title: New orally active PDE4 inhibitors with therapeutic potential.
abstract: Structural optimization of pyrazolopyridine derivative 2, which is one of the newly discovered chemical leads for PDE4 inhibitors from our in-house library, was carried out successfully. The process of discovery of new orally active PDE4 inhibitors, which are expected to possess therapeutic potential, is presented and their structure-activity relationships are discussed.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co. Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ochiai
authors.forename: Akiharu
authors.initials: A
authors.lastname: Ishida
authors.forename: Tazumi
authors.initials: T
authors.lastname: Ohtani
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kusumi
authors.forename: Katuya
authors.initials: K
authors.lastname: Kishikawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Obata
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005289:Ferrets; D005746:Gastric Emptying / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014839:Vomiting / Q000139:chemically induced
chemical_list: D016085:Bronchoconstrictor Agents; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C118531:pyrazolopyridine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4