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Int. J. Mol. Sci. 2013, 14(6), 12037-12053; doi:10.3390/ijms140612037
Article

Three Dimensional Quantitative Structure-Activity Relationship of 5H-Pyrido[4,3-b]indol-4-carboxamide JAK2 Inhibitors

* ,
 and
*
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
* Authors to whom correspondence should be addressed.
Received: 7 April 2013 / Revised: 30 May 2013 / Accepted: 30 May 2013 / Published: 5 June 2013

Abstract

Janus kinase 2 (JAK2) is an intracellular nonreceptor tyrosine kinase that belongs to the JAK family of kinases, which play an important role in survival, proliferation, and differentiation of a variety of cells. JAK2 inhibitors are potential drugs for the treatment of myeloproliferative neoplasms. The three dimensional quantitative structure-activity relationships have been studied on a series of JAK2 inhibitors by comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). The CoMFA model had a cross-validated coefficient q2 of 0.633, and the relation non-cross-validated coefficient r2 of 0.976. The F value is 225.030. The contributions of steric and electrostatic fields to the activity are 55.2% and 44.8%, respectively. For the CoMSIA study, the q2, r2, and F values of the model are 0.614, 0.929, and 88.771, respectively. The contributions of steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond donor fields to the activity are 27.3%, 23.9%, 16.4%, 21.7%, and 10.7%, respectively. The CoMFA and CoMSIA models showed strong predictive ability, and the 3D contour plots give the basis on the structure modification of JAK2 inhibitors.
Keywords: 3D-QSAR; CoMFA; CoMSIA; JAK2 inhibitor; 5H-pyrido[4,3-b]indol-4-carboxamide 3D-QSAR; CoMFA; CoMSIA; JAK2 inhibitor; 5H-pyrido[4,3-b]indol-4-carboxamide
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Wu, X.; Wan, S.; Zhang, J. Three Dimensional Quantitative Structure-Activity Relationship of 5H-Pyrido[4,3-b]indol-4-carboxamide JAK2 Inhibitors. Int. J. Mol. Sci. 2013, 14, 12037-12053.

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