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Review
. 2021 Aug 8;14(8):779.
doi: 10.3390/ph14080779.

Synthesis and Biological Activities of Pyrazino[1,2- a]indole and Pyrazino[1,2- a]indol-1-one Derivatives

Kena Zhang  1 , Christine Tran  1 , Mouad Alami  1 , Abdallah Hamze  1 , Olivier Provot  1
Affiliations
Review

Synthesis and Biological Activities of Pyrazino[1,2- a]indole and Pyrazino[1,2- a]indol-1-one Derivatives

Kena Zhang et al. Pharmaceuticals (Basel). .

Abstract

This review concerns the synthesis and biological activities of pyrazino[1,2-a]indoles and pyrazino[1,2-a]indol-1-ones reported since 1997 and the discovery of biological activity of pyrazinoindole derivatives. In the first part, we first presented the synthetic routes that have been reported from a methodological point of view to access the pyrazinoindole unit according to cyclization reactions using or not using metal catalysts. Then, syntheses and neuropsychiatric, auto-immune, anti-infectious and anti-cancer properties of pyrazinoindoles were detailed. In the second part, we first reported the main accesses to pyrazinoindol-1-one substrates according to Michael reactions, metal-catalyzed and metal-free cyclization reactions. The syntheses and anti-cancer, anti-infectious, anti-allergenic and neuropsychiatric properties of pyrazinoindolones were next described and discussed.

Keywords: biological activity; catalysis; cyclization; pyrazinoindole; pyrazinoindolone.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Targets of this review and selection of biologically active tetrahydro-pyrazino[1,2-a]indoles 1a, 2a and dihydro-pyrazino[1,2-a]indol-1-ones 3a, 4a.
Scheme 1
Scheme 1
Synthesis of pyrazinoindoles.
Scheme 2
Scheme 2
Synthesis of 1,2,3,4-tetrahydro-pyrazinoindoles.
Scheme 3
Scheme 3
Synthesis of tetrahydro-pyrazinoindoles 36 and their binding data at the 5HT2C receptor subtype.
Figure 2
Figure 2
Tetrahydro-pyrazinoindoles 37 and their binding data at I2 and α-adrenergic receptors.
Scheme 4
Scheme 4
Synthesis of tetrahydro-pyrazinoindoles 1 and 39.
Scheme 5
Scheme 5
Synthesis of tetrahydro-pyrazinoindole 41 and human S1P1 cAMP EC50 values of derivatives 42a–d.
Scheme 6
Scheme 6
Synthesis of tetrahydro-pyrazinoindoles 2, 46a–c and effect in cAMP assay in hA1CHO cells.
Scheme 7
Scheme 7
Synthesis and anti-cancer properties of a selection of pyrazinoindoles 49a–c.
Scheme 8
Scheme 8
Synthesis of pyrazinoindoles 51 and their IC50 values against three human cancer cell lines.
Scheme 9
Scheme 9
Synthesis of pyrazinoindolones 54a,b.
Scheme 10
Scheme 10
Synthesis of pyrazinoindolones 61 and selected examples.
Scheme 11
Scheme 11
Synthesis of pyrazinoindolones 63 and selected examples.
Scheme 12
Scheme 12
Synthesis of pyrazinoindolones 65 and 66 and selected examples.
Scheme 13
Scheme 13
Synthesis of pyrazinoindolones 68 and selected examples.
Scheme 14
Scheme 14
Synthesis of pyrazinoindolones 70 and selected examples.
Scheme 15
Scheme 15
Synthesis of pyrazinoindolones 73 and selected examples.
Scheme 16
Scheme 16
Synthesis of optically active pyrazinoindolones 34a,b.
Scheme 17
Scheme 17
Synthesis of pyrazinoindolone 78a–d.
Scheme 18
Scheme 18
Synthesis of pyrazinoindolones 80 and selected examples.
Scheme 19
Scheme 19
Synthesis of pyrazinoindolones 83 as MAPK2 inhibitors.
Scheme 20
Scheme 20
Synthesis and evaluation of pyrazinoindolones 85 as anti-cancer agents.
Scheme 21
Scheme 21
Synthesis and evaluation of optically active 3-substituted pyrazinoindolones 88.
Scheme 22
Scheme 22
Synthesis and evaluation of optically active pyrazinoindolone 48.
Scheme 23
Scheme 23
Synthesis and cytotoxic properties of symmetrical and unsymmetrical diketopiperazines 95 and 95.
Scheme 24
Scheme 24
Secondary metabolites 96–98 from the marine fungus Neosartorya pseudofischeri.
Scheme 25
Scheme 25
Synthesis and evaluation of a selection of hydroxyimides 102 as antiviral compounds.
Scheme 26
Scheme 26
Synthesis of a dengue inhibitor 3.
Scheme 27
Scheme 27
Synthesis of 108a,b as 5-HT1A and 5-HT2 ligands.
Scheme 28
Scheme 28
Synthesis of pyrazinoindolones 4, 112, and affinity over histamine H3 receptor subtype.
Figure 3
Figure 3
Overview of tetrahydro-pyrazino[1,2-a]indoles having biological properties.
Figure 4
Figure 4
Overview of pyrazino[1,2-a]indol-1-ones having biological properties.
See this image and copyright information in PMC

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