Discovery of FR166124, a novel water-soluble pyrazolo-[1,5-a]pyridine adenosine A1 receptor antagonist.
Novel 3-(2-cycloalkyl and cycloalkenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazo lo [1,5-a]-pyridines were synthesized and evaluated for their adenosine A1 receptor binding activities. In this series, FR166124 (3) was found to be the most potent and selective adenosine A1 receptor antagonist, and the double bond of the cyclohexenyl acetic acid group was essential for selectivity of A1 receptor binding. Furthermore, the solubility in water of the sodium salt of FR 166124 was high.
Kuroda
S
S
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Akahane
A
A
Itani
H
H
Nishimura
S
S
Durkin
K
K
Kinoshita
T
T
Tenda
Y
Y
Sakane
K
K
D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry; D014970:Xanthines / Q000737:chemistry / Q000494:pharmacology
D000959:Antihypertensive Agents; C121286:FR 166124; D010880:Piperidines; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles; D011725:Pyridines; D018047:Receptors, Purinergic P1; D014970:Xanthines; D014867:Water; C102861:FK 838; C032727:piperidine; C051360:1,3-dipropyl-8-cyclopentylxanthine