Archives of Pharmacal Research

  • 제24권4호
  • /
  • Pages.270-275
  • /
  • 2001
  • /
  • 0253-6269(pISSN)
  • /
  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

4-Hydroxy-6-Oxo-6,7-Dihydro-Thieno[2,3-b] Pyrimidine Derivatives : Synthesis and Their Biological Evaluation for the Glycine Site Acting on the N-Methyl-D-Aspartate (NMDA) Receptor

  • Hwang, Ki-Jun (Department of Chemistry and Research Center of Bioactive Materials, College of Natural Science) ;
  • Lee, Tae-Suk (Department of Chemistry and Research Center of Bioactive Materials, College of Natural Science) ;
  • Kim, Ki-Won (Department of Pharmacology, College of Medicine , Chunbuk National University) ;
  • Kim, Beam-Tae (Department of Chemistry and Research Center of Bioactive Materials, College of Natural Science) ;
  • Lee, Chul-Min (Department of Chemistry and Research Center of Bioactive Materials, College of Natural Science) ;
  • Park, Eun-Young (Department of Pharmacology, College of Medicine , Chunbuk National University) ;
  • Woo, Ran-Sook (Department of Pharmacology, College of Medicine , Chunbuk National University)
  • 발행 : 2001.08.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Bioisostere approach has been shown to be useful to augment potency or to modify certain physiological properties of a lead compound. Based upon well documented bioisosterism, an isosteric replacement of benzene ring of 4-hydroxy-2-quinolone compound (L-695902) with a thiophene moiety was carried out to prepare the title compounds, 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidines 15. The resulting bioisosteric compounds 15 were evaluated for their antagonistic activity (birding assay) for NMDA receptor glycine site.

