Synthesis and analgesic‐antiinflammatory activities of ethyl 2‐[3‐(1‐phenoxy(methoxy)carbonyl‐4‐aryl‐(alkyl)‐1,4‐dihydropyridyl)]acetates

Abstract

Reaction of ethyl 2‐(3‐pyridyl)acetate 4a or ethyl 2‐methyl‐2‐(3‐pyridyl)acetate 4b, with phenyl chloroformate or methyl chloroform ate, afforded the intermediate pyridinium salt 5 which undergoes regioselective nucleophilic attack at C‐4 upon reaction with a Grignard reagent in the presence of a cuprous iodide catalyst at −23° to yield the corresponding ethyl 2‐[3‐(1‐phenoxy(methoxy)carbonyl‐4‐aryl(alkyl)‐1,4‐dihydropyridyl)]acetates 6a‐f in 64–96% chemical yield. No product arising from reaction of the ester substituent of the pyridinium salt 5 with the Grignard reagent was observed. The 1H nmr spectra of 6a‐f exhibited dual resonances for the 1,4‐dihydropyridyl H‐2, H‐5 and H‐6 protons at 25° in deuteriochloroform. These dual resonaces were attributed to two different rotameric configurations resulting from restricted rotation about the nitrogen‐to‐carbonyl carbamate bond due to its double bond character. Compound 6 generally exhibited superior analgesic and antiinflammatory activities, compared to the reference drugs aspirin and ibuprofen, respectively. These structure‐activity correlations indicate the 1,4‐dihydropyridyl ring system present in 6 is a suitable bioisostere for the aryl (heteroaryl) ring present in aryl(heteroaryl)acetic acid non‐steroidal antiinflammatory drugs.

Ultrasound and Nano‐Catalysts: An Ideal and Sustainable Combination to Carry out Diverse Organic Transformations

“…1,4‐Dihydropyridine and related derivatives are found to possess significant pharmacological efficacies that include anti‐tumor, anti‐tubercular, anti‐thrombotic, anti‐inflammatory etc activities. Abaszadeh et al .…”

Nanosized MgO as a Heterogeneous Base Catalysts, Catalyses Multicomponent Reaction of Cyclic Enaminoketones, Malononitrile, and Aromatic Aldehydes

“…[2] As previously documented, among these biologically active compounds 1,4-dihydropyridines and imidazo [1,2-a]quinolines are particularly well known for their therapeutic applications. [3] Dihydropyridines were reported for their antitumor, [4] calcium channel blokers, [5] antitubercular, [6] analgesic, [7] antithrombotic, [8] anti-inflammatory, [9] anticonvulsant [10] and other pharmacological activities. Some of the marketed drug preparation containing 1,4-dihydropyridine moieties are Nifedipine, Amlodipine, Oxodipine, etc.…”

Evaluation of magnetically recyclable nano-Fe3O4 as a green catalyst for the synthesis of mono- and bis-tetrahydro-4H-chromene and mono and bis 1,4-dihydropyridine derivatives

“…Due to being pharmacologically active and acting as antitumor [23], calcium channel blocker [24], antitubercular [25], analgesic [26], antithrombotic [27], anti-inflammatory [28], anticonvulsant agents [29], they are of many interests.…”