Skip to main content

Advertisement

SpringerLink
Log in

Pyrrolopyrazine derivatives: synthetic approaches and biological activities

  • Review Article
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Nitrogen-containing heterocycles were employed in different applications such as pharmaceuticals, organic materials, natural products, and mainly in bioactive molecules. Pyrrolopyrazine as a biologically active scaffold contains pyrrole and pyrazine rings. Compounds with this scaffold have widely exhibited different biological activities, such as antimicrobial, anti-inflammatory, antiviral, antifungal, antioxidant, antitumor, and kinase inhibitory. In addition, many pyrrolopyrazine derivatives have been isolated from plants, microbes, soil, marine life, and other sources. This review explained various synthetic routes for pyrrolopyrazine derivatives, including cyclization, ring annulation, cycloaddition, direct C-H arylation, and other methods. Besides, pyrrolopyrazines are classified into three chemical categories with two or three nitrogen atoms, indicating various biological activities. According to the findings, pyrrolo [1,2-a] pyrazine derivatives exhibited more antibacterial, antifungal, and antiviral activities, while 5H-pyrrolo [2,3-b] pyrazine derivatives showed more activity on kinase inhibition. However, studies show that the action mechanisms of pyrrolopyrazine derivatives are not clearly recognized. Moreover, despite the scaffold’s importance, there are only a few Structure-Activity Relationship (SAR) research on it. Therefore, the synthetic methods and biological activities of pyrrolopyrazine derivatives discussed in this paper will certainly help medicinal chemistry researchers design and synthesize new leads to treat various diseases.

Highlights

  • Pyrrolopyrazine scaffold is a nitrogen-containing heterocyclic compound that includes a pyrrole ring and a pyrazine ring.

  • A wide range of biological activities related to pyrrolopyrazine scaffold is discussed.

  • This review provides the recent efficient synthetic methods for the pyrrolopyrazines.

  • The pyrrolopyrazine structure is an attractive scaffold for drug discovery research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18
Fig. 19
Fig. 20
Fig. 21
Fig. 22
Fig. 23
Fig. 24
Fig. 25
Fig. 26
Fig. 27
Fig. 28
Fig. 29
Fig. 30
Fig. 31
Fig. 32
Fig. 33
Fig. 34

Similar content being viewed by others

Abbreviations

AIA:

Actinomycetes isolation agar media

MHA:

Mullar Hinton agar

IZ:

Inhibition zones

RSK:

p90 ribosomal S6 kinase

EIC:

Effective inhibitory concentration

ROS:

Reactive oxygen species

CAT:

Catalase

GPER:

G-protein coupled estrogen receptor

IRAK4:

Interleukin-1 receptor associated kinase 4

FGFR inhibitors:

Fibroblast growth factor receptor

RSV:

Respiratory syncytial virus

PARP:

Poly ADP-ribose polymerase

IC50 :

Inhibitory concentration

SAR:

Structure activity relationship

CLSM:

Confocal laser scanning microscopy

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

Eis:

Enhanced intracellular survival

MIC:

Minimum inhibitory concentration

MBC:

Minimum bactericidal concentration

MDA:

Malondialdehyde

HIF-1:

Hypoxia-inducible factor-1

AML:

Acute myeloid leukemia

NNRTI:

Non-nucleoside reverse transcriptase inhibitors

LAB:

Lactic acid bacteria

References

  1. Vitaku E, Smith DT, Njardarson JT. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among us FDA approved pharmaceuticals: miniperspective. J Med Chem. 2014;57:10257–74. https://doi.org/10.1021/jm501100b.

    Article  CAS  PubMed  Google Scholar 

  2. Pozharskii A, Soldatenkov A, Katritzky A Heterocycles in life and society: an introduction to heterocyclic chemistry, biochemistry and applications, Wiely; 2nd ed. John Wiley & Sons, Chichester, U.K. 2011.

  3. Miniyar PB, Murumkar PR, Patil PS, Barmade MA, Bothara KG. Unequivocal role of pyrazine ring in medicinally important compounds: a review. Mini Rev Med Chem. 2013;13:1607–25.

    Article  CAS  Google Scholar 

  4. Terenin V, Kabanova E, Feoktistova E. Synthesis and properties of pyrrolo [1, 2-a] pyrazines. Chem Heterocycl Compd. 1991;27:1037–48. https://doi.org/10.1007/BF00486793.

    Article  Google Scholar 

  5. Sanner MA. Selective dopamine D4 receptor antagonists. Expert Opin Ther Pat. 1998;8:383–93. https://doi.org/10.1517/13543776.8.4.383.

    Article  CAS  Google Scholar 

  6. Prochaska HJ, Fernandes CL, Pantoja RM, Chavan SJ. Inhibition of human immunodeficiency virus type 1 long terminal repeat-driven transcription by anin vivometabolite of oltipraz: implications for antiretroviral therapy. Biochem Biophys Res Commun. 1996;221:548–53. https://doi.org/10.1006/bbrc.1996.0633.

    Article  CAS  PubMed  Google Scholar 

  7. Baskaran R, Mohan P, Madanan M, Kumar A, Palaniswami M. Characterization and antimicrobial activity of Streptomyces sp. DOSMB-A107 isolated from mangrove sediments of Andaman Island, India. 2015; 44: 714–23. http://hdl.handle.net/12345 6789/34797.

  8. Lim J, Altman MD, Baker J, Brubaker JD, Chen H, Chen Y, et al. Identification of N-(1H-pyrazol-4-yl) carboxamide inhibitors of interleukin-1 receptor associated kinase 4: bicyclic core modifications. Bioorg Med Chem Lett. 2015;25:5384–8. https://doi.org/10.1016/j.bmcl.2015.09.028.

    Article  CAS  PubMed  Google Scholar 

  9. Awla HK, Kadir J, Othman R, Rashid TS, Wong M-Y. Bioactive compounds produced by Streptomyces sp. isolate UPMRS4 and antifungal activity against Pyricularia oryzae. Am J Plant Sci. 2016;7:1077–85. https://doi.org/10.4236/ajps.2016.77103

    Article  CAS  Google Scholar 

  10. Mokrov G, Deeva O, Gudasheva T, Yarkov S, Yarkova M, Seredenin S. Design, synthesis and anxiolytic-like activity of 1-arylpyrrolo [1, 2-a] pyrazine-3-carboxamides. Bioorg Med Chem. 2015;23:3368–78. https://doi.org/10.1016/j.bmc.2015.04.049.

