Agents for the treatment of overactive detrusor. I. Synthesis and structure-activity relationships of 1,1'-biphenyl derivatives.
A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters were synthesized and examined for their inhibitory activity on guinea-pig detrusor muscle contraction at electrical field stimulation in vitro. Among them, 6-isopropyl 2-methyl 3-hydroxy-5-methyl-2'-nitro-(1,1'-biphenyl)-2,6-dicarboxylate, FR75513 (8a) was one of the potent compounds (IC50 = 3.3 x 10(-6) g/ml). This compound (8a) exhibited a strong inhibitory activity on detrusor contraction after intravenous administration in anesthetized rats (ID50 = 0.04 mg/kg).
Take
K
K
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Okumura
K
K
Takimoto
K
K
Kato
M
M
Ohtsuka
M
M
Shiokawa
Y
Y
D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects; D014555:Urination Disorders / Q000188:drug therapy*
D001713:Biphenyl Compounds; C073508:FR 75513