DOI: 10.5061/dryad.8931zcs1b
title: Data from: A novel Imatinib analog inhibitor of chronic myeloid leukemia: design, synthesis, and characterization. Explanation of its folded conformation

description: Chronic Myeloid Leukemia (CML) is primarily treated using Imatinib
 mesylate, a tyrosine kinase inhibitor (TKI) targeting the Bcr-Abl
 oncoprotein. However, the development of drug resistance and adverse side
 effects necessitates the exploration of alternative therapeutic agents.
 This study presents the synthesis and characterization of a novel Imatinib
 analog,
 3-chloro-N-(2-methyl-5-((4-(pyridin-2-yl)pyrimidin-2-yl)amino)phenyl)benzamide (PAPP1). The compound’s structure was elucidated using X-ray crystallography and spectroscopic techniques, including NMR, IR, and UV/Vis. Crystallographic analysis reveals that PAPP1 consists of a phenyl-amino-pyridine-pyrimidine (PAPP) scaffold with substituted aromatic rings forming a nearly coplanar geometry. Additionally, supramolecular interactions in the crystal are mediated by hydrogen bonds and dispersion forces, forming dimers and layered structures. Molecular docking studies demonstrate strong binding affinity to the Abl enzyme, with PAPP1 showing comparable binding energy to Imatinib, indicating its potential as a lead compound for further development. Computational studies, including molecular electrostatic potential and vibrational analysis, provide further support for the structural stability and bioactivity of PAPP1. These findings suggest that PAPP could be a promising scaffold for future CML drug design, offering a potential alternative to existing TKIs, and PAPP1 is a promising lead susceptible to optimization.
description: Diffraction data for the PAPP1 compound was collected using a
 Bruker AXS Enraf-Nonius KappaCCD Diffractometer with Cu Kα radiation (λ =
 1.5418 Å). The data was corrected and solved using direct methods with
 SHELXS-97 (Sheldrick,
 2008) and refined by full-matrix least-squares methods on F²
 with SHELXL-2014 (Sheldrick,
 2015). All hydrogen atoms, except H–N and Hw–O, were placed in
 geometrically idealized positions: C—H = 0.95 Å and C—H (methyl) = 0.98 Å.
 These hydrogen atoms were refined using a riding model approximation with
 U_iso(H) = 1.2 U_eq (for ring atoms) and U_iso(H) = 1.5 U_eq (for methyl
 atoms). The H–N and Hw–O atoms were located from Fourier difference maps,
 and their coordinates were refined freely. The accuracy of the model was
 confirmed by low residuals in the final difference map, with peak and hole
 values of 0.290 e·Å⁻³ and -0.314 e·Å⁻³, respectively. Mercury software
 generated Molecular and supramolecular graphics (Macrae et al.,
 2020).
description: # A novel Imatinib analog inhibitor of chronic myeloid leukemia: design,
 synthesis, and characterization. Explanation of its folded conformation
 [https://doi.org/10.5061/dryad.8931zcs1b](https://doi.org/10.5061/dryad.8931zcs1b) ## Description of the data and file structure We are providing the following data to facilitate the validation of our crystallographic findings for the main molecule, PAPP1, and the computational results derived from these crystallographic data. ### Files and variables #### File: final\_files\_220924\_rsos.tar **Description:**  * .cif file: Contains essential crystallographic information, including atomic coordinates, unit cell parameters, model data, and data refinement details. - .hkl file: Provides raw reflection data from X-ray diffraction experiments, including reflection intensities and coordinates. - .res file: Includes structure refinement information, such as atomic displacement parameters (ADPs), thermal displacement factors, and any constraints applied during refinement. In addition, we have included a supporting information PDF, which details the crystal data and structure refinement, bond lengths, and angles for PAPP1. This PDF also contains spectroscopic data in image format, representing the processed spectra of all isolated intermediates from the synthesis process of the main molecule, replicated and discussed in the main text. ## Code/software **Recommended software:** The following software programs are compatible with the supporting information provided. Additionally, CrystalExplorer allows for advanced calculations, such as Hirshfeld Surface analysis and Energetic Frameworks: * Mercury * Olex2 * CrystalExplorer