    Article  CAS  PubMed  Google Scholar 

  11. Maggiolini M, Santolla MF, Avino S, Aiello F, Rosano C, Garofalo A, et al. Identification of two benzopyrroloxazines acting as selective GPER antagonists in breast cancer cells and cancer-associated fibroblasts. Future Med Ltd. 2015;7:437–48. https://doi.org/10.4155/fmc.15.3.

    Article  CAS  Google Scholar 

  12. Ibrahim MA, Abou-Seri SM, Hanna MM, Abdalla MM, El Sayed NA. Design, synthesis and biological evaluation of novel condensed pyrrolo [1, 2-c] pyrimidines featuring morpholine moiety as PI3Kα inhibitors. Eur J Med Chem. 2015;99:1–13. https://doi.org/10.1016/j.ejmech.2015.05.036.

    Article  CAS  PubMed  Google Scholar 

  13. Basceken S, Balci M. Design of pyrazolo-pyrrolo-pyrazines and pyrazolo-pyrrolo-diazepines via AuCl3-catalyzed and NaH-supported cyclization of N-propargyl pyrazoles. J Org Chem. 2015;80:3806–14. https://doi.org/10.1021/acs.joc.5b00034.

    Article  CAS  PubMed  Google Scholar 

  14. Medvedeva SM, Shikhaliev KS. The synthesis of novel annelated 2-oxopiperazines by the interaction methyl (3-oxopiperazin-2-ylidene) acetate with an N-arylmaleimides. Mater Sci Eng A. 2015;5:310–3. https://doi.org/10.17265/2161-6213/2015.7-8.007.

    Article  CAS  Google Scholar 

  15. Martinez-Ariza G, Mehari BT, Pinho LA, Foley C, Day K, Jewett JC, et al. Synthesis of fluorescent heterocycles via a Knoevenagel/[4+ 1]-cycloaddition cascade using acetyl cyanide. Org Biomol Chem. 2017;15:6076–9. https://doi.org/10.1039/C7OB01239J.

    Article  CAS  PubMed  Google Scholar 

  16. Park S, Jung Y, Kim I. Diversity-oriented decoration of pyrrolo [1, 2-a] pyrazines. Tetrahedron. 2014;70:7534–50. https://doi.org/10.1016/j.tet.2014.08.003.

    Article  CAS  Google Scholar 

  17. Simpson I, St-Gallay SA, Stokes S, Whittaker DT, Wiewiora R. An efficient one-pot synthesis of 2-bromo-6-aryl [5H] pyrrolo [2, 3-b] pyrazines. Tetrahedron Lett. 2015;56:1492–5. https://doi.org/10.1016/j.tetlet.2015.02.005.

    Article  CAS  Google Scholar 

  18. Moradi L, Piltan M, Rostami H, Abasi G. One-pot synthesis of pyrrolo [1, 2-a] pyrazines via three component reaction of ethylenediamine, acetylenic esters and nitrostyrene derivatives. Chin Chem Lett. 2013;24:740–2. https://doi.org/10.1016/j.cclet.2013.04.038.

    Article  CAS  Google Scholar 

  19. Voievudskyi M, Astakhina V, Kryshchyk O, Petuhova O, Shyshkina S. Synthesis and reactivity of novel pyrrolo [1, 2-a] pyrazine derivatives. Monatsh Chem. 2016;147:783–9. https://doi.org/10.1007/s00706-015-1619-0.

    Article  CAS  Google Scholar 

  20. Sobenina LN, Sagitova EF, Ushakov IA, Trofimov BA. Transition-metal-free synthesis of pyrrolo [1, 2-a] pyrazines via intramolecular cyclization of N-propargyl (pyrrolyl) enaminones. Synthesis. 2017;49:4065–81. https://doi.org/10.1055/s-0036-1588454.

    Article  CAS  Google Scholar 

  21. Tiwari R, Nath M. Novel π-extended pyrrolo [1, 2-a] pyrazinoporphyrins: synthesis, photophysical properties and mercuric ion recognition. Dyes Pigm. 2018;152:161–70. https://doi.org/10.1016/j.dyepig.2018.01.041.

    Article  CAS  Google Scholar 

  22. Singh DK, Nath M. Ambient temperature synthesis of β, β′-fused nickel (ii) pyrrolo [1, 2-a] pyrazinoporphyrins via a DBSA-catalyzed Pictet–Spengler approach. Org Biomol Chem. 2015;13:1836–45. https://doi.org/10.1039/C4OB02370F.

    Article  CAS  PubMed  Google Scholar 

  23. Karmakar A, Ramalingam S, Basha M, Indasi GK, Belema M, Meanwell NA, et al. Facile access to 1, 4-disubstituted pyrrolo [1, 2-a] pyrazines from α-aminoacetonitriles. Synthesis. 2020;52:441–9. https://doi.org/10.1055/s-0039-1690699.

    Article  CAS  Google Scholar 

  24. Aslanoglu F, Basceken S, Balci M. Synthesis of pyrrolo-pyrrolo-pyrazines via the Pd/C-catalyzed cyclization of N-propargyl pyrrolinyl-pyrrole derivatives. Tetrahedron Lett. 2019;60:449–51. https://doi.org/10.1016/j.tetlet.2019.01.004.

    Article  CAS  Google Scholar 

  25. Menges N, Sari O, Abdullayev Y, Erdem SS, Balci M. Design and synthesis of pyrrolotriazepine derivatives: an experimental and computational study. J Org Chem. 2013;78:5184–95. https://doi.org/10.1021/jo4001228.

    Article  CAS  PubMed  Google Scholar 

  26. Keskin S, Balci M. Intramolecular heterocyclization of O-propargylated aromatic hydroxyaldehydes as an expedient route to substituted chromenopyridines under metal-free conditions. Org Lett. 2015;17:964–7. https://doi.org/10.1021/acs.orglett.5b00067.

    Article  CAS  PubMed  Google Scholar 

  27. Taskaya S, Menges N, Balci M. Gold-catalyzed formation of pyrrolo-and indolo-oxazin-1-one derivatives: The key structure of some marine natural products. Beilstein J Org Chem. 2015;11:897–905. https://doi.org/10.3762/bjoc.11.101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Guven S, Ozer MS, Kaya S, Menges N, Balci M. Gold-catalyzed oxime–oxime rearrangement. Org Lett. 2015;17:2660–3. https://doi.org/10.1021/acs.orglett.5b01041.

