetic bromodomain inhibitors as anticancer therapeutics has transitioned from targeting bromodomain extraterminal domain (BET) proteins into targeting non-BET bromodomains. The two most relevant non-BET bromodomain oncology targets are cyclic AMP response element-binding protein (CBP) and E1A binding protein P300 (EP300). To explore the growing CBP/EP300 interest, we developed a highly efficient two-step synthetic route for dimethylisoxazole-attached imidazo[1,2-a]pyridine scaffold-containing inhibitors. Our efficient two-step reactions enabled high-throughput synthesis of compounds designed by molecular modeling, which together with structure-activity relationship (SAR) studies facilitated an overarching understanding of selective targeting of CBP/EP300 over non-BET bromodomains. This led to the identification of a new potent and selective CBP/EP300 bromodomain inhibitor, UMB298 (compound 23, CBP IC50 72 nM and bromodomain 4, BRD4 IC50 5193 nM). The SAR we established is in good agreement with literature-reported CBP inhibitors, such as CBP30, and demonstrates the advantage of utilizing our two-step approach for inhibitor development of other bromodomains.
| S-EPMC8856734 | biostudies-literature