Novel cerebroprotective agents with central nervous system stimulating activity. 1. Synthesis and pharmacology of 1-amino-7-hydroxyindan derivatives.
To develop a novel cerebroprotective agent with central nervous system (CNS) stimulating activity, a series of 1-amino-7-hydroxyindan derivatives was synthesized, and their effects on the survival time of mice under hypoxic conditions were tested. CNS-stimulating activity was also evaluated by examining the promotional effect on the recovery from cerebral concussion induced coma in mice. Several compounds prolonged the survival time of mice in hypoxic conditions at a dose of 30 mg/kg (sc or ip) and 100 mg/kg (po). They also exhibited the promotional effects on recovery from coma at a dose of 100 mg/kg po. The three most potent compounds in both tests, 1-amino-7-hydroxy-6-(1-methylpropyl)indan, 1-amino-7-hydroxy-4, 6-dimethyl-2-phenylindan, and 1-amino-7-hydroxy-2,2,4,6-tetramethylindan were selected for further investigations. Structure-activity relationships were also discussed.
Otsuka Pharmaceutical Company, Ltd. Third Institute of New Drug Research, Tokushima.
Y
Y
Oshiro
Y
Y
Sakurai
T
T
Tanaka
H
H
Ueda
T
T
Kikuchi
K
K
Tottori
D000818:Animals; D000697:Central Nervous System Stimulants / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D003128:Coma / Q000188:drug therapy; D003461:Crystallography; D000860:Hypoxia / Q000188:drug therapy; D007189:Indans / Q000138:chemical synthesis* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013329:Structure-Activity Relationship
D000697:Central Nervous System Stimulants; D007189:Indans