Structure-based de novo design, synthesis, and biological evaluation of the indole-based PPARγ ligands (I)

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 22, 2006, Pages 5913-5916

  Dong, Xiaochun ^a   Zhang, Zhenshan ^b   Wen, Ren ^a   Shen, Jianhua ^b   Shen, Xu ^b   Jiang, Hualiang ^b  

^a FUDAN UNIVERSITY   (China)

^b SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

De novo drug design; Indole compounds; PPAR ligand; Type II diabetes

Indexed keywords

INDOLE DERIVATIVE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; RAGAGLITAZAR; ROSIGLITAZONE;

ARTICLE; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG DESIGN; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; PROTEIN BINDING; STRUCTURE ACTIVITY RELATION;

ALGORITHMS; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; HUMANS; HYDROGEN BONDING; INDOLES; LIGANDS; PPAR GAMMA; PROTEIN BINDING; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLIDINEDIONES;

EID: 33749252746     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.06.093     Document Type: Article

References (14)

1. Bogacka I., Xie H., Bray G.A., and Smith S.R. Diab. Care 27 (2004) 1660
2. Momose Y., Meguro K., Ikeda H., Hatanaka C., Oi S., and Sohda T. Chem. Pharm. Bull. 39 (1991) 1440
3. Cantello B.C.C., Cawthorne M.A., Cottam G.P., Du P.T., Haigh D., Hindley R.M., Lister C.A., Smith S.A., and Thurlby P.L. J. Med. Chem. 37 (1994) 3977
4. Henke B.R. J. Med. Chem. 47 (2004) 4118
5. Lohray B.B., Lohray V.B., Bajji A.C., Kalchar S., Poondra R.R., Padakanti S., Chakrabarti R., Vikramadithyan R.K., Misra P., Juluri S., Mamidi N.V.S.R., and Rajagopalan R. J. Med. Chem. 44 (2001) 2675
6. Henke B.R., Blanchard S.G., Brackeen M.F., Brown K.K., Cobb J.E., Collins J.L., Harrington W.W., Hashim M.A., Hull-Ryde E.A., Kaldor I., Kliewer S.A., Lake D.H., Leesnitzer L.M., Lehmann J.M., Lenhard J.M., Orband-Miller L.A., Miller J.F., Mook R.A., Noble S.A., Oliver W., Parks D.J., Plunket K.D., Szewczyk J.R., and Willson T.M. J. Med. Chem. 41 (1998) 5020
7. James F.D., Akiyama T., Einstein M., Habulihaz B., Doebber T., Berger J.P., Meinke P.T., and Shi G.Q. Bioorg. Med. Chem. Lett. 15 (2005) 5035
8. Henke B.R., Adkisom K.K., Blanchard S.G., Leesnitzer L.M., Mook R.A., Plunket J.K.D., Ray J.A., Roberson C., Unwalla R., and Willson T.M. Bioorg. Med. Chem. Lett. 9 (1999) 3329
9. All molecular modeling and docking simulations were performed on a Silicon Graphics Origin3200 workstation using the SYBYL 6.8 molecular modeling software from Tripos Inc. and Insight II 2000 molecular modeling software from Accelrys Inc.
10. Nolte R.T.G., Wisely B., Westin S., Cobb J.E., Lambert M.H., Kurokawa Ri., Rosenfeld M.G., Willson T.M., Glass C.K., and Milburn M.V. Nature 395 (1998) 137
11. The ligand-binding pocket of the receptor was defined as the collection of the amino acids enclosed within a sphere of 5 Å radius around the bound ligand.
12. MCSS calculations were performed using the CHARMM 22 force field and InsightII/MCSS 2.1program.
13. The docking parameters were set on as follow: not only the atom types but also the generations and the number of runs for the LGA algorithm were edited and properly assigned according to the requirement of the Amber force field. The number of generation, energy evaluation, and docking runs was set to 370,000, 1,500,000, and 10, respectively. The kinds of atomic charges were taken as Kollman-all-atom for PPARγ and Gasteiger-Huckel for ligands.
14. Yu C.Y., Chen L.L., Luo H.B., Chen J., Cheng F., Gui C.S., Zhang R.H., Shen J.H., Chen K.X., Jiang H.L., and Shen X. Eur. J. Biochem. 271 (2004) 386