Agents for the treatment of overactive detrusor. I. Synthesis and structure-activity relationships of 1,1'-biphenyl derivatives. |
| |
| Authors: | K Take K Okumura K Takimoto M Kato M Ohtsuka Y Shiokawa |
| |
| Institution: | New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. |
| |
| Abstract: | 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). |
| |
| Keywords: | |
|
|