    Article  CAS  PubMed  Google Scholar 

  29. Ozer MS, Menges N, Keskin S, Sahin E, Balci M. Synthesis of pyrrole-fused C, N-cyclic azomethine imines and pyrazolopyrrolopyrazines: analysis of their aromaticity using nucleus-independent chemical shifts values. Org Lett. 2016;18:408–11. https://doi.org/10.1021/acs.orglett.5b03434.

    Article  CAS  PubMed  Google Scholar 

  30. Hoplamaz E, Keskin S, Balci M. Regioselective synthesis of benzo [h][1, 6]‐naphthyridines and chromenopyrazinones through alkyne cyclization. Eur J Org Chem. 2017;2017:1489–97. https://doi.org/10.1002/ejoc.201601661.

    Article  CAS  Google Scholar 

  31. Yenice I, Basceken S, Balci M. Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties. Beilstein J Org. Chem 2017;13:825–34. https://doi.org/10.3762/bjoc.13.83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Baskın D, Çetinkaya Y, Balci M. Synthesis of dipyrrolo-diazepine derivatives via intramolecular alkyne cyclization. Tetrahedron. 2018;74:4062–70. https://doi.org/10.1016/j.tet.2018.06.013.

    Article  Google Scholar 

  33. Berlin A, Martina S, Pagani G, Schiavon G, Zotti G. Synthesis of the parent systems of dipyrrolo [1, 2-a: 2'1’-c] pyrazine and of dipyrrolo [1, 2-a: 2’, 1’-c] quinoxaline. Heterocycles (Sendai).1991;32:85–92.

    Article  CAS  Google Scholar 

  34. Kim JT, Gevorgyan V. Selective partial reduction of various heteroaromatic compounds with bridgehead nitrogen via Birch reduction protocol. J Org Chem. 2005;70:2054–9. https://doi.org/10.1021/jo0479157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mínguez JM, Castellote MI, Vaquero JJ, García-Navio JL, Alvarez-Builla J, Castano O, et al. Pyrrolodiazines. 2. structure and chemistry of pyrrolo [1, 2-a] pyrazine and 1, 3-dipolar cycloaddition of its azomethine ylides. J Org Chem. 1996;61:4655–65. https://doi.org/10.1021/jo9600969.

    Article  PubMed  Google Scholar 

  36. Terenin V, Sumtsova E, Kovalkina M, Vatsadze S, Kabanova E, Pleshkova A, et al. Dipyrrolo [1, 2-a; 2’:, 1’-c] pyrazines. 7. electrophilic substitution of dipyrrolo [1, 2-a; 2’, 1’-c] pyrazines and 5, 6-dihydrodipyrrolo [1, 2-a; 2’, 1’-c] pyrazines via formylation of dipyrrolo [1, 2-a; 2’:, 1’-c] pyrazines. Chem Heterocycl Compd. 2003;39:1487–91. https://doi.org/10.1023/B:COHC.0000014413.07428.a1.

    Article  CAS  Google Scholar 

  37. Sari O, Seybek AF, Kaya S, Menges N, Erdem SS, Balci M. Mechanistic insights into the reaction of N‐propargylated pyrrole‐and indole‐carbaldehyde with ammonia, alkyl amines, and branched amines: A synthetic and theoretical investigation. Eur J Org Chem. 2019;2019:5261–74. https://doi.org/10.1002/ejoc.201900084.

    Article  CAS  Google Scholar 

  38. Bae GH, Kim S, Lee NK, Dagar A, Lee JH, Lee J, et al. Facile approach to benzo [d] imidazole-pyrrolo [1, 2-a] pyrazine hybrid structures through double cyclodehydration and aromatization and their unique optical properties with blue emission. RSC Adv. 2020;10:7265–88. https://doi.org/10.1039/D0RA01140A.

    Article  CAS  Google Scholar 

  39. Beccalli EM, Broggini G, Martinelli M, Paladino G. Pd-catalyzed intramolecular cyclization of pyrrolo-2-carboxamides: regiodivergent routes to pyrrolo-pyrazines and pyrrolo-pyridines. Tetrahedron. 2005;61:1077–82. https://doi.org/10.1016/j.tet.2004.11.066.

    Article  CAS  Google Scholar 

  40. Hordiyenko OV, Rudenko IV, Zamkova IA, Denisenko OV, Biitseva AV, Arrault A, et al. Facile synthesis of hydrazine derivatives of 5H-pyrrolo [3, 4-b] pyrazine and 1H-pyrrolo [3, 4-b] quinoxaline. Synthesis. 2013;45:3375–82. https://doi.org/10.1055/s-0033-1340042.

    Article  CAS  Google Scholar 

  41. Chen W, Hu M, Wu J, Zou H, Yu Y. Domino approach for the synthesis of pyrrolo [1, 2-α] pyrazine from vinyl azides. Org Lett. 2010;12:3863–5. https://doi.org/10.1021/ol101538x.

    Article  CAS  PubMed  Google Scholar 

  42. El‐Sayed HA, Said SA. Direct synthesis of multi‐functional pyrimidine, pyrazine, and pyridine scaffolds via inter‐and intramolecular annulations of 3‐amino‐thieno [2, 3‐b] pyridine‐2‐carboxylate. J Heterocycl Chem. 2019;56:1030–7. https://doi.org/10.1002/jhet.3488.

    Article  Google Scholar 

  43. Vessally E, Hosseinian A, Edjlali L, Bekhradnia A, Esrafili D, New M. page to access pyrazines and their ring fused analogues: Synthesis from N-propargylamines. Curr Org Synth. 2017;14:557–67.

    Article  CAS  Google Scholar 

  44. Verbitskiy E, Slepukhin P, Ezhikova M, Kodess M, Rusinov G, Charushin V. Reactions of σ H-adducts of 1-ethyl-1, 4-diazinium salts with arylalkynes as a one-step approach to pyrrolo [1, 2-a] pyrazine derivatives. Russ Chem Bull. 2009;58:1291–3. https://doi.org/10.1007/s11172-009-0169-1.

    Article  CAS  Google Scholar 

  45. Zubkov FI, Orlova DN, Zaytsev VP, Voronov AA, Nikitina EV, Khrustalev VN, et al. Short approach to pyrrolopyrazino-, pyrrolodiazepino-isoindol,es and their benzo analogues via the IMDAF reaction. Curr Org Synth. 2017;14:733–46. https://doi.org/10.2174/1570179414666161116123221.

