Daprodustat Impurity;3036242-54-0
WhatsAPP: +86 17386083646
E-mail: anna@molcoo.com
Well-defined and distinct structure: Its structure contains a dicyclohexyl-substituted trioxohexahydropyrimidine ring and ethyl ester group, which is significantly different from the pyrazolopyrimidinone structure of Daprodustat. It can be accurately identified by techniques such as HPLC and GC-MS, providing a specific marker for impurity detection;
High stability and traceability: The pyrimidine ring and ester group are stable under neutral conditions. As a by-product of the ureido cyclization reaction in Daprodustat synthesis, it directly reflects the condensation efficiency of cyclohexylurea intermediates, improving the accuracy of process tracing;
High detection sensitivity: The conjugated structure of ester and carbonyl groups has characteristic absorption in the UV region (220-240nm), enabling trace analysis via HPLC-UV, reducing detection costs and enhancing method applicability.
Pharmaceutical quality control: Used as an impurity reference standard to identify and quantify Daprodustat Impurity 18 in Daprodustat APIs, ensuring residual by-products from ureido cyclization meet quality standards;
Synthesis process optimization: Reducing the formation of trioxopyrimidine by-products by monitoring the impurity content and optimizing cyclization catalysts (e.g., organic bases) and reaction temperature to improve main product yield;
Reaction pathway analysis: Assisting in analyzing the competitive reaction pathways of ureido cyclization in Daprodustat synthesis, providing data support for process selection.
Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) used in the treatment of anemia associated with chronic kidney disease. Its synthesis involves cyclization of ureido compounds. Abnormal cyclization of cyclohexylurea intermediates during condensation may generate pyrimidine impurities such as ethyl 1,3-dicyclohexyl-2,4,6-trioxohexahydropyrimidine-5-carboxylate. The presence of such impurities may affect drug purity and stability, making their control a key part of Daprodustat quality assurance.
Current research focuses on:
Detection method optimization: Using UPLC-DAD to optimize mobile phases (acetonitrile-water systems) based on the strong polarity of the pyrimidine ring, achieving trace detection of this impurity (detection limits up to ppm level);
Cyclization process improvement: Developing novel Lewis acid catalysts to enhance regioselectivity of ureido cyclization and reduce the formation of trioxopyrimidine by-products;
Hydrolysis behavior studies: Investigating the conversion of this impurity in subsequent hydrolysis and decarboxylation steps to assess its impact on the purity of Daprodustat final products;
Limit standardization: Establishing rational impurity limits based on multi-batch production data and toxicological evaluations, integrating them into the quality control system for Daprodustat APIs.
We can also customize related analogues and modified peptides including HPLC, MS, 1H-NMR, MS, HPLC, IR, UV, COA, MSDS.
This product is intended for laboratory use only!
WhatsAPP: +86 17386083646
E-mail: anna@molcoo.com
China
