IKCa-channel blockers. Part 2: discovery of cyclohexadienes.
Novel cyclohexadienes have been identified as potent and specific IK(Ca)-channel blockers. In this communication we describe their synthesis as well as their chemical and biological properties. A selected derivative is being enriched in rat brain and reduces the infarct volume, intracranial pressure as well as the water content in a rat subdural hematoma model of traumatic brain injury after iv administration.
Urbahns
Klaus
K
Institute of Medicinal Chemistry, Pharma Research Center, Bayer Health Care, D-42096 Wuppertal, FRG. klaus.urbahns@astrazeneca.com
Goldmann
Siegfried
S
Krüger
Jochen
J
Horváth
Ervin
E
Schuhmacher
Joachim
J
Grosser
Rolf
R
Hinz
Volker
V
Mauler
Frank
F
D000818:Animals; D001834:Body Water / Q000187:drug effects* / Q000378:metabolism; D020520:Brain Infarction / Q000188:drug therapy; D001930:Brain Injuries / Q000188:drug therapy; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000494:pharmacology*; D053138:Cyclohexenes; D004195:Disease Models, Animal; D006408:Hematoma, Subdural / Q000188:drug therapy; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D007427:Intracranial Pressure / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship
D003510:Cyclohexanes; D053138:Cyclohexenes; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C491575:Kcnn4 protein, rat; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C048401:1,4-cyclohexadiene