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Review
. 2018 Oct 26;23(11):2783.
doi: 10.3390/molecules23112783.

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

Shu-Guang Zhang  1 , Chao-Gen Liang  2 , Wei-Hua Zhang  3
Affiliations
Review

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

Shu-Guang Zhang et al. Molecules. .

Abstract

Indazole-containing derivatives represent one of the most important heterocycles in drug molecules. Diversely substituted indazole derivatives bear a variety of functional groups and display versatile biological activities; hence, they have gained considerable attention in the field of medicinal chemistry. This review aims to summarize the recent advances in various methods for the synthesis of indazole derivatives. The current developments in the biological activities of indazole-based compounds are also presented.

Keywords: biological activities; indazole; synthesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Indazole nucleus.
Figure 2
Figure 2
Chemical structure of indazole-containing drugs 1–4.
Scheme 1
Scheme 1
Synthesis of 1H-indazoles 7 from tertiary amides 5.
Scheme 2
Scheme 2
Synthesis of 1H-indazoles 9 from hydrazones 8 via iodine-mediated aryl C-H amination.
Scheme 3
Scheme 3
Synthesis of 1H-indazoles 11 from hydrazones 10 via PIFA-mediated aryl C-H amination.
Scheme 4
Scheme 4
Synthesis of 1H-indazoles 13 from o-haloaryl N-tosylhydrazones 12 catalyzed by Cu2O.
Scheme 5
Scheme 5
Synthesis of 1H-indazoles 15 from o-haloaryl N-tosylhydrazones 14 catalyzed by Cu(OAc)2·H2O.
Scheme 6
Scheme 6
Synthesis of 1-aryl-5-nitro-1H-indazoles 17.
Scheme 7
Scheme 7
Pd-catalyzed benzannulation of 4-bromopyrazoles 18 for synthesis of 1H-indazoles 20.
Scheme 8
Scheme 8
Strategies for dialkenylation of pyrazoles 21 and synthesis of 1H-indazoles 24.
Scheme 9
Scheme 9
Synthesis of 1H-indazoles 26 from aldehyde hydrazones 25.
Scheme 10
Scheme 10
Synthesis of 1H-indazoles 29 from 2-aminobenzonitriles 27.
Scheme 11
Scheme 11
Synthesis of 1H-indazoles 32 from nitrosobenzenes 31.
Scheme 12
Scheme 12
Synthesis of 1H-indazoles 35 via Co(III)/Cu(II)-catalyzed C-H activation.
Scheme 13
Scheme 13
Synthesis of 1H-indazoles 38 from α-diazomethylphosphonates 36.
Scheme 14
Scheme 14
(a) Synthesis of 2H-indazoles 41 from benzamidines 40 via organophosphorus-mediated N-N bond formation (b) Synthesis of 2H-indazoles 44 from hydrazones 43 via organophosphorus-mediated N-N bond formation.
Scheme 15
Scheme 15
(a) Synthesis of 2H-indazoles 46 from o-nitrobenzaldimines 45 via 1,2,2,3,4,4-hexamethylphosphetane-mediated N-N bond formation (b) Synthesis of 2H-indazoles 46 from 2-nitrobenzaldehydes 47 and amines 48 by phospholene oxide with organosilanes-mediated N-N bond formation.
Scheme 16
Scheme 16
Synthesis of 3-perfluoroalkylated-2H-indazoles 54.
Scheme 17
Scheme 17
Co(III) or Re-catalyzed synthesis of N-aryl-2H-indazoles 57 from azobenzenes 55 and aldehydes 56.
Scheme 18
Scheme 18
(a) Rh-catalyzed synthesis of 2H-indazoles 60 from azobenzenes 58 and α-keto aldehydes 59 (b) Rh-catalyzed synthesis of 2H-indazoles 60 from azobenzenes 61 and sulfoxonium ylides 62.
Scheme 19
Scheme 19
Rh-catalyzed synthesis of 2H-indazoles 66 from azobenzenes 64 and acrylates 65.
Scheme 20
Scheme 20
(a) Rh-catalyzed synthesis of 2H-indazoles 69 from azoxybenzenes 67 and diazoesters 68 (b) Rh-catalyzed synthesis of 2H-indazoles 72 from azoxy 70 and alkynes 71.
Scheme 21
Scheme 21
Cu/Pd-catalyzed synthesis of 2H-indazoles 75 from 2-alkynyl-azobenzenes 73.
Scheme 22
Scheme 22
I2-mediated synthesis of 2H-indazoles 77 from ortho-alkylazobenzenes 76.
Scheme 23
Scheme 23
Copper-mediated synthesis of 2H-indazoles 80.
Figure 3
Figure 3
Chemical structures of (1R,2S)-2-(1H-Indazol-6-yl)spiro[cyclopropane-1,3’-indolin]-2’-one derivatives 81a–c.
Figure 4
Figure 4
Chemical structures of 5-(2,6-difluorophenyl)-3-(pyrazin-2-yl)-1H-indazoles derivatives 82 and 82a.
Figure 5
Figure 5
Chemical structure of 1H-pyrazolo[3,4-c]pyridine (6-azaindazole) derivative 83.
Figure 6
Figure 6
Chemical structure of azaindazole derivative 84.
Figure 7
Figure 7
Chemical structures of 1H-indazoles derivatives 85, 86 and 87.
Figure 8
Figure 8
Chemical structure of 1H-indazole derivative 88.
Figure 9
Figure 9
Chemical structures of 1H-indazol-3-amine derivatives 89 and 90.
Figure 10
Figure 10
Chemical structures of 3-(pyrrolopyridin-2-yl)indazole derivatives 91, 92 and 93.
Figure 11
Figure 11
Chemical structures of 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides derivatives 94, 95 and 96.
Figure 12
Figure 12
Chemical structure of N-(4-(1-(4-chlorineindazole))phenyl)-N-(4-chloro-3–trifluoro-methyl phenyl) urea 97.
Figure 13
Figure 13
Chemical structures of 1H-indazol-3-amine derivatives 98 and 99.
Figure 14
Figure 14
Chemical structure of 1H-indazol-3-amine derivative 100.
Figure 15
Figure 15
