110
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Synthesis of New Hexahydropyrimido[1,2-a]azepine Derivatives Bearing Functionalized Aryl and Heterocyclic Moieties As Anti-Inflammatory Agents

, ORCID Icon, ORCID Icon & ORCID Icon
Pages 625-641 | Received 22 Sep 2020, Accepted 02 Feb 2021, Published online: 24 Feb 2021

References

  • Soni JP , SenJ , ModhKM. Structure activity relationship studies of synthesised pyrazolone derivatives of imidazole, benzimidazole and benztriazole moiety for anti-inflammatory activity. J. Appl. Pharm. Sci.1(4), 115–120 (2011).
  • Charlier C , MichauxC. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur. J. Med. Chem.38(7–8), 645–659 (2003).
  • Beale JM , BlockJH. Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry (12th Edition).Lippincott Williams and Wilkins, PA, USA (2011).
  • Dannhardt G , KieferW. Cyclooxygenase inhibitors – current status and future prospects. Eur. J. Med. Chem.36(2), 109–126 (2001).
  • Penning TD , TalleyJJ , BertenshawSRet al. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, celecoxib). J. Med. Chem.40(9), 1347–1365 (1997).
  • Talley JJ . Selective inhibitors of cyclooxygenase-2 (COX-2). Prog. Med. Chem.36, 201–234 (1999).
  • Hla T , NeilsonK. Human cyclooxygenase-2 cDNA. Proc. Natl Acad. Sci. USA89(16), 7384–7388 (1992).
  • Limongelli V , BonomiM , MarinelliLet al. Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition. Proc. Natl Acad. Sci. USA107(12), 5411–5416 (2010).
  • Amir M , KumarH , KhanSA. Synthesis and pharmacological evaluation of pyrazoline derivatives as new anti-inflammatory and analgesic agents. Bioorg. Med. Chem. Lett.18(3), 918–922 (2008).
  • Venerito M , WexT , MalfertheinerP. Nonsteroidal anti-inflammatory drug-induced gastroduodenal bleeding: risk factors and prevention strategies. Pharmaceuticals (Basel)3(7), 2225–2237 (2010).
  • Wolfe MM , LichtensteinDR , SinghG. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N. Engl. J. Med.340(24), 1888–1899 (1999).
  • Burnier M . The safety of rofecoxib. Expert Opin. Drug Saf.4(3), 491–499 (2005).
  • Wong D , WangM , ChengY , FitzgeraldGA. Cardiovascular hazard and non-steroidal anti-inflammatory drugs. Curr. Opin. Pharmacol.5(2), 204–210 (2005).
  • Samuelsson B . Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science220(4597), 568–575 (1983).
  • Hermecz I , MeszarosZ. Advances in Heterocyclic Chemistry (1st Edition).John Wiley & Sons, NJ, USA (1983).
  • Nikitin SV , SmirnovLD. Synthesis, chemical and biological properties of pyrido[1,2-a]pyrimidines. Chem. Heterocycl. Compd.30(5), 507–522 (1994).
  • Hermecz I , MészárosZ. Pyrido[1,2-a]pyrimidines; new chemical entities in medicinal chemistry. Med. Res. Rev.8(2), 203–230 (1988).
  • Hermecz I , BreiningT , SimonK , Erös-TakácsyT , PodányiB , SessiJ. Nitrogen bridgehead compounds. Part 80. Unusual reaction of ethyl 9-bromo-4-oxo-6,7,8,9-tetrahydro-4h-pyrido[1,2-a]pyrimidine-3-carboxylates and N-methylaniline. J. Heterocycl. Chem.28(5), 1405–1411 (1991).
  • Hassanein HH , AbdelHakim G. Synthesis of some diazabicyclic compounds of expected non-narcotic analgesic activity. Bull. Fac. Pharm. Cairo Univ.36(2), 1–9 (1998).
  • El-Sayed NA , AwadallahFM , IbrahimNA , El-SaadiMT. Potential anti-inflammatory activity and ulcerogenicity study of some novel pyrimido[4′,5′:4,5]pyrimido[1,6-a]azepine derivatives. Med. Chem. Res.21, 395–405 (2012).
  • Arafa RK , NourMS , El-SayedNA. Novel heterocyclic-fused pyrimidine derivatives: synthesis, molecular modeling and pharmacological screening. Eur. J. Med. Chem.69, 498–507 (2013).
  • El-Sayed NA , AwadallahFM , IbrahimNA , El-SaadiMT. Synthesis, anti-inflammatory and ulcerogenicity studies of some substituted pyrimido[1,6-a]azepine derivatives. Eur. J. Med. Chem.45(7), 3147–3154 (2010).
  • Tiperciuc B , PârvuA , TamaianR , NastasăC , IonuţI , OnigaO. New anti-inflammatory thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles with antioxidant properties as potential iNOS inhibitors. Arch. Pharm. Res.36(6), 702–714 (2013).
  • Omar TN . Synthesis of Schiff bases of benzaldehyde and salicylaldehyde as anti-inflammatory agents. Iraqi J. Pharm. Sci.16(2), 5–11 (2007).
