Bioactive 2-pyridone-containing heterocycle syntheses using multicomponent reactions

Abstract

This review provides a comprehensive overview of multicomponent reactions (MCRs) for the synthesis of biologically active 2-pyridone-containing heterocycles.

Achiral 2‐pyridone and 4‐aminopyridine act as chiral inducers of asymmetric autocatalysis with amplification of enantiomeric excess via the formation of chiral crystals

“…2-Pyridone 3 is an achiral planar heterocyclic compound that serves as a key structural motif in a variety of bioactive compounds. 70 Among the selected examples of drugs approved by FDA containing 2-pyridone core without any chiral stereogenic center, 71 Pirfenidone crystallizes in a chiral space group of P2 1 . 72 In a strict manner, the rate of solubilization may vary between enantiomeric chiral crystals under life's chiral circumstances due to potential diastereomeric interactions between enantiomorphic crystals and the homochirality observed in life.…”

“…2‐Pyridone 3 is an achiral planar heterocyclic compound that serves as a key structural motif in a variety of bioactive compounds 70 . Among the selected examples of drugs approved by FDA containing 2‐pyridone core without any chiral stereogenic center, 71 Pirfenidone crystallizes in a chiral space group of P 2 1 72 .…”

Design and Synthesis of Novel 1‐((1‐Phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)pyridin‐2(1H)‐one Derivatives

“…[19] Several review articles have focused on this class of compounds because of their medicinal applications. [20][21][22] 2-Hydroxypyridine (1) can be tautomerized to 2-pyridinone (2) and the keto form of the heterocyclic ring tends to dominate in both solid and solution phases, even though this can be influenced by the electronic properties of substituents attached to the ring (Scheme 1). [21] In drug discovery, 2-pyridinone derivatives have gained significant attention due to the increasing number of FDA-approved drugs such as Gimeracil, [23] Pirfenidone, [24] Doravirine [25] and Ciclopirox [26] (Figure 1).…”

“…Pyridinones have also attracted significant interest from researchers due to their crucial biological activities, such as antibacterial, [15] anti‐inflammatory, [16] anti‐hepatitis B virus, [17] SARS‐CoV‐2 main protease inhibitor [18] and anticancer [19] . Several review articles have focused on this class of compounds because of their medicinal applications [20–22] . 2‐Hydroxypyridine ( 1 ) can be tautomerized to 2‐pyridinone ( 2 ) and the keto form of the heterocyclic ring tends to dominate in both solid and solution phases, even though this can be influenced by the electronic properties of substituents attached to the ring (Scheme 1).…”

P(NMe2)3-Mediated Regioselective N-Alkylation of 2-Pyridones via Direct Deoxygenation of α-Keto Esters

“…N-Alkylated 2-pyridones are important subunits in natural products and pharmaceutical molecules . Extensive efforts have been dedicated to the synthesis of N-substituted 2-pyridones, including the construction of 2-pyridone cycles and the N-functionalization of 2-pyridone skeletons, the latter of which is usually considered as a more straightforward and efficient approach . However, the existence of tautomerism between 2-pyridone and 2-hydroxypyridine easily causes an ambident nucleophilic property, resulting in the inevitable difficulty of the regioselective N- over O-alkylation of 2-pyridone (Scheme a) .…”