Nitropyridines in the Synthesis of Bioactive Molecules

Abstract

Pyridines are one of the most important and promising classes of N-heterocycles actively studied in modern organic and medicinal chemistry; in particular, pyridine is a privileged structural motif in drug design. From a synthetic organic chemistry perspective, nitropyridines can be considered as convenient and readily available precursors for a wide range of mono- and polynuclear heterocyclic systems demonstrating diverse activities, such as antitumor, antiviral, anti-neurodegenerative, etc. This review is an analysis of the literature on the use of nitropyridines for the synthesis of biologically active compounds, covering the period from 2015 to the present.

Keywords: biological activity; coordination compounds; heterocycles; nitro group; nitropyridines; radiolabeled compounds.

Scheme 1

Synthesis of potent JAK2 inhibitors 4 and 6. Data from [20].

Scheme 2

Bussiere’s method for the synthesis of GSK3 inhibitors 10 [21].

Scheme 3

Synthesis of potent kinase p70S6Kβ inhibitor 13. Adopted from [22].

Scheme 4

A method for the synthesis of 4-aza-6-nitrobenzofuroxan 16 [24].

Scheme 5

Synthesis of nitropyridine-containing potential urease inhibitors 19. Data from [25].

Scheme 6

Synthesis of novel urease inhibitors 20. Data from [26].

Scheme 7

S_N^H alkylamination of 3-nitroquinoline 22. Data from [33].

Scheme 8

Synthesis of antibacterial 3-nitropyridines [34].

Scheme 9

Preparation of epoxybenzooxocino[4,3-b]pyridine derivatives. Data from [35].

Scheme 10

Synthesis of 3,5-dinitropyrydine containing fluorophores [36,37,38].

Scheme 11

Synthesis of nitropyridine-based compounds with antimalarial activity. Data from [39].

Scheme 12

Synthesis of nitropyridine-linked 4-arylidenethiazolidin-4-ones 35. Data from [40].

Scheme 13

Synthesis of novel imidazo[4,5-b]pyridines [41].

Scheme 14

Synthesis of nitropyridine-containing herbicides. Data from [42].

Scheme 15

Synthesis of pyridyloxy-substituted acetophenone oxime ethers 44. Data from [43].

Scheme 16

Nitropyridine insecticides [44].

Scheme 17

Synthesis of pyridine-chromene ligand 47 and its metal complexes. Data from [45].

Scheme 18

Synthesis of pyridine-chromene ligand 47 and its metal complexes [46].

Scheme 19

Synthesis of copper and zinc complexes 51 with (5-nitropyridin-2-yl)imine ligands. Adopted from [47].

Scheme 20

Synthesis of the Ru-arene-dinitropyridinylmethylene complex. Data from [48].

Scheme 21

Preparations of Pt(II) complex of 2-amino-5-nitropyridine 33. Data from [49].

Scheme 22

Synthesis of novel photoactive Pt(IV) complexes with heterocyclic ligands [50].

Scheme 23

Nitropyridine complexes with antibacterial and antifungal activities. Data from [53].

Scheme 24

Synthesis of DNA-PK inhibitor AZD7648. Data from [54].

Scheme 25

Solid-phase synthesis of PDE4 inhibitors 69. Data from [55].

Scheme 26

Approach to potential inhibitor of cyclin G-associated kinase [56].

Scheme 27

Synthesis of semicarbazide-sensitive amine oxidase (SSAO) inhibitors 77. Data from [57].

Scheme 28

Synthesis of pyridine-based MALT1 inhibitors [59].

Scheme 29

Synthesis of 10-substituted 3,6-diazaphenothiazines 86 based on nitropyridines. Data from [60].

Scheme 30

Synthesis of Mannich bases 88 active against prostate cancer cells. Data from [61].

Scheme 31

Antitumor N-methylpyridinium salts. Data from [63].

Scheme 32

Synthesis of Shiff bases 92. Data from [64].

Scheme 33

Synthesis of antimicrobial pyridoxazinone derivatives. Data from [65].

Scheme 34

Synthesis of antimicrobial (pyridin-2-yl)piperazine derivatives 98. Data from [66].

Scheme 35

Synthesis of novel acyclic phosphonate nucleotide analogs 101–103. Data from [67].

Scheme 36

Synthesis of imidazo[4,5-b]pyridines 108 from 3,5-dinitropyridines. Data from [68].

Scheme 37

Synthetic route to PET tau tracer [¹¹C]PBB3. Data from [71].

Scheme 38

Radiochemical synthesis of [¹⁸F]4-amino-3-fluoro-5-methylpyridine. Data from [72].

Scheme 39

Radiosynthesis of P2X7R imaging agent ¹⁸F-JNJ64413739. Data from [74].

Scheme 40

Synthesis of [¹⁸F]fluoropyridine-losartan. Data from [75].

Scheme 41

The synthesis of [¹⁸F]FMN3PU via replacement of the nitro group [76].

Scheme 42

Synthesis of [¹⁸F]T807. Data from [77].