Tags

Type your tag names separated by a space and hit enter

3D QSAR studies on T-type calcium channel blockers using CoMFA and CoMSIA.
Bioorg Med Chem. 2004 Apr 01; 12(7):1613-21.BM

Abstract

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of isoxazolyl compounds as a potent T-type calcium channel blockers. A set of 24 structurally similar compounds served to establish the model. Four different conformations of the most active compound were used as template structures for the alignment, three of which were obtained from Catalyst pharmacophore modeling and one by using SYBYL random search option. All CoMFA and CoMSIA models gave cross-validated r(2) (q(2)) value of more than 0.5 and conventional r(2) value of more than 0.85. The predictive ability of the models was validated by an external test set of 10 compounds, which gave satisfactory pred r(2) values ranging from 0.577 to 0.866 for all models. Best predictions were obtained with CoMFA std model of Conformer no: 3 alignment (q(2)=0.756, r(2)=0.963), giving predictive r(2) value of 0.866 for the test set. CoMFA and CoMSIA contour maps were used to analyze the structural features of the ligands accounting for the activity in terms of positively contributing physicochemical properties: steric, electrostatic, hydrophobic and hydrogen bonding fields.

Authors+Show Affiliations

Doddareddy MR
Biochemicals Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
Jung HK
No affiliation info available
Cha JH
No affiliation info available
Cho YS
No affiliation info available
Koh HY
No affiliation info available
Chang MH
No affiliation info available
Pae AN
No affiliation info available

MeSH

Calcium Channel BlockersCalcium Channels, T-TypeDrug DesignModels, ChemicalModels, MolecularMolecular ConformationPredictive Value of TestsQuantitative Structure-Activity RelationshipReproducibility of Results

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15028254

Citation

Doddareddy, Munikumar Reddy, et al. "3D QSAR Studies On T-type Calcium Channel Blockers Using CoMFA and CoMSIA." Bioorganic & Medicinal Chemistry, vol. 12, no. 7, 2004, pp. 1613-21.
Doddareddy MR, Jung HK, Cha JH, et al. 3D QSAR studies on T-type calcium channel blockers using CoMFA and CoMSIA. Bioorg Med Chem. 2004;12(7):1613-21.
Doddareddy, M. R., Jung, H. K., Cha, J. H., Cho, Y. S., Koh, H. Y., Chang, M. H., & Pae, A. N. (2004). 3D QSAR studies on T-type calcium channel blockers using CoMFA and CoMSIA. Bioorganic & Medicinal Chemistry, 12(7), 1613-21.
Doddareddy MR, et al. 3D QSAR Studies On T-type Calcium Channel Blockers Using CoMFA and CoMSIA. Bioorg Med Chem. 2004 Apr 1;12(7):1613-21. PubMed PMID: 15028254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3D QSAR studies on T-type calcium channel blockers using CoMFA and CoMSIA. AU - Doddareddy,Munikumar Reddy, AU - Jung,Hee Kyung, AU - Cha,Joo Hwan, AU - Cho,Yong Seo, AU - Koh,Hun Yeong, AU - Chang,Moon Ho, AU - Pae,Ae Nim, PY - 2004/01/06/received PY - 2004/01/20/revised PY - 2004/01/21/accepted PY - 2004/3/19/pubmed PY - 2004/12/16/medline PY - 2004/3/19/entrez SP - 1613 EP - 21 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 12 IS - 7 N2 - Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of isoxazolyl compounds as a potent T-type calcium channel blockers. A set of 24 structurally similar compounds served to establish the model. Four different conformations of the most active compound were used as template structures for the alignment, three of which were obtained from Catalyst pharmacophore modeling and one by using SYBYL random search option. All CoMFA and CoMSIA models gave cross-validated r(2) (q(2)) value of more than 0.5 and conventional r(2) value of more than 0.85. The predictive ability of the models was validated by an external test set of 10 compounds, which gave satisfactory pred r(2) values ranging from 0.577 to 0.866 for all models. Best predictions were obtained with CoMFA std model of Conformer no: 3 alignment (q(2)=0.756, r(2)=0.963), giving predictive r(2) value of 0.866 for the test set. CoMFA and CoMSIA contour maps were used to analyze the structural features of the ligands accounting for the activity in terms of positively contributing physicochemical properties: steric, electrostatic, hydrophobic and hydrogen bonding fields. SN - 0968-0896 UR - https://www.unboundmedicine.com/medline/citation/15028254/3D_QSAR_studies_on_T_type_calcium_channel_blockers_using_CoMFA_and_CoMSIA_ DB - PRIME DP - Unbound Medicine ER -