    Article  CAS  Google Scholar 

  46. Chu X, Zhang Z, Wang C, Chen X, Wang B, Ma C. CH3CO2H-prompted three components tandem reaction: An efficient and practical approach to trisubstituted pyrrolo [1, 2-a] pyrazines. Tetrahedron. 2017;73:7185–9. https://doi.org/10.1016/j.tet.2017.10.06.

    Article  CAS  Google Scholar 

  47. Krupa A, Descamps M, Willart J, Strach B, Wyska E, Jachowicz R, et al. High-energy ball milling as green process to vitrify tadalafil and improve bioavailability. Mol Pharm. 2016;13:3891–902. https://doi.org/10.1021/acs.molpharmaceut.6b00688.

    Article  CAS  PubMed  Google Scholar 

  48. Turkett JA, Ringuette AE, Lindsley CW, Bender AM. Synthesis of substituted 6, 7-dihydro-5 H-pyrrolo [2, 3-c] pyridazines/pyrazines via catalyst-free tandem hydroamination–aromatic substitution. J Org Chem. 2020;85:6123–30. https://doi.org/10.1021/acs.joc.9b03463.

    Article  CAS  PubMed  Google Scholar 

  49. Singh DK, Kim I. Electrophilic acetylation and formylation of pyrrolo [1, 2-a] pyrazines: substituent effects on regioselectivity. Org Chem. 2019, 8–21. https://doi.org/10.24820/ark.5550190.p010.807.

  50. Kim J, Park M, Choi J, Singh DK, Kwon HJ, Kim SH, et al. Design, synthesis, and biological evaluation of novel pyrrolo [1, 2-a] pyrazine derivatives. Bioorg Med Chem Lett. 2019;29:1350–6. https://doi.org/10.1016/j.bmcl.2019.03.044.

    Article  CAS  PubMed  Google Scholar 

  51. Terenin V, Kabanova E, Tselishcheva N, Ivanov A, Zyk N. Trifluoroacetylation of pyrrolo [1, 2-a] pyrazines. Chem Heterocycl Compd. 2007;43:1038–43. https://doi.org/10.1007/s10593-007-0162-2.

    Article  CAS  Google Scholar 

  52. Terenin V, Butkevich M, Ivanov A, Kabanova E. Acylation of pyrrolo [1, 2-a] pyrazines. Chem Heterocycl Compd. 2008;44:200–7. https://doi.org/10.1007/s10593-008-0026-4.

    Article  CAS  Google Scholar 

  53. Terenin V, Butkevich M, Ivanov A, Tselischeva N, Kabanova E. Formylation of pyrrolo-[1, 2-a] pyrazines. Chem Heterocycl Compd. 2008;44:73–77. https://doi.org/10.1007/s10593-008-0010-z.

    Article  CAS  Google Scholar 

  54. Hu SB, Chen ZP, Song B, Wang J, Zhou YG. Enantioselective hydrogenation of pyrrolo [1, 2‐a] pyrazines, heteroaromatics containing two nitrogen atoms. Adv Synth Catal. 2017;359:2762–7. https://doi.org/10.1002/adsc.201700431.

    Article  CAS  Google Scholar 

  55. El Kazzouli S, Koubachi J, El Brahmi N, Guillaumet G. Advances in direct C–H arylation of 5, 5-6, 5-and 6, 6-fused-heterocycles containing heteroatoms (N, O, S). RSC Adv. 2015;5:15292–327. https://doi.org/10.1039/C4RA15384G.

    Article  CAS  Google Scholar 

  56. Aziz J, Piguel S. An update on direct C–H bond functionalization of nitrogen-containing fused heterocycles. Synthesis. 2017;49:4562–85. https://doi.org/10.1055/s-0036-1590859.

    Article  CAS  Google Scholar 

  57. Chervyakov A, Slepukhin P, Dmitriev M, Maslivets A. Synthesis of 8-aroylpyrrolo [1, 2-a] pyrazine-1, 6, 7 (2H)-triones and their reaction with water. New analogs of cyclic dipeptides. Russ. J Org Chem. 2015;51:1587–92. https://doi.org/10.1134/S1070428015110123.

    Article  CAS  Google Scholar 

  58. Biitseva AV, Rudenko IV, Hordiyenko OV, Omelchenko IV, Arrault A. Synthesis of 5H-pyrrolo [3, 4-b] pyrazine-based peptidomimetics. Synthesis. 2015;47:3733–40. https://doi.org/10.1055/s-0035-1560184.

    Article  CAS  Google Scholar 

  59. Tat’yana AS, Vasilin VK, Krapivin GD. Furan ring transformation as key stage in the synthesis of 5H, 12H-benzo [4, 5] imidazo [1, 2-a] pyrrolo [1, 2-d] pyrazines. Chem Heterocycl Compd. 2018;54:188–96. https://doi.org/10.1007/s10593-018-2253-7.

    Article  Google Scholar 

  60. Rostami H, Shiri L. One‐pot multicomponent synthesis of pyrrolo [1, 2‐a] pyrazines in water catalyzed by Fe3O4@ SiO2‐OSO3H. ChemistrySelect. 2018;3:13487–92. https://doi.org/10.1002/slct.201802759.

    Article  CAS  Google Scholar 

  61. Chithanna S, Yang D-Y. Multicomponent synthesis of 1, 3-diketone-linked N-substituted pyrroles, pyrrolo [1, 2-a] pyrazines, pyrrolo [1, 4] diazepines, and pyrrolo [1, 4] diazocines. J Org Chem. 2019;84:1339–47. https://doi.org/10.1021/acs.joc.8b02819.

    Article  CAS  PubMed  Google Scholar 

  62. Yaremchuk IO, Muzychka LV, Smolii OB, Kucher OV, Shishkina SV. Synthesis of novel 1, 2-dihydropyrrolo [1, 2-a] pyrazin-1 (2H)-one derivatives. Tetrahedron Lett. 2018;59:442–4. https://doi.org/10.1016/j.tetlet.2017.12.065.

    Article  CAS  Google Scholar 

  63. Cervera‐Villanueva JMJ, Viveros‐Ceballos JL, Ordóñez M. First practical synthesis of novel 1‐phosphonylated pyrrolo [1, 2‐a] pyrazine derivatives. Heteroat Chem. 2017;28:e21398 https://doi.org/10.1002/hc.21398.

