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Review
. 2022 May 20;12(24):15385-15406.
doi: 10.1039/d2ra01571d. eCollection 2022 May 17.

Pyridine: the scaffolds with significant clinical diversity

Sourav De  1 , Ashok Kumar S K  2 , Suraj Kumar Shah  1 , Sabnaz Kazi  1 , Nandan Sarkar  1 , Subhasis Banerjee  3 , Sanjay Dey  1
Affiliations
Review

Pyridine: the scaffolds with significant clinical diversity

Sourav De et al. RSC Adv. .

Abstract

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research. This privileged scaffold has been consistently incorporated in a diverse range of drug candidates approved by the FDA (Food and Drug Administration). This moiety has attracted increasing attention from several disease states owing to its ease of parallelization and testing potential pertaining to the chemical space. In the next few years, a larger share of novel pyridine-based drug candidates is expected. This review unifies the current advances in novel pyridine-based molecular frameworks and their unique clinical relevance as reported over the last two decades. It highlights an inclination to the use of pyridine-based molecules in drug crafting and the subsequent emergence of several potent and eligible candidates against a range of diversified diseases.

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Conflict of interest statement

The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this study.

Figures

Fig. 1
Fig. 1. Examples of naturally occurring pyridine derivatives.
Scheme 1
Scheme 1. Synthesis of substituted pyridines by a condensation method.
Scheme 2
Scheme 2. [2 + 2 + 1 + 1] multicomponent synthesis of pyridine derivatives.
Scheme 3
Scheme 3. A one-pot synthesis of substituted pyridines from 1,3-dicarbonyl and vinylogous amide.
Scheme 4
Scheme 4. Synthesis of pyridine derivatives via the aza-Diels–Alder method.
Scheme 5
Scheme 5. The [4 + 2] rhodium-mediated synthesis of pyridines.
Scheme 6
Scheme 6. [2 + 2 + 2] cobalt-mediated synthesis of substituted pyridines. Cbz = carbobenzyloxy, Cod = cyclooctadiene.
Fig. 2
Fig. 2. Some examples of most anti-bacterial agent of substituted pyridines.
Scheme 7
Scheme 7. Synthesis of most active antiviral agent chalcone conjugate with malonate and pyridine.
Fig. 3
Fig. 3. Representative examples of antiviral activity of compounds containing pyridine as the basic unit.
Fig. 4
Fig. 4. Representative examples of the most active anticancer agents.
Scheme 8
Scheme 8. Reagents and conditions for synthesizing of most active anticancer agent pyridine-ureas 35a–n; (i) DMF-DMA, xylene, reflux 7 h; (ii) NH4OAc, AcOH, reflux 4 h; (iii) methanol, NH2NH2·H2O, reflux 2 h; (iv) NaNO2, AcOH, stirring 2 h; (v) xylene, reflux 1 h; (vi) xylene, reflux 3 h.
Scheme 9
Scheme 9. Synthesis of curcumin-inspired imidazo[1,2-a]pyridine analogues 36a–t; reagents and conditions: (i) 15% NaOH, ethanol, 0 °C – rt, 2–3 h, 71–85%. (ii) Ethanol, reflux, 1 h, 74.3%; (iii) NIS, rt, 1 h, 65.1%; (iv) Pd(PPh3)4, Na2CO3, dioxane : H2O = 8 : 2, 75 °C, 2–6 h, 65–73%; (v) LiAlH4, THF, 0 °C – rt, 1 h, 67–71%; (vi) DMP, DCM, 0 °C, 1 h, 65–74%; (vii) CH3ONa, ethanol, rt, 15 min, 63–82%.
Fig. 5
Fig. 5. Most active anticancer agent curcumin conjugated imidazo[1,2-a]pyridine derivatives.
Scheme 10
Scheme 10. Synthesis of most active anticancer agent dipyridinyl-thiazole sugar and acrylidine derivatives.
Scheme 11
Scheme 11. Synthesis of most active anticancer agent heteroaryl-substituted pyridine glycosides.
Scheme 12
Scheme 12. Synthesis of most active anticancer agent pyridinyl furan sugar derivatives.
Fig. 6
Fig. 6. Synthesis of most active anticancer agent pyridine derivatives.
Scheme 13
Scheme 13. Synthesis of most active anticancer agent amide derivatives of imidazopyridine.
Fig. 7
Fig. 7. Most active anticancer agent 6-di-[2-(heteroaryl)vinyl]pyridines.
Scheme 14
Scheme 14. Synthesis of 3-amino-5H-chromeno[4,3-b]pyridine-5-ones derivatives.
Fig. 8
Fig. 8. Most active anticancer agentImidazol pyridine and bipyridine derivatives.
Fig. 9
Fig. 9. In vitro yeast α-glucosidase inhibition activity with IC50 values.
Fig. 10
Fig. 10. Most active anticancer agent thieno[2,3-b]pyridine derivatives.
Fig. 11
Fig. 11. Most active antifungal agent pyridine derivatives.
Fig. 12
Fig. 12. Quaternized pyridine derivatives of betulin triterpenes demonstrate antibacterial and antifungal activities.
Fig. 13
Fig. 13. Structures of 2/4-acetyl pyridine connected to imidazo[1,2-a]pyridines.
Fig. 14
Fig. 14. Structure of pyridines Moiety for antimicrobial.
Fig. 15
Fig. 15. Structure of 4-benzylsulfanylpyridine-2-carbohydrazides.
Fig. 16
Fig. 16. Synthesis of 1H-pyrazolo [3,4-b]pyridine analogues.
Fig. 17
Fig. 17. Synthesis of thiazolo pyridine.
Fig. 18
Fig. 18. Structures of pyridine compounds for various pharmacological evaluation.
Fig. 19
Fig. 19. Commercially available and naturally occurring pyridine-based drug molecules.
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