4-Phenyl-4H-pyrans as IK(Ca) channel blockers.
4-Phenyl-4H-pyrans have been identified as potent and specific IK(Ca) channel blockers. Their synthesis and structure-activity relationships are described. A selected derivative, rac-11, reduces the infarct volume in a rat subdural hematoma model of traumatic brain injury after iv administration.
Urbahns
Klaus
K
Institute of Medicinal Chemistry, Pharma Research Center, Bayer AG, D-42096, Wuppertal, Germany. klaus.urbahns.ku1@bayer.co.jp
Horváth
Ervin
E
Stasch
Johannes Peter
JP
Mauler
Frank
F
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy; D001930:Brain Injuries / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate; D006408:Hematoma, Subdural / Q000188:drug therapy / Q000473:pathology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011714:Pyrans / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013997:Time Factors
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C491575:Kcnn4 protein, rat; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011714:Pyrans; D009543:Nifedipine