A novel Imatinib analog inhibitor of chronic myeloid leukemia: design, synthesis, and characterization. Explanation of its folded conformation

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 show..., 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)., , # 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...