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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Homochiral drug design and development by racemization
1Department of Chemistry, Jamia Millia Islamia (Central University), Jamia Nagar, New Delhi 110025, India. drimran_ali@yahoo.com
Combinatorial Chemistry & High Throughput Screening
|September 28, 2007
Summary
Homochiral drugs can racemize in the body, forming inactive or toxic forms. Understanding drug racemization is crucial for safe dosage and effective treatment.
Area of Science:
- Pharmacology
- Drug Development
- Chemical Kinetics
Background:
- Regulatory agencies recommend optically active (homochiral) drugs due to potential inactivity or toxicity of enantiomers.
- Some homochiral drugs undergo racemization in vivo, generating other enantiomers that may be harmful or reduce therapeutic efficacy.
- Racemization decreases the concentration of the active enantiomer, necessitating careful dosage considerations.
Purpose of the Study:
- To review in vitro and in vivo racemization of homochiral drugs.
- To explore factors influencing drug racemization.
- To discuss racemization mechanisms and suggest safe drug dosages.
Main Methods:
- Review of existing literature on homochiral drug racemization.
- Analysis of variables affecting racemization, including temperature, concentration, pH, and excipients like cyclodextrins.
- Discussion of racemization mechanisms.
Main Results:
- Racemization is influenced by various factors such as temperature, drug concentration, pH, and ionic strength.
- The formation of inclusion complexes with agents like cyclodextrins can affect racemization rates.
- Different mechanisms contribute to the racemization of homochiral drugs.
Conclusions:
- Racemization of homochiral drugs is a significant concern in pharmaceutical development and clinical use.
- Understanding the factors and mechanisms governing racemization is essential for determining safe and effective drug dosages.
- Further studies on drug racemization are needed to ensure patient safety and therapeutic outcomes.
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