The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

Abstract

Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.

1,4-Dihydropyridine as a Promising Scaffold for Novel Antimicrobials Against Helicobacter pylori

“…1,4-DHP is one of the most privileged heterocyclic scaffolds in medicinal chemistry covering a broad spectrum of biological activities and therapeutic effects including antihypertensive, antianginal, neuroprotective, antioxidant, anti-inflammatory, anticancer, and antimicrobial ( Ioan et al, 2011 ; Carosati et al, 2012 ; Mishra et al, 2019 ; Ling et al, 2021 ). Most 1,4-DHP derivatives share some structural features, such as the unsaturated 1,4-DHP core ring with unsubstituted N1 atom, small alkyl groups (usually methyl) at the C2 and C6 positions, ester groups at the C3 and C5 positions, and a phenyl ring with different substituent types and patterns at the C4 position ( Olejnikova et al, 2014 ; Ling et al, 2021 ).…”

Pyridine Compounds with Antimicrobial and Antiviral Activities

“…An important role of pyridine is that it is used as an organic solvent or as ligand for coordination complexes [ 4 , 5 , 6 , 7 , 8 ]. The pyridine nucleus is found in many natural products, such as vitamins, alkaloids and coenzymes, as well as in many drugs ( Figure 1 ) and pesticides [ 9 , 10 ]. The recent literature mentions various series of compounds containing the pyridine nucleus, as a unique heterocycle, and with other heterocycles or fused with other heterocycles, which have remarkable antibacterial, antifungal and antiviral properties [ 1 , 9 , 10 , 11 , 12 , 13 ].…”

“…The pyridine nucleus is found in many natural products, such as vitamins, alkaloids and coenzymes, as well as in many drugs ( Figure 1 ) and pesticides [ 9 , 10 ]. The recent literature mentions various series of compounds containing the pyridine nucleus, as a unique heterocycle, and with other heterocycles or fused with other heterocycles, which have remarkable antibacterial, antifungal and antiviral properties [ 1 , 9 , 10 , 11 , 12 , 13 ]. The presence of an additional heterocycle compared to the pyridine one in the bioactive molecule proved to be beneficial in the sense that it intensified the therapeutic properties of the antimicrobial and antiviral ones, and also widened their range [ 3 , 4 , 5 , 6 , 7 , 8 ].…”

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

“…Pyridine moieties are present in many natural products, drugs, pesticides and industrial materials. Pyridine fragments are used in drugs due to their specific characteristics such as basicity, hydrogen bond forming ability, water solubility, and especially because of pyridine rings are bioisosteres of amines, amides, N-heterocyclic rings and benzene rings [1][2][3][4][5]. A special type of pyridine, the 4-pyridones, is also fairly well represented among drugs [5][6][7][8][9][10][11][12].…”