Product Number: U003012
English Name: Upadacitinib Impurity 12
English Alias: (3R,4S)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
CAS Number: 1310726-59-0
Molecular Formula: C₁₇H₁₉F₃N₆O
Molecular Weight: 380.37
As a stereoisomeric impurity of Upadacitinib, its research value lies in:
Evaluating the effectiveness of stereoselective control in drug synthesis to optimize processes and reduce epimer formation;
Serving as a reference standard for chiral impurity analysis to ensure the content of this isomer in drugs meets strict quality standards;
Assisting in studying the effects of stereoisomers on drug activity, metabolism, and toxicity to provide a basis for safety evaluation.
Drug Development: Used as a chiral impurity reference standard to identify and quantify the (3R,4S) isomer in drugs, evaluating stereochemical purity;
Quality Control: Acting as a standard substance to validate the accuracy of chiral chromatographic analysis methods, ensuring effective control of isomeric impurities during production;
Toxicological Research: Clarifying the potential impact of this impurity on the overall safety of the drug by comparing the biological effects of different stereoisomers.
Upadacitinib, a highly selective JAK1 inhibitor, contains a chiral center in its molecular structure, and different configurations of stereoisomers may be generated during synthesis. Upadacitinib Impurity 12, as the (3R,4S)-configured impurity, forms an epimer with the (3R,4R)-configured parent drug. Since chiral isomers may have different pharmacological activities or toxicities, the study of this impurity is a key link in drug quality control and safety evaluation.
Current research focuses on:
Chiral Synthesis Methods: Developing highly stereoselective impurity preparation processes to obtain high-purity (3R,4S) isomers for research;
Chiral Separation Technologies: Establishing highly sensitive isomer analysis methods using high-performance chiral chromatography (such as HPLC, SFC) or mass spectrometry combined techniques;
Stereoisomeric Effects: Investigating the effects of this impurity on JAK1 inhibitory activity and pharmacokinetics through in vitro activity experiments and animal models;
Process Control Strategies: Analyzing the formation mechanism of this impurity in the synthesis route and optimizing reaction conditions to reduce its generation, ensuring that the limit of chiral impurities in drugs meets the requirements of ICH guidelines.
China
