New orally active PDE4 inhibitors with therapeutic potential.
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.
Ochiai
Hiroshi
H
Minase Research Institute, Ono Pharmaceutical Co. Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Ishida
Akiharu
A
Ohtani
Tazumi
T
Kusumi
Kensuke
K
Kishikawa
Katuya
K
Obata
Takaaki
T
Nakai
Hisao
H
Toda
Masaaki
M
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
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