2. Academic Validation
  3. Aminopyridinecarboxamide-based inhaled IKK-2 inhibitors for asthma and COPD: Structure-activity relationship

Aminopyridinecarboxamide-based inhaled IKK-2 inhibitors for asthma and COPD: Structure-activity relationship

  • Bioorg Med Chem. 2011 Feb 1;19(3):1242-55. doi: 10.1016/j.bmc.2010.12.027.
Jin Xie 1,  Gennadiy I Poda,  Yiding Hu,  Natalie X Chen,  Richard F Heier,  Serge G Wolfson,  Matthew T Reding,  Patrick J Lennon,  Ravi G Kurumbail,  Shaun R Selness,  Xiong Li,  Nandini N Kishore,  Cynthia D Sommers,  Lori Christine,  Sheri L Bonar,  Neetu Venkatraman,  Sumathy Mathialagan,  Sarah J Brustkern,  Horng-Chih Huang
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Pfizer Inc., 700 Chesterfield Parkway West, St. Louis, MO 63017, USA. [email protected]
PMID: 21236687 DOI: 10.1016/j.bmc.2010.12.027
Abstract

Installation of sites for metabolism in the lead compound PHA-767408 was the key focus of the IKK-2 inhaled program. This paper reports our efforts to identify a novel series of aminopyridinecarboxamide-based IKK-2 inhibitors, which display low nanomolar potency against IKK-2 with long duration of action (DOA), and metabolically labile to phase I and/or phase II metabolizing Enzymes with potential capability for multiple routes of clearance. Several compounds have demonstrated their potential usefulness in the treatment of asthma and chronic obstructive pulmonary disease (COPD).

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