키워드

참고문헌

  1. J. Med. Chem. v.42 Thieno[3,2-b]-and Thieno[2,3-b]pyrrole Bioisosteric Analogues of the Hallucinogen and Serotonin Agonist N,N-Dimethyltryptamine Blair,J.B.;Kanthasamy,A.;Lucaites,V.L.;Nelson,D.L.;Nichols,D.E.
  2. J. Med. Chem. v.40 Structure-activity relationships of alkyl-and alkoxy-substituted 1,4-dihydroquinoxaline-2,3-diones: Potent and systemically active antagonists for the glycine site of the NMDA receptor Cai,S.X.;Kher,S.M.;Zhou,Z.L.;Ilyin,V.;Espitia,S.A.;Tran,M.;Hawkinson,S.E.;Woodward,R.M.;Weber,E.;Keana,J.F.
  3. Biomed. Chem. Lett. v.3 Synthesis and excitatory Amino acid pharmacology of some novel quinoxalinediones Epperson,J.R.;Hewawasam,P.;Meanwell,N.A.;Boissard,C.G.;Gribkoff,V.K.;Postmunson,D.
  4. J. Med. Chem. v.40 Substituted indole-2-carboxylates as in vivo potent antagonists acting as the strychnine-insensitive glycine binding site Fabio,R.D.;Capelli,A.M.;Conti,N.;Cugola,A.;Donati,D.;Feriani,A.;Gastaldi,P.;Gaviraghi,G.
  5. Science v.241 Quinoxalinediones: Potent competitive non-NMDA glutamate receptor antagonists Honore,T.;Davies,S.N.;Drejer,J.;Fletcher,E.J.;Jacobsen,P.;Lodge,D.;Nielsen,F.E.
  6. Bull. Korean. Chem. Soc. v.12 A Facile Synthesis of 2-Aminothiophene Derivatives Hwang,K.J.;Choi,N.K.
  7. NMDA Receptor(2nd ed.) Noncompetitive NMDA antagonists as drugs Iversen,L.L.;Kemp,J.A.;Collingridge,G.L.(ed.);Watkins,J.C.(ed.)
  8. Nature v.325 Glycine potentiates the NMDA response in cultured mouse brain neurons Johnson,J.W.;Ascher,P.
  9. J. Med. Chem. v.31 Excitatory amino acid Neurotransmission Johnson,R.L.;Koerner,K.F.
  10. Trends pharmacol. Sci. v.14 The glycine site of the NMDA receptor Kemp,J.A.;Leeson,P.D.
  11. J. Med. Chem. v.37 Tricklebank, M. D. 3'-(Arylmethyl-and 3'-(Aryloxy)-3-phenyl-4-hydroxyquinolin-2(1H)-ones:Orally Active Antagonists of the Glycine Site on the NMDA Receptor Kulagowski,J.J.;Baker,R.;Cirtis,N.R.;Leeson,P.D.;Mawer,I.M.;Moseley,A.M.;Ridgill,M.P.;Rowley,M.;Stansfield,I.;Foster,A.C.;Gromwood,S.;Hill,R.G.;Kemp,J.A.;Marshall,G.R.;Saywell,K.L.
  12. Exp. Opin.Ther. Pat. v.6 Glycine-site NMDA receptor antagonists: An update Kulagowski,J.J.
  13. J. Med. Chem. v.34 Kynurenic acid derivatives. Structure-activity relationships for excitatory amino acid antagonism and identification of potent and selective antagonists at the glycine site on the NMDA receptor Leeson,P.D.;Baker,R.;Carling,R.W.;Curtis,N.R.;Moore,K.W.;William,B.J.;Foster,A.C.;Donald,A.E.;Kemp,J.A.;Marshall,G.R.
  14. J. Med. Chem. v.35 4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor Leeson,P.D.;Carling,R.W.;Moore,K.W.;Moseley,A.M.;Smith,G.D.;Stevenson,G.;Chan,T.;Baker,R.;Foster,A.C.;Grimwood,S.;Kemp,G.A.;Marshall,G.R.;Hoogsteen,K.
  15. J. Med. Chem. v.37 The glycine site on the NMDA receptor: Structure-activity relationship and therapeutic potential Leeson,P.D.;Iversen,L.L.
  16. J. Med. Chem. v.35 3-Phenyl-4-hydroxy-2-quinolin-2(1H)-ones: Potent and Selective antagonists at the strychnine-insensitive glycine site on the NMDA receptor complex McQuaid,L.A.;Smith,E.C.R.;Lodge,D.;Pralong,E.;Wikel,J.H.;Calligaro,D.O.
  17. J. Clin. Parmaco. v.34 Excitatory amino acids antagonists and their potential for the treatment of ischaemic brain damage in man McCullough,J.
  18. Cerebrovasc. Brain Metab. Rev. v.2 Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission Meldrum,B.
  19. Annu. Rev. Phamacol. Toxicol. v.29 The Excitatory Amine acid Receptor; Their Classes, Pharm-acology and Distinct properties in the Function of the Central Nerveous System Monagham,D.T.;Bridges,R.J.;Cotman,C.W.
  20. Trends Neurosci. v.10 Excitotoxicity and the NMDA receptor Rothman,S.M.;Olney,J.W.
  21. J. Med. Chem. v.36 3-Acyl-4-hydroxy-quinolin-2(1H)-ones. Systemically Active Anticonvulsants Acting by Antagonism at the Glycine Site of the N-Methyl-D-aspartate Receptor Complex Rowley,M.;Leeso,P.D.;Stevenson,G.I.;Moseley,A.M.;Stansfield,I.;Sanderson,I.;Robinson,L.;Baker,R.;Kemp,J.A.;Marshall,G.R.;Foster,A.C.;Grimwood,S.;Tricklebank,M.D.;Saywell,K.L.
  22. J. Med. Chem. v.35 3-(2-carboxyindol-3-yl)propionic acid-based antagonists of the NMDA receptor associated glycine binding site Salituro,F.G.;Harrison,B.L.;Baron,B.M.;Nyce,P.L.;Stewart,K.T.;Kehne,J.H.;White,H.S.;McDonald,I.A.
  23. The Organic Chemistry of Drug Design and Drug Action Silverman,R.B.