Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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Ligand Design of 5,5'-Diphenylimidazolidine-2,4-dione Analogues as A New Class of Potent Inhibitors of Fatty Acid Amide Hydrolase

새로운 Fatty Acid Amide Hydrolase 저해제로서 5,5'-Diphenylimidazolidine-2,4-dione 유도체의 리간드 설계

  • Cho, Jong-Un (Division of Applied Biologies and Chemistry, College of Agriculture and Life Science, Chungnam National University) ;
  • Soung, Min-Gyu (Division of Applied Biologies and Chemistry, College of Agriculture and Life Science, Chungnam National University) ;
  • Sung, Nack-Do (Division of Applied Biologies and Chemistry, College of Agriculture and Life Science, Chungnam National University)
  • 조종운 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 성민규 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부)
  • Published : 2008.06.30
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Abstract

3D-QSARs (3 dimensional quantitative structrue-activity relationships) on the inhibition activities of 3-substituted-5,5'-diphenylimidazolidine-2,4-dione derivatives (1-22) against FAAH (fatty acid amide hydrolase) were studied quantitatively using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indice analysis) methods. The statistical results of the CoMFA 1A and CoMSIA 2F model are better predictability and fitness. And also, the designed X=I, Y=$N_{2}^{+}$-substituent (P1: $Pred.pI_{50}$=6.55), according to the contour maps with information of the two models, showed the most inhibition activity against FAAH.

3-치환된 5,5'-diphenylimidazolidine-2,4-dione 유도체(1-22)들의 fatty acid amide hydrolase (FAAH) 저해활성에 관한 3차원적인 정량적 구조와 활성과의 관계(3D-QSARs)를 비교 분자장 분석(CoMFA)과 비교분자 유사성 지수분석(CoMFA) 방법으로 각각 검토하였다. CoMFA A1 모델과 CoMSIA 2F 모델 모두 상관성과 예측성이 양호하였다. 두 모델의 정보에 의한 등고도에 따라 설계된 X=I, Y=$N_2{^+}$-치환체(P1: $Pred.pI_{50}$=6.55)는 FAAH에 대하여 가장 높은 저해활성을 나타내었다.

Keywords

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