  • Bhandari SV , BotharaKG , RautMK , PatilAA , SarkateAP , MokaleVJ. Design, synthesis and evaluation of antiinflammatory, analgesic and ulcerogenicity studies of novel S-substituted phenacyl-1,3,4-oxadiazol-2-thiol and Schiff bases of diclofenac acid as nonulcerogenic derivatives. Bioorg. Med. Chem.16(4), 1822–1831 (2008).
  • Sridhar SK , RameshA. Synthesis and pharmacological activities of hydrazones, Schiff and Mannich bases of isatin derivatives. Biol. Pharm. Bull.24(10), 1149–1152 (2001).
  • Goddard CJ . Anti-inflammatory 1-phenylpyrazole-4-heteroarylalkanoic acids. J. Heterocycl. Chem.28(6), 1607–1612 (1991).
  • Rajak H , VeerasamyR , KharyaM , MishraP. Design, synthesis, and pharmacological evaluation of novel oxadiazole and oxadiazoline analogs as anti-inflammatory agents. J. Enzyme Inhib. Med. Chem.25(4), 492–501 (2010).
  • Nampurath G , DurgashivaprasadE , MathewG , SebastianS , ReddySAM , MudgalJ. Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs. Indian J. Pharmacol.46(5), 521–527 (2014).
  • Majumdar P , PatiA , PatraM , BeheraRK , BeheraAK. Acid hydrazides, potent reagents for synthesis of oxygen-, nitrogen-, and/or sulfur-containing heterocyclic rings. Chem. Rev.114(5), 2942–2977 (2014).
  • Fahmy AMF , Abdel-HamidHA , YousefMegally Abdo N. Uses of isothiocyanate as building block in syntheses of triazole, thiadiazole, quinazoline, and pyrimidine systems of agrochemical and biological activities. Egypt. J. Chem.58(6), 645–657 (2015).
  • Winter CA , RisleyEA , NussGW. Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Exp. Biol. Med.111(3), 544–547 (1962).
  • Selinsky BS , GuptaK , SharkeyCT , LollPJ. Structural analysis of NSAID binding by prostaglandin H2 synthase: time-dependent and time-independent inhibitors elicit identical enzyme conformations. Biochemistry40(17), 5172–80 (2001).
  • Kurumbail RG , StevensAM , GierseJKet al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature384(6610), 644–648 (1996).
  • SwissADME . Drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep7(42717), (2017).
  • Daina A , MichielinO , ZoeteV. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep.7(1), 42717 (2017).
  • Daina A , ZoeteV. A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem.11(11), 1117–1121 (2016).
  • Koekoesi J , HermeczI , MeszarosZet al. 2-oxo-2,6,7,8,9,10 hexahydro-pyrimido[1,2-a]azepines and antianginal method of use thereof and of 4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepines. US19800148234 19800509 (1983). https://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=4404205&KC=&FT=E&locale=en_EP
  • Kökösi J , SzászG , HermeczI , MészárosZ , Csákvári-PongorM , TóthG. Nitrogen bridgehead compounds. Part 19. Synthesis of polymethylenepyrimidin-4-ones. J. Heterocycl. Chem.19(4), 909–912 (1982).
  • Hassanein HH , GeorgeyHH , FouadMA , ElKerdawy AM , SaidMF. Synthesis and molecular docking of new imidazoquinazolinones as analgesic agents and selective COX-2 inhibitors. Future Med. Chem.9(6), 553–578 (2017).
  • Hassib ST , HassanGS , El-zaherAA , FouadMA , El-ghafarOAA , TahaEA. Synthesis and biological evaluation of new prodrugs of etodolac and tolfenamic acid with reduced ulcerogenic potential. Eur. J. Pharm. Sci.140, 105101 (2019).
  • Knights KM , MangoniAA , MinersJO. Defining the COX inhibitor selectivity of NSAIDs: implications for understanding toxicity. Expert Rev. Clin. Pharmacol.3(6), 769–776 (2010).
  • Rieke CJ , MulichakAM , GaravitoRM , SmithWL. The role of arginine 120 of human prostaglandin endoperoxide H synthase-2 in the interaction with fatty acid substrates and inhibitors. J. Biol. Chem.274(24), 17109–14 (1999).
  • Warner TD , MitchellJA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J.18(7), 790–804 (2004).
  • Kozak KR , CrewsBC , MorrowJDet al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J. Biol. Chem.277(47), 44877–44885 (2002).
  • Garavito RM , DeWittDL. The cyclooxygenase isoforms: structural insights into the conversion of arachidonic acid to prostaglandins. Biochim. Biophys. Acta1441(2–3), 278–287 (1999).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.