    Article  Google Scholar 

  64. Ghandi M, Salahi S, Taheri A, Abbasi A. One-pot synthesis of novel 1-(1H-tetrazol-5-yl)-1, 2, 3, 4-tetrahydropyrrolo [1, 2-a] pyrazine derivatives via an Ugi-azide 4CR process. Mol Divers. 2018;22:291–303. https://doi.org/10.1007/s11030-017-9801-4.

    Article  CAS  PubMed  Google Scholar 

  65. Letten AD, Ke PJ, Fukami T. Linking modern coexistence theory and contemporary niche theory. Ecol Monogr. 2017;87:161–77. https://doi.org/10.1002/ecm.1242.

    Article  Google Scholar 

  66. Meti P, Gong Y-D. Pyrrolopyrazine-based triads decorated with donor-acceptor groups: pH and polarity induced visible color switching sensors. Dyes Pigm 2020;181:108532 https://doi.org/10.1016/j.dyepig.2020.108532.

    Article  CAS  Google Scholar 

  67. Khan ST, Yu P, Chantrapromma S, Afza N, Nelofar A. N-[2-(3-Methyl-1-oxo-1, 2-dihydropyrrolo [1, 2-a] pyrazin-2-yl) ethyl] methanesulfonamide. Acta Crystallographica Section E: Structure Reports Online. 2010;66:o1957. https://doi.org/10.1107/S1600536810026115.

  68. Huang W-X, Yu C-B, Shi L, Zhou Y-G. Iridium-catalyzed asymmetric hydrogenation of pyrrolo [1, 2-a] pyrazinium salts. Org Lett. 2014;16:3324–7. https://doi.org/10.1021/ol5013313.

    Article  CAS  PubMed  Google Scholar 

  69. Meti P, Lee E-S, Yang J-W, Gong Y-D. Regioselective synthesis of dipyrrolopyrazine (DPP) derivatives via metal free and metal catalyzed amination and investigation of their optical and thermal properties. RSC Adv. 2017;7:18120–31. https://doi.org/10.1039/C7RA01795B.

    Article  CAS  Google Scholar 

  70. Zhang Y, Lei X-X. Crystal structure of hexahydro-7-hydroxy-3-(2-methylpropyl) pyrrolo [1, 2-a] pyrazine-1, 4-dione, C11H18N2O3. Z Kristallogr NCS. 2015;230:199–200. https://doi.org/10.1515/ncrs-2014-9061.

    Article  CAS  Google Scholar 

  71. Wang D-W, Wang F. Crystal structure of diaqua-dinitrato-κ1O-bis (2-(pyridin-4-ylthio)-pyrazine-κ1N) cadmium (II), C18H18CdN8O8S2. Z Kristallogr NCS. 2015;230:263–4. https://doi.org/10.1515/ncrs-2014-0265.

    Article  CAS  Google Scholar 

  72. Manimaran M, Gopal JV, Kannabiran K. Antibacterial activity of Streptomyces sp. VITMK1 isolated from mangrove soil of Pichavaram, Tamil Nadu, India. Proc Natl Acad Sci India Sect B Biol Sci. 2017;87:499–506. https://doi.org/10.1007/s40011-0150619-5.

    Article  CAS  Google Scholar 

  73. Klusaite A, Vickackaite V, Vaitkeviciene B, Karnickaite R, Bukelskis D, Kieraite-Aleksandrova I, et al. Characterization of antimicrobial activity of culturable bacteria isolated from Krubera-Voronja Cave. Int J Speleol. 2016;45:275–87. https://doi.org/10.5038/1827-806X.45.3.1978.

    Article  Google Scholar 

  74. Naik C, Shivasharanappa Chandrappa Gadal RT, Bhat AR, Sharanya B. Chandini L. Isolation, identification, and evaluation of antioxidant, anti-inflammatory and antimitotic properties of bio-active pigment from Rhodococcus corynebacterioides SCG11. Int J Appl Microbiol Biotechnol Res. 2020;8:1–14. https://doi.org/10.33500/ijambr.2020.08.001.

    Article  Google Scholar 

  75. Mohan G, Thangappanpillai AKT, Ramasamy B. Antimicrobial activities of secondary metabolites and phylogenetic study of sponge endosymbiotic bacteria, Bacillus sp. at Agatti Island, Lakshadweep Archipelago. Biotechnol Rep. 2016;11:44–52. https://doi.org/10.1016/j.btre.2016.06.001.

    Article  Google Scholar 

  76. Kiran GS, Priyadharsini S, Sajayan A, Ravindran A, Selvin J. An antibiotic agent pyrrolo [1, 2-a] pyrazine-1, 4-dione, hexahydro isolated from a marine bacteria Bacillus tequilensis MSI45 effectively controls multi-drug resistant Staphylococcus aureus. RSC Adv. 2018;8:17837–46. https://doi.org/10.1039/C8RA00820E.

    Article  CAS  Google Scholar 

  77. Nahar N, Rahman MS, Rahman SM, Moniruzzaman M. GC-MS analysis and antibacterial activity of trigonella foenum-graecum against bacterial pathogens. Free Rad Antiox. 2016;6:109–14. https://doi.org/10.5530/fra.2016.1.13.

    Article  CAS  Google Scholar 

  78. Zhenting L. Screening of antibacterial active marine actinomycetes and separation and structure analysis of active natural substances. Fujian Medical University, 2017.

  79. Kumari N, Menghani E, Mithal R. GCMS analysis of compounds extracted from actinomycetes AIA6 isolates and study of its antimicrobial efficacy. Indian J Chem Techn. 2019;26:362–70. http://nopr.niscair.res.in/handle/123456789/49682.

  80. Murniasih T, Maryani M, Untari F. Identification of the Bacterium FJAT secondary metabolite by gas chromatography-mass spectrometer and their antimicrobial activity test. Adv Sci Lett. 2017;23:6516–20. https://doi.org/10.1166/asl.2017.9670.

