Identification of Novel 6-Thioguanine Based Small Molecule ENPP1 Inhibitors: Data on Synthesis, Biological Evaluation and ADME Properties

This raw data files corresponds to the article: “Identification of Novel 6-Thioguanine Based Small Molecule ENPP1 Inhibitors: Data on Synthesis, Biological Evaluation and ADME Properties”. In this data-in-brief article, we have reported the synthetic schemes, data for analytical characterisation, ADME, stability in SGF/SIF/PBS and in vitro biology of the four compounds (1-4; numbers in the original article 23, 34, 42 and 43, respectively) and the corresponding raw data files are uploaded here. Data provided in this article is of high significance for further development of the ENPP1 inhibitors.
NMR data was acquired using Bruker Avance II 400 MHz NMR Spectrometer. Mass data was acquired using Shimadzu LCMS-2020 having single quadruple mass analyser. HPLC data was acquired using 1260 Agilent Infinity II HPLC system. Melting point was taken on Labmatrix Manufacturing LLP. Regression curve fit was taken using GraphPad Prism® software and biology data was accomplished using SpectraMax® iD3 microplate reader. Shimadzu Nexera x2 UPLC system along with AB Sciex 4500 Triple Quad Mass spectrometer was used for analysis of samples from liver microsomal stability, plasma stability and plasma protein binding study. Nephelostar Plus Nephelometer was used for kinetic solubility study. Shimadzu Nexera x2 UPLC system along with AB Sciex 4500 QTrap, AB Sciex 4500 Triple Quad Mass spectrometer was used for analysis of samples from CYP inhibition study. Shimadzu SIL-HTc LC system along with MAPI-4000 (MDS Sciex) mass spectrometer was used for Caco-2 permeability assay. API 3200 Q Trap LC-MS/MS was used for in vitro metabolic stability study in suspension hepatocytes.

本原始数据集配套的学术论文为：《基于新型6-硫鸟嘌呤的小分子ENPP1抑制剂：合成、生物学评价及ADME（吸收、分布、代谢、排泄）特性相关数据》。在本篇数据简报文章中，我们报道了4种化合物（编号1-4，分别对应原文中的23、34、42、43号化合物）的合成路线、分析表征数据、ADME特性、在SGF（模拟胃液）/SIF（模拟肠液）/PBS（磷酸盐缓冲液）中的稳定性以及体外生物学数据，相关原始数据集已随本文上传。本文所提供的数据对于ENPP1抑制剂的后续研发具有重要指导意义。核磁共振（NMR）数据通过布鲁克Avance II 400 MHz核磁共振波谱仪采集。质谱数据通过配备单四极杆质量分析器的岛津LCMS-2020质谱仪采集。高效液相色谱（HPLC）数据通过安捷伦1260 Infinity II高效液相色谱系统采集。熔点数据通过Labmatrix Manufacturing LLP仪器测定。回归曲线拟合采用GraphPad Prism®软件完成，生物学数据通过SpectraMax® iD3微孔板读数仪获取。肝微粒体稳定性、血浆稳定性及血浆蛋白结合研究的样本分析，采用岛津Nexera x2超高效液相色谱（UPLC）系统与AB Sciex 4500三重四极杆质谱仪联用完成。动力学溶解度研究采用Nephelostar Plus浊度仪完成。细胞色素P450（CYP）抑制实验的样本分析，采用岛津Nexera x2 UPLC系统与AB Sciex 4500 QTrap、AB Sciex 4500三重四极杆质谱仪联用完成。Caco-2细胞通透性实验采用岛津SIL-HTc液相色谱系统与MAPI-4000（MDS Sciex）质谱仪完成。悬浮肝细胞的体外代谢稳定性研究采用API 3200 Q Trap液相色谱-串联质谱（LC-MS/MS）系统完成。