title: Synthesis and evaluation of 6-pyrazoylamido-3N-substituted azabicyclo[3,1,0]hexane derivatives as T-type calcium channel inhibitors for treatment of neuropathic pain.
abstract: A new series of aryls, including benzo[d]imidazole/isoxazole/pyrazole, conjugated to 3N-substituted-azabicyclo[3.1.0]hexane derivatives were designed and synthesized as inhibitors of T-type calcium channels. Among the synthesized compounds, 3N-R-substituted azabicyclo[3.1.0]hexane carboxamide derivatives containing 5-isobutyl-1-phenyl-pyrazole ring exhibited potent and selective T-channel inhibition and good metabolic stability without CYP450 inhibition. Compounds 10d and 10e contained hydrophobic substituents at the 3N-position and exhibited potent in vitro efficacy, as well as neuropathic pain alleviation in rats.
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors: Jung Hyun
authors: JH
authors: Kim
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul 136-791, Republic of Korea; School of Science, University of Science and Technology, Daejeon 305-333, Republic of Korea. Electronic address: gsnam@kist.re.kr.
authors: Ghilsoo
authors: G
authors: Nam
mesh_terms: D000284:Administration, Oral; D000818:Animals; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D053961:Azabicyclo Compounds; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D011720:Pyrazoles
keywords: 6-Pyrazoylamido-3-N-substituted-azabicyclo[3.1.0]hexane; Neuropathic pain; T-type calcium channel inhibitor