The design of a novel series of muscarinic receptor antagonists leading to AZD8683, a potential inhaled treatment for COPD.

@article{Mete2013TheDO,
  title={The design of a novel series of muscarinic receptor antagonists leading to AZD8683, a potential inhaled treatment for COPD.},
  author={A. Mete and K. Bowers and R. Bull and H. Coope and D. Donald and K. J. Escott and R. Ford and K. Grime and A. Mather and Nicholas C Ray and V. Russell},
  journal={Bioorganic & medicinal chemistry letters},
  year={2013},
  volume={23 23},
  pages={
          6248-53
        }
}
A novel series of muscarinic receptor antagonists was developed, with the aim of identifying a compound with high M3 receptor potency and a reduced risk of dose-limiting side effects with potential for the treatment of COPD. Initial compound modifications led to a novel cycloheptyl series, which was improved by focusing on a quinuclidine sub-series. A wide range of N-substituents was evaluated to determine the optimal substituent providing a high M3 receptor potency, high intrinsic clearance… Expand
8 Citations

Figures, Tables, and Topics from this paper

Long-Acting Muscarinic Antagonists Under Investigational to Treat Chronic Obstructive Pulmonary Disease
  • Highly Influenced
  • PDF
PKPD modelling of PR and QRS intervals in conscious dogs using standard safety pharmacology data.
  • 6
Emerging therapeutic strategies in COPD.
  • 18
Predicting QRS and PR interval prolongations in humans using nonclinical data
  • 4
  • PDF

References

SHOWING 1-10 OF 12 REFERENCES
Long-acting muscarinic antagonists for the treatment of chronic obstructive pulmonary disease
  • D. Laine
  • Medicine
  • Expert review of clinical pharmacology
  • 2010
  • 10
Muscarinic receptor subtype pharmacology and physiology.
  • R. Eglen
  • Biology, Medicine
  • Progress in medicinal chemistry
  • 2005
  • 176
Medicinal chemistry and therapeutic potential of muscarinic M3 antagonists
  • 33
Potential for long-acting muscarinic antagonists in chronic obstructive pulmonary disease
  • G. Joos
  • Medicine
  • Expert opinion on investigational drugs
  • 2010
  • 20
Characterization of Aclidinium Bromide, a Novel Inhaled Muscarinic Antagonist, with Long Duration of Action and a Favorable Pharmacological Profile
  • 118
  • PDF
The discovery of AZD9164, a novel muscarinic M3 antagonist.
  • 15
Novel long‐acting bronchodilators for COPD and asthma
  • 132
...
1
2
...