    Article  Google Scholar 

  81. Kavitha A, Savithri HS. Biological significance of marine actinobacteria of east coast of Andhra Pradesh, India. Front Microbiol. 2017;8:1201 https://doi.org/10.3389/fmicb.2017.01201.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Garzan A, Willby MJ, Ngo HX, Gajadeera CS, Green KD, Holbrook SY, et al. Combating enhanced intracellular survival (Eis)-mediated kanamycin resistance of Mycobacterium tuberculosis by novel pyrrolo [1, 5-a] pyrazine-based Eis inhibitors. ACS Infect Dis. 2017;3:302–9. https://doi.org/10.1021/acsinfecdis.6b00193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kolli MK, Padi KR, Singh N, Tatipamula VB, Reddy R. Synthesis and in vitro antimycobacterialactivity of some novel pyrrolo [1, 2-A] pyrazine incorporated indolizine derivatives. Der Pharma Chem. 2018;10:153–8.

    CAS  Google Scholar 

  84. Akter MN, Hashim R, Sutriana A, Nor SAM. Effectiveness of the fermentative extract of Lactobacillus acidophilus as antimicrobials against Aeromonas hydrophila. J Kedokt Hewan. 2018;12:81–88. https://doi.org/10.21157/j.ked.hewan.v12i4.11920.

    Article  Google Scholar 

  85. Rajivgandhi G, Vijayan R, Maruthupandy M, Vaseeharan B, Manoharan N. Antibiofilm effect of Nocardiopsis sp. GRG 1 (KT235640) compound against biofilm forming gram negative bacteria on UTIs. Microb Pathog. 2018;118:190–8. https://doi.org/10.1016/j.micpath.2018.03.011.

    Article  CAS  PubMed  Google Scholar 

  86. Mahmud M, Podder S. Retracted: Bioactive compounds identified from cellulytic bacteria isolated from food dissipated and their screening for potential antimicrobial and cytotoxicity activities. Asian J Biotechnol Bioresour. 2018;4:1–9. https://doi.org/10.9734/AJB2T/2018/43320.

    Article  Google Scholar 

  87. Moradi M, Mardani K, Tajik H. Characterization and application of postbiotics of Lactobacillus spp. on Listeria monocytogenes in vitro and in food models. Lebensm Wiss Technol. 2019;111:457–64. https://doi.org/10.1016/j.lwt.2019.05.072.

    Article  CAS  Google Scholar 

  88. Dermawan AM, Julianti E, Putra MY. Identification and evaluation of antibacterial compounds from the Vibrio sp. associated with the ascidian pycnoclavella diminuta. Int J Pharm Sci Res. 2019;6:142–8. https://doi.org/10.7454/psr.v6i3.4673.

    Article  Google Scholar 

  89. Singh VK, Mishra A, Jha B. 3-Benzyl-hexahydro-pyrrolo [1, 2-a] pyrazine-1, 4-dione extracted from Exiguobacterium indicum showed anti-biofilm activity against Pseudomonas aeruginosa by attenuating quorum sensing. Front Microbiol. 2019;10:1269 https://doi.org/10.3389/fmicb.2019.01269.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Thacharodi A, Reghu AP, Priyadharshini R, Karthikeyan G, Thacharodi D. Bioprospecting of halotolerant bacillus subtilis: A study depicting its potential antimicrobial activity against clinically important pathogens. Indian J Sci Technol. 2019;12:1–7. https://doi.org/10.17485/ijst/2019/v12i22/144660.

    Article  Google Scholar 

  91. Sheoran N, Nadakkakath AV, Munjal V, Kundu A, Subaharan K, Venugopal V, et al. Genetic analysis of plant endophytic Pseudomonas putida BP25 and chemo-profiling of its antimicrobial volatile organic compounds. Microbiol Res. 2015;173:66–78. https://doi.org/10.1016/j.micres.2015.02.001.

    Article  CAS  PubMed  Google Scholar 

  92. Kumari N, Menghani E, Mithal R. GCMS analysis & assessment of antimicrobial potential of rhizospheric Actinomycetes of AIA3 isolate. Indian J Tradit Know (IJTK). 2019; 19: 111–9. http://nopr.niscair.res.in/handle/123456789/52826.

  93. Hermann JC, Kennedy-Smith J, Lucas MC, Padilla F, Schoenfeld RC, Wovkulich PM. Pyrrolo [2, 3-B] pyrazines as SYK inhibitors, in, Google Patents, 2016.

  94. Goldstein DM, Brameld KA, Owens T. Substituted pyrrolo [2, 3-b] pyrazines as JAK3 inhibitors, in, Google Patents, 2017.

  95. Jayanthan A, Nagireddy JR, Annedi S, van Drie JH, Daynard TS, Huynh M-M. Substituted tetrahydropyrido [3′, 2′: 4, 5] pyrrolo [1, 2-a] pyrazine-2-carboxamides as RSK inhibitors, in, Google Patents, 2017.

  96. Jayanthan A, Nagireddy JR, Annedi S, van Drie JH, Daynard TS, Huynh M.-m. Substituted tetrahydropyrido [3′, 2′: 4, 5] pyrrolo [1, 2-α] pyrazine-2-carboxamides as RSK inhibitors, in, Google Patents, 2018.

  97. Othman AA, Mohamed M-EF, Klünder B, Pangan AL. Processes for the preparation of (3S, 4R)-3-ethyl-4-(3H-imidazo [1, 2-a] pyrrolo [2, 3-e]-pyrazin-8-yl)-n-(2, 2, 2-trifluoroethyl) pyrrolidine-1-carb oxamide and solid state forms thereof, in, Google Patents, 2020.

  98. Jalaluldeen AM, Sijam K, Othman R, Ahmad ZAM. Growth characteristics and production of secondary metabolites from selected Streptomyces species isolated from the Rhizosphere of Chili Plant. Int J Enhanc Res Sci Technol Eng. 2015;4:1–8.

    Google Scholar 

  99. Shrivastava A, Gupta KM, Singhal KP, Shrivastava P. Extracellular release of non-peptide group compounds by antifungal bacillus and brevibacillus strains. Curr Bioact Compd. 2017;13:259–67. https://doi.org/10.2174/1573407212666160804124019.

    Article  CAS  Google Scholar 

  100. Nalini S, Inbakandan D, Venkatnarayanan S, Riyaz SM, Dheenan P, Vinithkumar N, et al. Pyrrolo isolated from marine sponge associated bacterium Halobacillus kuroshimensis SNSAB01–Antifouling study based on molecular docking, diatom adhesion and mussel byssal thread inhibition. Colloids Surf B Biointerfaces. 2019;173:9–17. https://doi.org/10.1016/j.colsurfb.2018.09.044.