Chemical structures of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazole derivatives 101 and 102.
Figure 16
Figure 16
Chemical structures of pyridin-3-amine derivatives 103 and 104.
Figure 17
Figure 17
Chemical structure of 3-(5′-Substituted)–Benzimidazole-5-(1-(3,5-dichloropyridin-4-yl) ethoxy)-1H-indazole derivative 105.
Figure 18
Figure 18
Chemical structure of 1H-indazole derivative 106.
Figure 19
Figure 19
Chemical structure of 1H-indazole derivative 107.
Figure 20
Figure 20
Chemical structures of 1H-indazole derivatives 108 and 109.
Figure 21
Figure 21
Chemical structures of 3-carboxamido-2H-indazole-6-arylamide derivatives 110 and 111.
Figure 22
Figure 22
Chemical structure of 3-benzylindazoles derivative 112.
Figure 23
Figure 23
Chemical structure of imidazo-thiadiazole derivative 113.
Figure 24
Figure 24
Chemical structure of 1H-indazole derivative 114.
Figure 25
Figure 25
Chemical structures of 1H-indazole amide derivatives 115–118.
Figure 26
Figure 26
Chemical structure of 3(S)-thiomethyl pyrrolidine-1H-indazole derivative 119.
Figure 27
Figure 27
Chemical structure of 4-(((6-Bromo-1H-indazol-4-yl)amino)methyl)phenol 120.
Figure 28
Figure 28
Chemical structures of 3-substituted 1H-indazoles 121 and 122.
Figure 29
Figure 29
Chemical structures of 1H-indazole derivatives 123–125.
Figure 30
Figure 30
Chemical structures of 3-aminoindazole derivatives 126 and 127 as ALK inhibitors.
Figure 31
Figure 31
Chemical structure of indazole-based EGFR inhibitor 128.
Figure 32
Figure 32
Chemical structures of 1H-benzo[d]imidazol-2-yl)-1H-indazol derivatives 129 and 130.
Figure 33
Figure 33
Chemical structures of 2H-indazole derivatives 131 and 132.
Figure 34
Figure 34
Chemical structure of 1H-indazole-3-amine derivative 133.
Figure 35
Figure 35
Chemical structures of indazole–pyrimidine derivatives 134–137.
Figure 36
Figure 36
Chemical structures of 1H-indazole derivatives 138–141.
Figure 37
Figure 37
Chemical structures of indazole-3-carboxamide derivatives 142a–c.
Figure 38
Figure 38
Chemical structure of 1H-indazole derivative 143.
Figure 39
Figure 39
Chemical structures of 1H-indazole derivatives 144 and 145.
Figure 40
Figure 40
Chemical structures of 1H-indazole derivatives 146–148.
Figure 41
Figure 41
Chemical structures of 1H-indazole derivatives 149 and 150.
Figure 42
Figure 42
Chemical structures of 4-bromo-1H-indazole derivatives 151, 152 and 153.
Figure 43
Figure 43
Chemical structures of 2,3-diphenyl-2H-indazole derivatives 154–157.
Figure 44
Figure 44
Chemical structure of 1H-indazole derivative 158.
Figure 45
Figure 45
Chemical structure of 1,4-disubstituted-1H-indazole derivative 159.
Figure 46
Figure 46
Chemical structures of 1H-indazole derivatives 160 and 161.
Figure 47
Figure 47
Chemical structures of 1H-indazole ether derivatives 162 and 163a–c.
Figure 48
Figure 48
Chemical structure of 1H-indazole analogue 164.
Figure 49
Figure 49
Chemical structure of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine 165.
Figure 50
Figure 50
Chemical structures of 6 indazole ether-based derivatives 166 and 167.
Figure 51
Figure 51
Chemical structures of 1H-indazole derivatives 168 and 169.
Figure 52
Figure 52
Chemical structures of 4,6-disubstituted-1H-indazole derivatives 170 and 171.
Figure 53
Figure 53
Chemical structure of 4,6-disubstituted-1H-indazole derivative 172.
Figure 54
Figure 54
Chemical structure of N-alkylated-1H-indazole derivative 173.
Figure 55
Figure 55
Chemical structure of 1H-indazole derivative 174.
Figure 56
Figure 56
Chemical structure of 1H-indazole derivative 175 as LRRK2 inhibitor.
Figure 57
Figure 57
Chemical structures of N-alkylated indazole-5-carboxamide derivatives 176 and 177.
Figure 58
Figure 58
Chemical structures of 1H-indazole analogues 178 and 179.
Figure 59
Figure 59
Chemical structures of 4,6-disubstituted indazole analogues 180 and 181.
Figure 60
Figure 60
Chemical structure of 1H-indazole derivative 182.
Figure 61
Figure 61
Chemical structure of 3,4-dihydropyrazino[1,2-b]indazol-1(2H)-one derivative 183.
Figure 62
Figure 62
Chemical structures of 1H-indazole derivatives 184 and 185.
Figure 63
Figure 63
Chemical structures of 1-(2H-indazole-5-yl)pyridin-2(1H)-one derivatives 186 and 187.
Figure 64
Figure 64
Chemical structures of N-substituted prolinamido indazole derivatives 188, 189 and 190.
Figure 65
Figure 65
Chemical structures of 1H-indazole derivatives 191 and 192.
Figure 66
Figure 66
Chemical structure of 1H-indazole derivative 193.
Figure 67
Figure 67
Chemical structure of 1H-indazole derivative 194.
Figure 68
Figure 68
Chemical structures of 4-substituted-1H-indazole derivatives 195 and 196.
Figure 69
Figure 69
Chemical structure of 1H-indazole derivative 197.
Figure 70
Figure 70
Chemical structure of 1H-indazole derivative 198.
Figure 71
Figure 71
Chemical structure of 2H-indazole derivative 199.
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References

