ns-004 and Stroke
ns-004 has been researched along with Stroke* in 2 studies
Other Studies
2 other study(ies) available for ns-004 and Stroke
| Article | Year |
|---|---|
3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011: opener of large-conductance Ca(2+)-activated potassium (maxi-K) channels, identification, solubility, and SAR.
Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles. Topics: Animals; Brain; Crystallography, X-Ray; Female; In Vitro Techniques; Ion Channel Gating; Large-Conductance Calcium-Activated Potassium Channels; Molecular Structure; Oocytes; Oxadiazoles; Patch-Clamp Techniques; Plasma; Rats; Rats, Inbred SHR; Solubility; Stroke; Structure-Activity Relationship; Xenopus laevis | 2007 |
The synthesis and structure-activity relationships of 4-aryl-3-aminoquinolin-2-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel openers targeted for post-stroke neuroprotection.
A series of 4-aryl-3-aminoquinoline-2-one derivatives was synthesized and evaluated as activators of the cloned maxi-K channel mSlo (hSlo) expressed in Xenopus laevis oocytes using electrophysiological methods. A brain penetrable activator of maxi-K channels was identified and shown to be significantly active in the MCAO model of stroke. Topics: Animals; Brain; Clone Cells; Disease Models, Animal; Electrophysiology; Large-Conductance Calcium-Activated Potassium Channels; Male; Membrane Potentials; Neuroprotective Agents; Oocytes; Patch-Clamp Techniques; Potassium Channels, Calcium-Activated; Quinolones; Rats; Stroke; Structure-Activity Relationship; Xenopus laevis | 2002 |