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Ligand-based molecular design of 4-benzylpiperidinealkylureas and amides as CCR3 antagonists

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Abstract

Asthma is an inflammatory disease of the lungs. Clinical studies suggest that eotaxin and chemokine receptor-3 (CCR3) play a primary role in the recruitment of eosinophils in allergic asthma. Development of novel and potent CCR3 antagonists could provide a novel mechanism for inhibition of this recruitment process, thereby preventing asthma. With the intention of designing new ligands with enhanced inhibitor potencies against CCR3, a 3D-QSAR CoMFA study was carried out on 41 4-benzylpiperidinealkylureas and amide derivatives. The best statistics of the developed CoMFA model were r 2 = 0.960, \( r_{cv}^2 = 0.589 \), n = 32 for the training set and \( r_{pred}^2 = 0.619 \), n = 9 for the test set. The generated 3D-QSAR contribution maps shed some light on the effects of the substitution pattern related to CCR3 antagonist activity.

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Acknowledgements

The authors are thankful to the Department of Pharmaceuticals, Govt. of India, for financial support. V.J. and A.P. gratefully acknowledge financial support received from the department in the form of a Junior Research Fellowship. S.G. is the recipient of a Senior Research Fellowship from the Council of Scientific and Industrial Research (New Delhi).

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Authors and Affiliations

  1. Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160 062, Punjab, India

    Vaibhav Jain, Ashish Pandey, Shikhar Gupta & C. Gopi Mohan

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  1. Vaibhav Jain
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  2. Ashish Pandey
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  3. Shikhar Gupta
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  4. C. Gopi Mohan
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Correspondence to C. Gopi Mohan.

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Jain, V., Pandey, A., Gupta, S. et al. Ligand-based molecular design of 4-benzylpiperidinealkylureas and amides as CCR3 antagonists. J Mol Model 16, 669–676 (2010). https://doi.org/10.1007/s00894-009-0621-z

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  • DOI: https://doi.org/10.1007/s00894-009-0621-z

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