2. Academic Validation
  3. 7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase

7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase

  • J Med Chem. 1998 Jun 18;41(13):2268-77. doi: 10.1021/jm9800090.
A J Duplantier 1,  C J Andresen,  J B Cheng,  V L Cohan,  C Decker,  F M DiCapua,  K G Kraus,  K L Johnson,  C R Turner,  J P UmLand,  J W Watson,  R T Wester,  A S Williams,  J A Williams
Affiliations

Affiliation

  • 1 Central Research Division, Pfizer Inc, Groton, Connecticut 06340, USA.
PMID: 9632360 DOI: 10.1021/jm9800090
Abstract

High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 Inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent than 11 with IC50 values of 0.03-1.6 microM. One such compound, CP-220,629 (22) (IC50 = 0.44 microM), was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a significant reduction in eosinophil (55%), neutrophil (65%), and IL-1beta (82%) responses to antigen challenge in atopic monkeys (10 mg/kg, po).

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