    Article  CAS  PubMed  Google Scholar 

  101. Pawar R, Mohandass C, Dastager SG, Kolekar YM, Malwankar R. Antioxidative metabolites synthesized by marine pigmented Vibrio sp. and its protection on oxidative deterioration of membrane lipids. Appl Biochem Biotechnol. 2016;179:155–67. https://doi.org/10.1007/s12010-016-1985-z.

    Article  CAS  PubMed  Google Scholar 

  102. Balakrishnan D, Bibiana AS, Vijayakumar A, Santhosh RS, Dhevendaran K, Nithyanand P. Antioxidant activity of bacteria associated with the marine sponge Tedania anhelans. Indian J Appl Microbiol. 2015;55:13–18. https://doi.org/10.1007/s12088-014-0490-8.

    Article  CAS  Google Scholar 

  103. Ser H-L, Palanisamy UD, Yin W-F, Abd Malek SN, Chan K-G, Goh B-H, et al. Presence of antioxidative agent, pyrrolo [1, 2-a] pyrazine-1, 4-dione, hexahydro-in newly isolated Streptomyces mangrovisoli sp. nov. Front Microbiol. 2015;6:854 https://doi.org/10.3389/fmicb.2015.00854.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Yarkova M, Mokrov G, Gudasheva T, Seredenin S. Novel pyrrolo [1, 2-a] pyrazines (TSPO Ligands) with anxiolytic activity dependent on neurosteroid biosynthesis. Pharm Chem J. 2016;50:501–4. https://doi.org/10.1007/s11094-016-1476-0.

    Article  CAS  Google Scholar 

  105. Yarkov S, Mokrov G, Gudasheva T, Yarkova M, Seredenin S. Pharmacological study of new compounds acting as regulators of 18-kDa translocator protein ligands. Eksp Klin Farmakol. 2016;79:7–11. https://www.altmetric.com/details/7342427.

  106. Wang Y, Li S, Liu G, Li X, Yang Q, Xu Y, et al. Continuous production of algicidal compounds against Akashiwo sanguinea via a Vibrio sp. co-culture. Bioresour Technol. 2020;295:122246 https://doi.org/10.1016/j.biortech.2019.122246.

    Article  CAS  PubMed  Google Scholar 

  107. Manimaran M, Kannabiran K. Marine Streptomyces Sp. VITMK1 derived pyrrolo [1, 2-A] pyrazine-1, 4-dione, hexahydro-3-(2-methylpropyl) and its free radical scavenging activity. Open Bioact Compd J. 2017;5:23–30. https://doi.org/10.2174/1874847301705010023.

    Article  Google Scholar 

  108. Mitova M, Tutino ML, Infusini G, Marino G, De Rosa S. Exocellular peptides from Antarctic Psychrophile Pseudoalteromonas haloplanktis. Mar Biotechnol. 2005;7:523–31. https://doi.org/10.1007/s10126-004-5098-2.

    Article  CAS  Google Scholar 

  109. Ser H-L, Yin W-F, Chan K-G, Khan TM, Goh B-H, Lee L-H. Antioxidant and cytotoxic potentials of Streptomyces gilvigriseus MUSC 26T isolated from mangrove soil in Malaysia. Prog Biophys Mol Biol. 2018;1:a0000002 https://doi.org/10.1007/s10126-004-5098-2.

    Article  Google Scholar 

  110. Tangjitjaroenkun J. Evaluation of antioxidant, antibacterial and gas chromatography-mass spectrometry analysis of ethyl acetate extract of Streptomyces omiyaensis sch2. Asian J Clin Res. 2018;11:271–6.

    Article  Google Scholar 

  111. Li P-H, Zeng P, Chen S-B, Yao P-F, Mai Y-W, Tan J-H, et al. Synthesis and mechanism studies of 1, 3-benzoazolyl substituted pyrrolo [2, 3-b] pyrazine derivatives as nonintercalative topoisomerase II catalytic inhibitors. J Med Chem. 2016;59:238–52. https://doi.org/10.1021/acs.jmedchem.5b01284.

    Article  CAS  PubMed  Google Scholar 

  112. Trejo A, Arzeno H, Browner M, Chanda S, Cheng S, Comer DD, et al. Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase. J Med Chem. 2003;46:4702–13. https://doi.org/10.1021/jm0301787

    Article  CAS  PubMed  Google Scholar 

  113. Arya K, Tomar P, Singh J. Design, synthesis and biological evaluation of novel spiro [indole-pyridothiazine] analogs as antiproliferative agents. RSC Adv. 2014;4:3060–4. https://doi.org/10.1039/C3RA43908A.

    Article  CAS  Google Scholar 

  114. Mettey Y, Gompel M, Thomas V, Garnier M, Leost M, Ceballos-Picot I, et al. Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003;46:222–36. https://doi.org/10.1021/jm020319p.

    Article  CAS  PubMed  Google Scholar 

  115. Tun HW, Yoshimitsu T, Shigeoka D, Kamon T, Li Z, Qiu Y, et al. Substituted imidazo [4’, 5’: 4, 5] cyclopenta [1, 2-e] pyrrolo [1, 2-a] pyrazines and oxazolo [4’, 5’: 4, 5] cyclopenta [1, 2-e] pyrrolo [1, 2-a] pyrazines for treating brain cancer, in, Google Patents, 2016.

  116. Lu L, He C, Yao W Substituted pyrrolo [2, 3-b] pyrazines as FGFR inhibitors, in, Google Patents, 2017.

  117. Lu L, He C, Yao W Substituted pyrrolo [2, 3-b] pyrazines as FGFR inhibitors, in, Google Patents, 2016.

  118. Kumar KS, Kumar NP, Rajesham B, Kishan G, Akula S, Kancha RK. Silver-catalyzed synthesis of pyrrolopiperazine fused with oxazine/imidazole via a domino approach: evaluation of anti-cancer activity. N J Chem. 2018;42:34–38. https://doi.org/10.1039/C7NJ03608F.

    Article  Google Scholar 

  119. Lee YH, Lee JM, Kim SG, Lee YS. Synthesis and biological evaluation of 1, 2-dithiol-3-thiones and pyrrolo [1, 2-a] pyrazines as novel hypoxia inducible factor-1 (HIF-1) inhibitor. Bioorg Med Chem. 2016;24:2843–51. https://doi.org/10.1016/j.bmc.2016.04.054.

