Skip to main content
SpringerLink
Log in

Synthesis and antiviral study of 4-(7,7-dimethyl-4-(piperazin-1-yl)-5,6,7,8-tetrahydroquinazolin-2-yl) morpholine derivatives

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

A series of 4-(7,7-dimethyl-4-(piperazin-1-yl)-5,6,7,8-tetrahydroquinazolin-2-yl)morpholine substituted sulfonamide and urea derivatives has been synthesized and characterized using spectral techniques. The antiviral activity of these compounds against an avian paramyxo virus (AMPV-1) was screened using MTT assay and found that one of the sulfonamide derivatives (2d) show three-fold higher antiviral activity than Ribavirin, a commercial antiviral drug substance.

Graphical abstract

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
Scheme 1
Scheme 2

Similar content being viewed by others

References

  • Cano C, Barbeau OR, Bailey C, Cockcroft XL, Curtin NJ, Duggan H, Frigerio M, Golding BT, Hardcastle IR, Hummersone MG, Knights C, Menear KA, Newell DR, Richardson CJ, Smith GCM, Spittle B, Griffin RJ (2010) DNA-dependent protein kinase (DNA-PK) inhibitors. Synthesis and biological activity of quinolin-4-one and pyridopyrimidin-4-one surrogates for the chromen-4-one chemotype. J Med Chem 53(24):8498–8507

    Article  CAS  PubMed  Google Scholar 

  • Cano C, Saravanan K, Bailey C, Bardos J, Curtin NJ, Frigerio M, Golding BT, Hardcastle IR, Hummersone MG, Menear KA, Newell DR, Richardson CJ, Shea K, Smith GC, Thommes P, Ting A, Griffin RJ (2013) 1-Substituted (dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed with dual DNA-PK/PI3-K inhibitory activity. J Med Chem 56(16):6386–6401

  • Chou T, Li K, Frankowski KJ, Schoenen FJ, Deshaies RJ (2013) Structure–activity relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase. Chem Med Chem 8(2):297–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Boer D, Bosman IJ, Hidvegi E, Manzoni C, Benko AA, dos Reys LJ, Maes RA (2001) Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market. Forensic Sci Int 121(1-2):47–56

    Article  PubMed  Google Scholar 

  • Dibyendu D, Khanna IK, Pillarisetti S (2010) Novel bicyclic compounds as GATA modulators. WO028174(A1):1–135

  • Dmitriy Z, Peter P (2012) Oncolytic newcastle disease virus for cancer therapy: old challenges and new directions. Future Microbiol 7(3):347–367

    Article  Google Scholar 

  • Fackler JC, Flannery K, Zipkin M, McIntosh K (1990) Precautions in the use of ribavirin at the children’s hospital. N Engl J Med 322(9):634

    CAS  PubMed  Google Scholar 

  • Gerlier D, Thomasset N (1986) Use of MTT colorimetric assay to measure cell activation. J Immunol Methods 94(1-2):57–63

    Article  CAS  PubMed  Google Scholar 

  • Gilbert BE, Knight V (1986) Biochemistry and clinical applications of ribavirin. Antimicrob Agents Chemother 30:201–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hebert MF, Guglielmo BJ (1990) What is the clinical role of aerosolized ribavirin? Drug Intell Clin Pharm 7-8:735–738

    Google Scholar 

  • Hepworth JD, Gabbutt CD, Heron BM (Eds.) (1995) Comprehensive heterocyclic chemistry-II. Pergamon Press, Oxford, p 221

    Google Scholar 

  • Izuru A, Tsuyoshi A, Naoki O, Yukiyo T, Kazuyuki S, Hiroyuki A, Masafumi K, Toru N (2012) Preclinical characterization of JTK-853, a novel nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. Antimicrob Agents Chemother 56(8):4250–4256

    Article  Google Scholar 

  • John RK, Huaqing L, Irene D, David GW, Tracy LC, Arlene MM, Lvan M, Marina IS, Thomas RM, Timothy AE, Jorge DB, Marlon C (2010) Rigidified 2-aminopyrimidines as histamine H4 receptor antagonists: effects of substitution about the rigidifying ring. Biorg Med Chem Lett 20(6):1900–1904

    Article  Google Scholar 

  • Joule JA, Mills K (2008) Heterocyclic chemistry. Wiley, New York, NY

    Google Scholar 

  • Katritzky AR, Rees CW, Hepworth JD (Eds.) (1985) Comprehensive heterocyclic chemistry. Pergamon Press, Oxford, p 150

    Google Scholar 

  • Kengi M, Takashi S, Takao N, Michio I, Neill AG, Jin-Chen Y, Shogi O, Yuji N (2003) Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. Part 4: structure–activity relationships for substituents on the quinazoline moiety of 4-[4-(N-substituted(thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives. Biorg Med Chem Lett 13(18):3001–3004

