Lead compound

Lead compound is a kind of compound with pharmacological or biological activity, but it may have some unsuitable properties, such as high toxicity, low bioavailability or poor metabolic stability, etc. Further optimization of the structure and improvement of various properties are needed to meet the criteria of clinical drug candidate.

Based on the structure-activity and structure-relationship analysis of the lead compound, MedChemExpress (MCE) adopts traditional pharmacochemical methods and modern methods to modify or modify the structure of the lead compound to reduce the defects of the lead compound (not high enough activity, unstable chemical structure, high toxicity, poor selectivity, unreasonable pharmacokinetic properties, etc.). Specific optimization methods include but are not limited to: rational drug design based on 3D quantitative structure-activity relationship and CADD, classical and non-classical group replacement based on bioelectron isostery, computational skeleton transition, local structural modification and conformation restriction based on eutectic structure, molecular hybridization based on target, etc.

Successful Case
Optimal design of small molecule inhibitor for a protein

• 1. Structure-Activity Relationship Analysis
  By studying the relationship between structure and activity, the key structural elements and active groups were found.
• 2. Drug Design and Synthesis Based on CADD
  Based on structure-activity relationship analysis, make full use of CADD technology, participate in the design of a number of patented new molecules, and quickly synthesize multiple types of molecules within two months. The compounds have been tested for activity, and the best lead molecules have the same activity as the patented compounds.
• 3. Optimization of Pharmacokinetic Properties
  Based on in vivo test data, the oral exposure of highly active lead compounds was optimized, and the rapid and efficient synthesis test iteration was performed within a few months. After multiple rounds of optimization, hundreds of molecules were synthesized, and the optimization of the preferred molecular process was completed.
• 4. Cardiotoxicity Assessment of Preferred Compounds
• 5. The optimal compounds were selected as clinical candidate compounds based on the overall performance of in vivo efficacy and ADME/PK.

Service Process