Gene/Protein
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Symptom
Drug
Enzyme
Compound
Pivot Concepts:
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Target Concepts:
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Query: UMLS:C0423716 (
Neuropathic pain
)
1,417
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Neuropathic pain
, epilepsy, insomnia, and tremor disorder may arrive from an increase of intracellular Ca
2+
concentration through a dysfunction of T-type Ca
2+
channels. Thus, T-type calcium channels could be a target in drug discovery for the treatments of neuropathic pain and epilepsy. From rational drug design approach, a group of 2,5-disubstituted
1,3,4-oxadiazole
molecules was synthesized and their selective T-type channel inhibitions were evaluated. The synthetic strategy consists of a short sequence of three reactions: (i) condensation of thiosemicarbazide with acid chlorides; (ii) ring closing by 1,3-dibromo-5,5- dimethylhydantoin; and (iii) coupling with various acid chlorides. 5-Chloro-
N
-(5- phenyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxamide (
11
) was found to selectively inhibit T-type Ca
2+
channel over Na
+
and K
+
channels in mouse dorsal root ganglion neurons and/or human embryonic kidney (HEK)-293 cells and to suppress seizure-induced death in mouse model. Consequently, compound
11
is a useful probe for investigation of physiologic and pathophysiologic roles of the T-channel, and provides a basis to develop a novel therapeutic to treat chronic neuropathic and inflammatory pains.
...
PMID:SYNTHESIS OF 1,3,4-OXADIAZOLES AS SELECTIVE T-TYPE CALCIUM CHANNEL INHIBITORS. 3277 46