    Article  Google Scholar 

  • Kobayashi J, Kand F, Ishibashi M, Shigemori H (1991) Manzacidins A–C, novel tetrahydropyrimidine alkaloids from the Okinawan marine sponge hymeniacidon sp. J Org Chem 56(14):4574–4576

    Article  CAS  Google Scholar 

  • Looper RE, Runnegar MTC, Williams RM (2005) Synthesis of the putative structure of 7-deoxycylindrospermopsin: C7 oxygenation is not required for the inhibition of protein synthesis. Angew Chem Int Ed 25(44):3879–3881

    Article  Google Scholar 

  • Noronha G, Cao J, Gritzen C, Mak C, McPherson A, Pathak VP, Renick J, Soll RM, Zeng B, Dneprovskaia E (2008) 2-amino-5-substituted pyrimidine inhibitors. US Patent 0027070:1–99

    Google Scholar 

  • Ravindra PV, Ashok KT, Bhaskar S, Chauhan RS (2009) Newcastle disease virus as an oncolytic agent. Indian J Med Res 130:507–513

    CAS  PubMed  Google Scholar 

  • Scozzafava A, Owa T, Mastrolorenzo A, Supuran CT (2003) Anticancer and antiviral sulfonamides. Curr Med Chem 10(11):925–953

    Article  CAS  PubMed  Google Scholar 

  • Sekiya T, Hiranuma H, Kanayama T, Hata S (1980) Pyrimidine derivatives I. Synthesis of hypoglycemic 2-piperazino-5,6-polymethylenepyrimidines 5,6-polymethylenepyrimidines. Eur J Med Chem 15(4):317–322

    CAS  Google Scholar 

  • Selvakumar B, Vaidyanathan SP, Madhuri S, Elango KP (2017) Synthesis and antiviral activity of 4-(7,7-dimethyl-4-[4-{N-aroyl/benzyl}1-piperazinyl]-5,6,7,8-tetrahydroquinazolin-2-yl) morpholine derivatives. Arkivoc iv:353–364

  • Skinner GS, Wunz PR (1951) 2,5,5-Trialkyl-1,4,5,6-tetrahydropyrimidines. J Am Chem Soc 73(8):3814–3815

    Article  CAS  Google Scholar 

  • Sudhakar Babu K, Ravindranath KL, Latha J, Prabhakar V (2015) Synthesis, characterization and mass analysis of novel tri substituted quinazoline-urea derivatives bearing trans substituted morpholine and azetidinone moieties. Int J Pharm Res Rev 4(1):364–380

    Google Scholar 

  • Supuran CT, Innocenti A, Mastrolorenzo A, Scozzafava A (2004) Antiviral sulfonamide derivatives. Mini Rev Med Chem 4(2):189–200

    Article  CAS  PubMed  Google Scholar 

  • Suresh Kumar K, Swastika G, Ravichandran V, Vijayapandi P (2014) Synthesis, antiviral and antimicrobial activities of quinazoline urea analogs. Int J Drug Des Discov 4(4):1215–1230

    Google Scholar 

  • Tetsuo S, Hidetoshi H, Masayuki U, Shunsuke H, Shun-Ichi Y (1981) Pyrimidine deivatives II. New synthesis and reactions of 4-amino-2-methylthiopyrimidine derivatives. Chem Pharm Bull 29(4):948–954

    Article  Google Scholar 

Download references

Acknowledgements

We are thankful to the Management, Anthem Biosciences, Bangalore, India, for their invaluable support and allocation of resources for this work. We would like to thank the Analytical Chemistry team of Anthem Biosciences for having carried out all the analytical work.

Author information

Authors and Affiliations

  1. Anthem Biosciences Pvt. Ltd., Bangalore, 560 099, India

    Balaraman Selvakumar

  2. National Institute of Animal Biotechnology, Hyderabad, 500 049, India

    Naveen Gujjar & Madhuri Subbiah

  3. Department of Chemistry, Gandhigram Rural Institute (Deemed University), Gandhigram, 624 302, India

    Kuppanagounder P. Elango

Authors
  1. Balaraman Selvakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naveen Gujjar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Madhuri Subbiah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kuppanagounder P. Elango
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kuppanagounder P. Elango.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Selvakumar, B., Gujjar, N., Subbiah, M. et al. Synthesis and antiviral study of 4-(7,7-dimethyl-4-(piperazin-1-yl)-5,6,7,8-tetrahydroquinazolin-2-yl) morpholine derivatives. Med Chem Res 27, 512–519 (2018). https://doi.org/10.1007/s00044-017-2077-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-017-2077-5

Keywords

Search

Navigation