Highly potent PDE4 inhibitors with therapeutic potential.
Based on the hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system (CNS), design and synthesis of a hydrophilic analogue is considered to be one approach to improving the side-effect profile of Ariflo 1. Water-soluble piperidine derivatives were found to possess therapeutic potential.
Ochiai
Hiroshi
H
Minase Research Institute, Ono Pharmaceutical Co. Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Ohtani
Tazumi
T
Ishida
Akiharu
A
Kusumi
Kensuke
K
Kato
Masashi
M
Kohno
Hiroshi
H
Kishikawa
Katuya
K
Obata
Takaaki
T
Nakai
Hisao
H
Toda
Masaaki
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003509:Cyclohexanecarboxylic Acids / Q000009:adverse effects / Q000737:chemistry; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D009570:Nitriles; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020298:U937 Cells
D003509:Cyclohexanecarboxylic Acids; D009570:Nitriles; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D014409:Tumor Necrosis Factor-alpha; C433247:Cilomilast; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4