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.

Keywords:

• nitrogen heterocycles
• pharmaceuticals
• bioactive compounds
• current trend
• substituent effect

Acknowledgments

The authors acknowledge grant GZYYGJ2020023 from the Sino-Pakistan Cooperation Center on Traditional Chinese Medicine, located at the International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. Thanks are also due to The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China and HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi.

Abbreviations

AChE, acetylcholinesterase; COX, cyclooxygenase; DHP, dihydropyridine; FDA, Food and Drug Administration; GABA, γ-aminobutyric acid; GAK, G-associated kinase; HepG2, Hepatocellular carcinoma; MDR, multidrug-resistant; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; NAD, nicotinamide adenine dinucleotide; NADP, NAD phosphate; NO, nitric oxide; NSAIDs, nonsteroidal anti-inflammatory drugs; PDE, phosphodiesterase; PL, phospholipid-lowering; ROS, reactive oxygen species.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data, took part in drafting the article or revising it critically for important intellectual content, agreed to submit to the current journal, gave final approval to the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.