Current Status of Novel Pyridine Fused Derivatives as Anticancer Agents: An Insight into Future Perspectives and Structure Activity Relationship (SAR)

Abstract

: Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease. Oxygen and nitrogen-based heterocyclic compounds have shown remarkable therapeutic activity towards several diseases, including cancer. In this review, we have attempted to summarize the work done in the last decade (2009-2019), highlighting the anticancer activity of pyrido fused five-membered heterocyclic ring derivatives. Additionally, we have focused on seven heterocyclic pyridine fused rings: Imidazopyridine, Triazolopyridine, Pyrrolopyridine, Pyrazolopyridines, Thienopyridine, and Isoxazolopyridine. A total of forty-nine compounds have been studied based on their in-vitro cytotoxic activity and their structure-activity relationship, underlining the anticancer activity of their various pharmacophores and substituents. This review, therefore, aims to draw the attention of the researchers worldwide towards the enormous scope of development of heterocyclic drug compounds, focussing mainly on pyrido fused five-membered heterocyclic rings as anticancer drugs.

Six‐Membered Aromatic Nitrogen Heterocyclic Anti‐Tumor Agents: Synthesis and Applications

“…Due to electron‐withdrawing power of the nitrogen atoms within the ring, there is decreased electron cloud density at positions 2, 4, and 6 compared to positions 3 and 5. In acidic environments, electrophilic substitution reactions predominantly occur at positions 3 and 5, while nucleophilic reactions such as amination, alkylation, arylation, and acylation primarily occur at positions 2, 4, and 6 [11–13] …”

“…In acidic environments, electrophilic substitution reactions predominantly occur at positions 3 and 5, while nucleophilic reactions such as amination, alkylation, arylation, and acylation primarily occur at positions 2, 4, and 6. [11][12][13] Additionally, pyridine is the second most commonly employed nitrogen heterocycle in all pharmaceuticals approved by the FDA in the United States, and it holds the highest rank among aromatic compounds. Examination of substitution patterns in these pyridine-based drugs reveals a preference for the C2-position, followed by the C3-position.…”

Electrosynthesis of Highly Functionalized Polycyclic N-Heteroaromatics through Cascade Radical Cyclization and Alkoxylation in Batch and Continuous-Flow

“…Polycyclic N-heteroaromatics (PNAs) including pyridine-fused molecules are prevalent in biologically active compounds, pharmaceuticals, and functional materials, − especially the supercapacitors , and photoelectrodes , of photoelectron-chemical cells (Scheme a). In general, multistep prefunctionalization including halogenation, condensation, addition, oxidation and final coupling, and cyclization is usually inevitable to construct the PNAs. − In contrast, the more straightforward and powerful method for building highly functionalized polycyclic aromatic compounds (PAs) was developed via a one-pot multistep cascade cyclization − or transition-metal-catalyzed annulative π-extension. − In general, attack of the radical or transition metal at the corresponding π system mediated the cascade processes to construct the desired PAs.…”

Synthesis of 1-Amino-3-oxo-2,7-naphthyridines via Smiles Rearrangement: A New Approach in the Field of Chemistry of Heterocyclic Compounds

“…Furthermore, it is well known that fused derivatives of furo[2,3- b ]pyridine show high biological activity [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Along this line we have previously synthesized several condensed furo[2,3- b ]pyridines based on the cyclopenta[ c ]pyridines, 5,6,7,8-tetrahydroisoquinolines and pyrano[3,4- c ]pyridines, obtaining compounds with neurotropic [ 25 , 26 ], antimicrobial [ 27 ], antitumor [ 28 ] and potent antiviral [ 29 ] activities.…”