YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

The Correlation Between Conformations and Activities of ${\omega}$-Pyridylalkenoic Acids

${\omega}$-피리딜 알켄산의 형태와 활성간의 상관관계

  • Rhee, Jong-Dal (Department of Pharmacy, College of Pharmacy, Yeungnam University) ;
  • Doh, Seong-Tak (Department of Clinical Pathology, Taegu Junior Health College)
  • 이종달 (영남대학교 약학대학 약학과) ;
  • 도성탁 (대구보건전문대학 임상병리과)
  • Published : 1997.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Molecular mechanics and conformation search methods were carried oyt to investigate the relationship between conformations and thromboxane synthetase ingibitory activities of om ega-pyridylalkenoic acids. The initial geometries of ${\omega}$-pyridylalkenoic acids and heme part of cytochrome P-450 were obtained from MM+ geometry optimization. The bond lenths and angles were not varied by step during the conformation searching. Stable conformers of some ${\omega}$-pyridylalkenoic acids were obtained by comformational search method. The distances were 8.5~10.8 ${\AA}$- between N atom at 3-position of pyridine ring and C atom at carboxylic group of stable ${\omega}$-pyridylalkenoic acids. The conformations of ${\omega}$-pyridylalkenoic acids and heme part complex were determined by same method. In theses structures, benzene ring and ethylene group in ${\omega}$-pyridylalkenoic acids are making the structure more rigid and increase inhbitory activity. The electron donating groups in C atom shich is connected to pyridine ring also increase activity.

Keywords

References

  1. Proc. Natl. Acd. Sci. U.S.A. v.74 Application of limidazole as a selective inhibitor of thromboxane synthetase in human platelets Needleman, P.;Raz, A.;Ferrendelli, J. A.;Minkes, M.
  2. Thromb. Res. v.20 Effects of a selective inhibitors of thromboxane synthetase on human blood platelet behaviour Heptinstall, S.;Bevan, J.;Cockbill, S. R.;Hanley, S. P.;Parry, M. J.
  3. J. Med. Chem. v.24 Highly selective inhibition of thromboxane synthetase 1. Imidazole derivatives Iizuka, K.;Akahane, K.;Momose, D.;Nakazawa, M.;Tanouchi, T.;Kawamura, M.;Ohyama, I.;Kajiwara, I.;Iguchi, Y.;Okada, T.;Taniguchi, K.;Miyamoto, T.;Hayashi, M.
  4. J. Med. Chem. v.24 Highly selective inhibition of thromboxane synthetase 2. Pyridine Derivatives Tanouchi, T.;Kawamura, M.;Ohyama, I.;Kajiwara, I.;Iguchi, Y.;Okada, T.;Iizuka, K.;Nakazawa, M.
  5. J. Cardiovasc. Pharmacol v.5 Responsiveness of platelets and coronary ateries from different species to synthetic thromboxane and prostaglandin endoper-oxide analogs Burke, S. E.;DiCola, G.;Lefer, M. A.
  6. Tetrahedron Lett. v.24 Synthesis of a new series of potent inhibitors of thromboxane A₂biosynthesis Corey, E. J.;Pyne, S. G.;Schafer, A. I.
  7. Annu. Rep. Med. Chem. v.22 Thromboxane Synthase inhibitors and antagoist Cross, P. E.;Dickinson, R. P.
  8. J. Med. Chem. v.37 6.6-Disubstituted Hex-5-enoic Acid Derivaties as Combined Thromboxane A₂Receptor Antagonists and Synthetase Inhibitors Soyka, R.;Heckel, A.;Nickel, J.;Eisert, W.;Mller, T. H.;Weisenberger, H.
  9. J. Med. Chem. v.28 Thromboxane synthetase inhibitor (TXSI) design, synthesis, and evaluation of a novel series of ω-pyridylalkenoic acid Kato, K.;Ohkawa, S.;Terashita, Z.;Nishikawa, K.
  10. Adv. Prostaglandins, Thromboxane, Leukotriene Res. v.11 Thromboxane synthase as a cytochrome P450 enzyme Ullrich, V.;Haurand, M.
  11. J. Mol. Biol. v.153 Conformation Change of Cytochrome c II. Ferricytochrome c Refinement at 1.8 and Comparision with the Ferricytochrome Structure Takano, T.;Dickerson, R. F.
  12. J. Biochem. v.92 Interaction of polycyclic hydrocarbons with cytochrome P-450 III. Effects of hydrocarbon binding on the interaction of some ligands with P-450 heme Imai, Y.
  13. HyperChem Package
  14. Am. Chem. Soc. Molecular Mechanics, ACS Monograph 177 Burket, U.;Allinger, N. L.