Discovery of 3-OH-3-methylpipecolic hydroxamates: potent orally active inhibitors of aggrecanase and MMP-13.

@article{Noe2005DiscoveryO3,
  title={Discovery of 3-OH-3-methylpipecolic hydroxamates: potent orally active inhibitors of aggrecanase and MMP-13.},
  author={Mark C. Noe and Vijayalakshmi Natarajan and Sheri L. Snow and Lilli A. Wolf-Gouveia and Peter G. Mitchell and Lori L. Lopresti-Morrow and Lisa Malaine Reeves and Sue A. Yocum and Ivan G. Otterness and Marcia A Bliven and Thomas J. Carty and John T Barberia and F. J. Sweeney and Jennifer L. Liras and Marcie L Vaughn},
  journal={Bioorganic & medicinal chemistry letters},
  year={2005},
  volume={15 14},
  pages={
          3385-8
        }
}
A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1' pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic… CONTINUE READING

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