bms-191011 has been researched along with Stroke* in 2 studies
2 other study(ies) available for bms-191011 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 |
Synthesis of water-soluble prodrugs of BMS-191011: a maxi-K channel opener targeted for post-stroke neuroprotection.
A variety of water-soluble prodrugs of BMS-191011 was synthesized and evaluated for solution state stability and rate of conversion to BMS-191011 in rat and human plasma. The deoxycarnitine ester prodrug (11c) was selected for clinical evaluation based on its superior chemical stability, crystallinity and cleavage to BMS-191011 in human plasma. Topics: Animals; Betaine; Blood; Carnitine; Crystallization; Dose-Response Relationship, Drug; Drug Stability; Heterocyclic Compounds, 3-Ring; Humans; Neuroprotective Agents; Oxadiazoles; Potassium Channels; Prodrugs; Rats; Solubility; Stroke; Structure-Activity Relationship; Water | 2003 |