1.
Bioorg Med Chem Lett
; 23(20): 5528-32, 2013 Oct 15.
Article
in English
| MEDLINE
| ID: mdl-24018187
ABSTRACT
The optimization of oxazole-based PDE4 inhibitor 1 has led to the identification of both oral (compound 16) and inhaled (compound 34) PDE4 inhibitors. Selectivity against PDE10/PDE11, off target screening, and in vivo activity in the rat are discussed.
Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 4/chemistry , Oxazoles/chemistry , Proline/analogs & derivatives , Quinolines/chemical synthesis , Administration, Oral , Animals , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Drug Evaluation, Preclinical , Half-Life , Inhalation , Oxazoles/chemical synthesis , Oxazoles/pharmacokinetics , Phosphodiesterase 4 Inhibitors/chemical synthesis , Phosphodiesterase 4 Inhibitors/chemistry , Phosphodiesterase 4 Inhibitors/pharmacokinetics , Proline/chemical synthesis , Proline/chemistry , Proline/pharmacokinetics , Quinolines/chemistry , Quinolines/pharmacokinetics , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 23(11): 3262-6, 2013 Jun 01.
Article
in English
| MEDLINE
| ID: mdl-23602398
ABSTRACT
Conformation restriction of linear N-alkylanilide MK2 inhibitors to their E-conformer was developed. This strategy enabled rapid advance in identifying a series of potent non-ATP competitive inhibitors that exhibited cell based activity in anti-TNFα assay.