    Article  CAS  PubMed  Google Scholar 

  120. Seo Y, Lee JH, Park S-H, Namkung W, Kim I. Expansion of chemical space based on a pyrrolo [1, 2-a] pyrazine core: Synthesis and its anticancer activity in prostate cancer and breast cancer cells. Eur J Med Chem. 2020;188:111988 https://doi.org/10.1016/j.ejmech.2019.111988.

    Article  CAS  PubMed  Google Scholar 

  121. Dagar A, Seo Y, Namkung W, Kim I. A domino annulation approach to 3, 4-diacylpyrrolo [1, 2-a] pyrazines: decoration of pyrazine units. Org Biomol Chem. 2020;18:3324–33. https://doi.org/10.1039/D0OB00444H.

    Article  CAS  PubMed  Google Scholar 

  122. Johns BA, Kawasuji T, Taishi T, Taoda Y. Substituted 10-hydroxy-9, 11-dioxo-2, 3, 4a, 5, 9, 11, 13, 13a-octahydro-1h-pyrido [1, 2-a] pyrrolo [1′, 2′: 3, 4] imidazo [1, 2-d] pyrazine-8-carboxamides, in, Google Patents, 2015.

  123. Pitt GRW, Mayes PA, Andrau L. Substituted imidazo [1, 2-a] imidazo [4′, 5′: 4, 5] pyrrolo [1, 2-d] pyrazines for treating respiratory syncytial virus infections, in, Google Patents, 2016.

  124. Mitchell JP, PittG, Draffan AG, Mayes PA, Andrau L, Anderson KH. Substituted imidazo [1, 2-d] pyrrolo [1, 2-d] pyrazines for treating respiratory syncytial virus infections, in, Google Patents, 2017.

  125. Friedman M, Frank KE, Aguirre A, Argiriadi MA, Davis H, Edmunds JJ, et al. Structure activity optimization of 6H-pyrrolo [2, 3-e][1, 2, 4] triazolo [4, 3-a] pyrazines as JAK1 kinase inhibitors. Bioorg Med Chem Lett. 2015;25:4399–404. https://doi.org/10.1016/j.bmcl.2015.09.020.

    Article  CAS  PubMed  Google Scholar 

  126. Everitt S, Mortimore MP, Charrier J-D, MacCormick S, Storck P-H, Knegtel R, et al. Substituted pyrrolo [2, 3-B] pyrazines as ATR kinase inhibitors, in, Google Patents, 2015.

  127. Gangloff AR, Jennings AJ, Jones B, Kiryanov AA. Substituted pyrido [3, 2-e] pyrrolo [1, 2-a] pyrazines as inhibitors of poly (ADP-ribose) polymerase (PARP), in, Google Patents, 2015.

  128. Dorsch D, Buchstaller H-P, Moinet G, Wegener A Substituted pyrrolo [1, 2-a] pyrazin-1-ones and pyrazolo [1, 5-a] pyrazin-4-ones as inhibitors of tankyrase and poly (ADP-ribose) polymerase activity, in, Google Patents, 2015.

  129. Burdick D, Chen H, Wang S, Wang W. Substituted pyrrolo [2, 3-b] pyrazines as serine/threonine kinase inhibitors, in, Google Patents, 2016.

  130. Zhang Y, Liu H, Zhang Z, Wang R, Liu T, Wang C, et al. Discovery and biological evaluation of a series of pyrrolo [2, 3-b] pyrazines as novel FGFR inhibitors. Molecules. 2017;22:583 https://doi.org/10.3390/molecules22040583.

    Article  PubMed Central  Google Scholar 

  131. Jiang A, Liu Q, Wang R, Wei P, Dai Y, Wang X, et al. Structure-based discovery of a series of 5H-pyrrolo [2, 3-b] pyrazine FGFR kinase inhibitors. Molecules. 2018;23:698 https://doi.org/10.3390/molecules23030698

    Article  CAS  PubMed Central  Google Scholar 

  132. Ruah SSH, Kallel EA, Miller MT, Arumugam V, McCartney J, Anderson C, et al. Substituted spiro [piperidine-4, 1’-pyrrolo [1, 2-a] pyrazine] s as modulators of ion channels, in, Google Patents, 2016.

  133. Adcock C, Leblanc C. Substituted pyrrolo [2, 3-b] pyrazine compounds and their use, in, Google Patents, 2015.

  134. Prastya ME, Astuti RI, Batubara I, Takagi H, Wahyudi AT. Chemical screening identifies an extract from marine Pseudomonas sp.-PTR-08 as an anti-aging agent that promotes fission yeast longevity by modulating the Pap1–ctt1+ pathway and the cell cycle. Mol Biol Rep. 2020;47:33–43. https://doi.org/10.1007/s11033-019-05102-0.

    Article  CAS  PubMed  Google Scholar 

  135. Juneius CER, Jenisha E. Comparitive studies on the biocontrol efficiencies of wet biomass, dry biomass and secondary metabolites of pseudomonas fluorescence on Cnaphalocrocis medinalis. Int Res J Eng Technol. 2016;3:2518–30.

    Google Scholar 

  136. Tatipamula VB, Kolli MK, Lagu SB, Paidi KR, Reddy R, Yejella RP. Novel indolizine derivatives lowers blood glucose levels in Streptozotocin-induced diabetic rats: a histopathological approach. Pharm Rep. 2019;71:233–42. https://doi.org/10.1016/j.pharep.2018.11.004.

    Article  CAS  Google Scholar 

  137. Salimi F, Jafari‐Nodooshan S, Zohourian N, Kolivand S, Hamedi J. Simultaneous anti‐diabetic and anti‐vascular calcification activity of Nocardia sp. UTMC 751. Lett Appl Microbiol. 2018;66:110–7. https://doi.org/10.1111/lam.12833.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Fateme Dehnavi, Seyedeh Roya Alizadeh & Mohammad Ali Ebrahimzadeh

Authors
  1. Fateme Dehnavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seyedeh Roya Alizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Ali Ebrahimzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Ali Ebrahimzadeh.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dehnavi, F., Alizadeh, S.R. & Ebrahimzadeh, M.A. Pyrrolopyrazine derivatives: synthetic approaches and biological activities. Med Chem Res 30, 1981–2006 (2021). https://doi.org/10.1007/s00044-021-02792-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-021-02792-9

Keywords

Search

Navigation