AlCl3-mediated hydroarylation–heteroarylation in a single pot: a direct access to densely functionalized olefins of pharmacological interest

Abstract

An unprecedented AlCl3-mediated method has been developed involving aromatic C-H bond addition to an alkyne and heteroarylation of an arene in a single pot leading to densely functionalized novel olefins, e.g. 2-(2,2-diarylvinyl)-3-arylquinoxalines, as potential inhibitors of sirtuins.

Exploring the gyrase ATPase domain for tailoring newer anti-tubercular drugs: Hit to lead optimization of a novel class of thiazole inhibitors

“…All these modification resulted in very potent molecules as shown in Tables 2, 3 and 4. The N-benzyl amino (26)(27)(28)(29)(30), carboxamide (31)(32)(33)(34)(35) was well accommodated as the right hand core than their corresponding sulphonamide analogues (36- A structural insight into the interaction profile of the most potent compound inhibitor from the study compound 27 (Figure 4) showed the molecule to be involved in polar contact with Asn52, a crucial residue of gyrB. Additionally, a cation-π interaction was also observed between the amino group of Arg82 and thiazole of compound.…”

“…The potent inhibitors from our study were also evaluated for their cardio toxicity profile in a zebra fish model using a previously reported protocol. 22,[32][33][34][35] Among the tested leads, compound 27, 31 and 36 were found to be completely devoid of cardio toxicity ( Figure 6) until 30µM the highest dose tested. Compound 12 though completely safe at lower concentration (until 10µM), while it displayed slight heart rate variability at 30µM.…”

“…Later, various N-benzyl/phenyl amino (26)(27)(28)(29)(30), carboxamide (31)(32)(33)(34)(35) and sulphonamide derivatives (36)(37)(38)(39)(40) were also explored as the right hand partner to have a clear profiling of the structure activity relationship. All these modification resulted in very potent molecules as shown in Tables 2, 3 and 4.…”

“…In a similar fashion, the thiourea (11-17 and 22-25) and the sulphonamide derivatives (36-40) were assembled from the 1-(5-nitrothiazol-2-yl)piperidin-4-amine scaffold (3) by reacting with their corresponding isothiocyante and sulphonyl chloride respectively. The amide derivatives (31)(32)(33)(34)(35) were developed by coupling the scaffold derivative (3) with the respective acid using propyl phosphonic anhydride as the coupling agent. Finally reductive amination of 1-(5-nitrothiazol-2-yl)piperidin-4-amine with desired aldehydes gave the designed amino derivatives (26)(27)(28)(29).…”

Design and synthesis of novel quinoline–aminopiperidine hybrid analogues as Mycobacterium tuberculosis DNA gyraseB inhibitors

“…Two potent compounds (45 and 47) from our study were subjected to hERG channel inhibition in a zebra fish model using a previously reported protocol. [26][27][28] Both the compounds were analyzed with heart rate variations and AV ratio and the compound 45 was found to be safe but compound 47 at 30 lM was found to be lethal to the embryos and lower concentrations (10 lM, 3 lM, 1 lM) did not had any major cardio toxicity when compared to positive control (20 lM Terfenadine) as shown in Figures 9a and 9b. Statistical analysis was done using GraphPad Prism Ò software applying one way ANOVA and Dunnet's posttest.…”