    1. Gao M.C., Xu B. Transition metal-involving synthesis and utilization of N-containing heterocycles: Exploration of nitrogen sources. Chem. Rec. 2016;16:1701–1714. doi: 10.1002/tcr.201600020. - DOI - PubMed
    1. Teixeira F.C., Ramos H., Antunes I.F., Curto M.J.M., Teresa Duarte M., Bento I. Synthesis and structural characterization of 1-and 2-substituted indazoles: Ester and carboxylic acid derivatives. Molecules. 2006;11:867–889. doi: 10.3390/11110867. - DOI - PMC - PubMed
    1. Vidyacharan S., Murugan A., Sharada D.S. C(sp2)-H Functionalization of 2H-indazoles at C3-position via palladium(II)-catalyzed isocyanide insertion strategy leading to diverse heterocycles. J. Org. Chem. 2016;81:2837–2848. doi: 10.1021/acs.joc.6b00048. - DOI - PubMed
    1. Shinde A.H., Vidyacharan S., Sharada D.S. BF3·OEt2 mediated metal-free one-pot sequential multiple annulation cascade (SMAC) synthesis of complex and diverse tetrahydroisoquinoline fused hybrid molecules. Org. Biomol. Chem. 2016;14:3207–3211. doi: 10.1039/C6OB00253F. - DOI - PubMed
    1. Behrouz S. Highly efficient one-pot three component synthesis of 2H-indazoles by consecutive condensation, C-N and N-N bond formations using Cu/Aminoclay/reduced grapheme oxide nanohybrid. J. Heterocyclic. Chem. 2017;54:1863–1871. doi: 10.1002/jhet.2777. - DOI

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