Design and Synthesis of Novel Imidazopyridine Analogues and Evaluation as H+/K+-ATPase Antagonist

Abstract

CID data base were explored considering AZD0865 as standard and docked in proton pump ATPase pocket (PDB ID: 4ux2) to find out novel imidazopyridine derivatives as proton pump inhibitors. A number of compounds showed good proton pump ATPase inhibitory activity as per the molecular docking study as compared to standard compound AZD0865. The compound AZD0865showed a docking score of -7.11 and revealed the interactions with amino acids Asn 138 and Asp 137. A series of novel imidazopyridine derivatives as proton pump inhibitors were docked, synthesized and characterized by IR, NMR, CHN and MS spectral analysis. The target imidazopyridines were prepared from the intermediate substituted 2-aminonicotinic acid and 2-bromo-1-substituted ethanone. in vitro pharmacological studies explained that some compounds exhibited moderate to good proton pump ATPase inhibitory activity in comparison with the reference drugs i.e. AZD0865. Compound N-(3-(aminomethyl)benzyl)-3-(benzylamino)-2-(o-tolyl)imidazo[1,2-a]pyridine-8-carboxamide and N-(3-(aminomethyl)benzyl)-3-(benzylamino)-2-(4-ethylphenyl)imidazo[1,2-a]pyridine-8-carboxamide showed higher activities with the IC50 6.2 and 6.0 μg. Many compounds showed IC50 as weak antiulcer activity as compared to positive control AZD0865.

Recent Advances in the Synthesis of Imidazo[1,2‐a]pyridines: A Brief Review

“…This review also clearly picturized the unfocussive methodologies like microwave irradiation, photocatalytic and heteroannular type reactions. A number of newer synthetic methods for the synthesis of imidazo [1,2-a]pyridines are based on the combination of several interesting new molecular scaffolds such as benzonitrile, 3-phenyl- [1,2,3]triazolo [1,5-a]pyridine, 3-formylchromone, isocyanides, substituted N-propargyl imidazole and substituted cyclic amine, azaarenes, malonitrile, N-(2pyridinyl)enaminones, ethyl-containing tertiary amines, etc.…”

“…During the past two decades, imidazo[1,2‐ a ]pyridines have been featured as one of the utmost versatile building blocks and gained much interest in synthetic organic chemistry due to its wide range of biological activities such as antiulcer, [1] anticonvulsant, [2] antifungal, [3] antiviral, [4] anticancer, [5] antiprotozoal, [6] antibacterial, [7] anti‐inflammatory, [2] anthelmintic, [8] analgesic, [9] antituberculosis, [10] antipyretic, [2] antiepileptic, [11] and antitumor activities [12] . A wide range of medications such as Zolpidem ( 1 , used in the treatment of insomnia), Zolimidine ( 2 , used for the treatment of peptic ulcer), Olprinone ( 4 , for the treatment of acute heart failure), Necopidem and Saripidem ( 5 and 3 , both works as an anxiolytic agent), Microprofen ( 6 , Prostanoid signaling modulators, Analgesic and NSAID), etc.…”

C(sp2)‐H Imination of Imidazo[1,2‐a]pyridines: A Catalyst‐Free, Multicomponent Approach

“…Imidazo[1,2‐ a ]pyridines are bicyclic dinitrogen‐containing privileged scaffolds that have received long‐lasting attention from synthetic and medicinal chemists due to their rich natural abundance and their spectrum of biological activities [1–3] . For example, imidazo[1,2‐ a ]pyridine derivatives exhibit, antiulcer, [2a] anticonvulsant, [2b] antifungal, [2c] antiviral, [2d] anticancer, [2e] antiprotozoal, [2f] antibacterial, [3a] anti‐inflammatory, [2b] anthelmintic, [3b] analgesic, [3c] antitubercular, [3d] antipyretic, [2b] antiepileptic, [3e] and antitumor activities [3f] . Besides, there are several drugs such as zolpidem, [4] alpidem, [4] olprinone, [5] zolimidine, [6] necopidem and saripidem, [7] and rifaximin [8] that contains the imidazo[1,2‐a]pyridine moiety (Figure 1).…”

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

“…Imidazo[1,2- a ]pyridine is a privileged structure that plays an important role in organic synthesis and in the pharmaceutical industry. This scaffold is present in drugs with several biological activities, such as antiviral [ 1 ], anticonvulsant [ 2 ], antibacterial [ 3 ], antipyretic [ 4 ], antituberculosis [ 5 ], anticancer [ 6 ], anthelmintic [ 5 ], antifungal [ 7 ], analgesic [ 8 ], antiulcer [ 9 ], antiprotozoal [ 10 ], antitumor [ 11 ], and anti-inflammatory [ 12 ]. Examples of commercial drugs are depicted in Figure 1 [ 13 ] and include alpidem (anxiety disorders), minodronic acid (osteoporosis), miroprofen (non-steroidal anti-inflammatory drug, NSAID), necopidem (insomnia), olprinone (acute heart failure), saripidem (type A GABA receptor agonist), zolimidine (gastroesophageal reflux disease), and zolpidem (insomnia).…”