Assessing the issue of instability due to Michael adduct formation in novel chemical entities possessing a carbon-carbon double bond during early drug development--applicability of common laboratory analytical protocols.

@article{Polepally2008AssessingTI,
  title={Assessing the issue of instability due to Michael adduct formation in novel chemical entities possessing a carbon-carbon double bond during early drug development--applicability of common laboratory analytical protocols.},
  author={Akshanth R. Polepally and V. Kumar and Ravikanth Bhamidipati and J. Kota and S. A. Naveed and K. H. Reddy and R. Mamidi and N. Selvakumar and R. Mullangi and N. Srinivas},
  journal={Biomedical chromatography : BMC},
  year={2008},
  volume={22 9},
  pages={
          960-76
        }
}
The discovery of small-molecule novel chemical entities (NCEs) is often a complex play between appropriate structural requirements and optimization of the desired efficacy, safety and pharmacokinetic properties. One of the typical structural variants such as having an active carbon-carbon double bond (alpha, beta-unsaturated carbonyl group) in xenobiotics may lead to stability issues. Such functionalities are extremely reactive, paving way to nucleophilic attack by endogenously occurring and… Expand
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References

SHOWING 1-4 OF 4 REFERENCES
Verlukast (MK-0679) conjugation with glutathione by rat liver and kidney cytosols and excretion in the bile.
  • 11
Glutathione S-aralkyltransferase.
  • 50
Risks in new drug development: Approval success rates for investigational drugs
  • J. DiMasi
  • Business, Medicine
  • Clinical pharmacology and therapeutics
  • 2001
  • 430
  • PDF