202822-68-2Relevant academic research and scientific papers
A BMS - 191011 synthetic method
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, (2017/08/23)
The invention relates to a synthetic method for a compound BMS-191011. The method comprises the following steps: taking 4-trifluoromethyl benzoyl hydrazine as a raw material and performing steps of oxidative carbonylation, methyl protection, halogenation, amination, deprotection and the like to prepare BMS-191011. The synthetic method adopts a CO balloon for replacing phosgene, so that the reaction toxicity is reduced and the reaction operability is improved. The method has the characteristics of simple and easily available raw materials, mild reaction conditions and simple operation process.
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
Romine, Jeffrey L.,Martin, Scott W.,Meanwell, Nicholas A.,Gribkoff, Valentin K.,Boissard, Christopher G.,Dworetzky, Steven I.,Natale, Joanne,Moon, Sandra,Ortiz, Astrid,Yeleswaram, Swamy,Pajor, Lorraine,Gao, Qi,Starrett Jr., John E.
, p. 528 - 542 (2007/10/03)
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.
PHOSPHATE DERIVATIVES OF DIARYL 1,3,4-OXADIAZOLONE
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, (2008/06/13)
The present invention provides novel phosphate derivatives having the general formula wherein A, R1 and R2 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are resp
Carbamate derivatives of diaryl 1,3,4-oxadiazolone
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, (2008/06/13)
The present invention provides novel carbamate oxadiazolone derivatives having the general formula wherein R1and R2are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatme
Derivatives of 1,3,4-oxadiazolone
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, (2008/06/13)
The present invention provides novel oxadiazolone derivatives having the general formula wherein A, B, D and R are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are
Carbamate derivatives of diaryl 1,3,4-oxadiazolone
-
, (2008/06/13)
The present invention provides novel carbamate oxadiazolone derivatives having the general formula wherein R1 and R2 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders whic
PHOSPHATE DERIVATIVES OF DIARYL 1,3,4-OXADIAZOLONE
-
, (2008/06/13)
The present invention provides novel phosphate derivatives having the general formula wherein A, R 1 and R 2 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are re
AMINO ACID DERIVATIVES OF DIARYL 1,3,4-OXADIAZOLONE
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, (2008/06/13)
The present invention provides novel amino acid derivatives having the general formula STR1 wherein R 1, R 2 and R 3 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders whic
