66937-58-4Relevant academic research and scientific papers
Practical Synthesis of BILA 2157 BS, a Potent and Orally Active Renin Inhibitor: Use of an Enzyme-Catalyzed Hydrolysis for the Preparation of Homochiral Succinic Acid Derivatives
Beaulieu, Pierre L.,Gillard, James,Bailey, Murray,Beaulieu, Christian,Duceppe, Jean-Simon,Lavallee, Pierre,Wernic, Dominik
, p. 6622 - 6634 (1999)
We have developed a highly convergent and stereoselective synthesis of BILA 2157 BS, a potent and orally active renin inhibitor. The synthesis proceeds in 15 distinct chemical steps (with several integrated, multistep operations) from aminodiol 4. The key step in the synthesis involves the use of an enantiospecific, enzyme-catalyzed hydrolysis of a substituted succinate diester to provide a homochiral succinic acid derivative in 98% enantiomeric excess (≥2.5 kg scale). Recycling of the unwanted enantiomer is accomplished through base-catalyzed racemization, leading to an efficient deracemization of the starting racemic diester. The entire sequence proceeds without chromatographic purifications and delivers the product with >97% homogeneity. In addition, compared to the previously reported syntheses of BILA 2157 BS, this approach avoids the use of expensive chiral auxiliaries and cryogenics and, thus, should be amenable to the preparation of large quantities of this peptidomimetic inhibitor.
Seeing Elastin: A Near-Infrared Zwitterionic Fluorescent Probe for In Vivo Elastin Imaging
Su, Dongdong,Teoh, Chai Lean,Park, Sung-Jin,Kim, Jong-Jin,Samanta, Animesh,Bi, Renzhe,Dinish,Olivo, Malini,Piantino, Marie,Louis, Fiona,Matsusaki, Michiya,Kim, Seong Soon,Bae, Myung Ae,Chang, Young-Tae
supporting information, p. 1128 - 1138 (2018/05/22)
Elastic fibers are present in a variety of tissues and are responsible for their resilience. Until now, no optical contrast agent in the near-infrared (NIR) wavelength range of 700–900 nm has been reported for the imaging of elastic fibers. Here, we report the discovery of a NIR zwitterionic elastin probe ElaNIR (elastin NIR) through fluorescent-image-based screening. The probe was successfully applied for in vitro, ex vivo, and in vivo imaging by various imaging modalities. Age-related elastin differences shown by in vivo fluorescent and photoacoustic imaging indicated that ElaNIR can be a potentially convenient tool for uncovering changes of elastin in live models. Technological advancement of microscopic imaging has spurred the development of molecular probes for the detection of biologically and environmentally important analytes. Among fluorescent imaging tools, near-infrared (NIR) fluorescent molecules have been popular for in vivo imaging because of their ability to penetrate tissue deeper with reduced scattering and autofluorescence. Here, we report the discovery of the NIR zwitterionic elastin probe ElaNIR. We found that ElaNIR showed selective binding for elastin, such as those in the aorta, lungs, and skin. ElaNIR also allowed visualization and quantification of elastin levels in young and old mice, which reflect age-dependent changes of elastin in vivo. This makes ElaNIR a unique chemical tool for monitoring changes of elastin in tissue or animal models and provides new opportunities to study the effects of chemical compounds on elastin levels in biological processes. The near-infrared zwitterionic elastin probe ElaNIR for in vivo imaging of elastin structures was found through fluorescent-image-based screening. ElaNIR is well suited for in vitro, ex vivo, and in vivo imaging of elastin and also allows visualization and quantification of elastin levels in young and old mice, which reflect age-dependent changes of elastin in vivo.
CALCIUM ION CHANNEL MODULATORS and USES THEREOF
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Page/Page column 73, (2010/04/27)
Compounds of formula (I), wherein R1 is hydrogen, hydroxyl or aralkyl; R2 is an optionally substituted alkyl, aryl or heteroaryl (said substituents are selected from hydroxyl, alkoxyl, haloalkoxyl, aryl, heteroaryl, cycloalkyl, amino, monoalkylamino, dialkylamino, alkylsulphonyl, alkylsulphinyl, alkylsulphonylamino, acylamino, saturated or partially unsaturated heterocyclic groups and groups of formula COY); W is selected from oxygen, sulphur, groups of formula NR7, wherein R7 is hydrogen, alkyl, aryl or heteroaryl and groups of formula CR8R9, wherein R8 and R9 are hydrogen, alkyl, aryl or heteroaryl; and X is selected from nitrogen and groups of formula CR10, wherein R10 is hydrogen, alkyl, aryl, heteroaryl, halogen or haloalkyl, inhibit the interaction between Cavx channels and Cavβ proteins and are of use in the treatment and prevention of a number of diseases and conditions including pain and lower urinary tract disorders.
INDOLE- 3 -GLYOXYLAMIDE DERIVATIVES FOR USE AS CALCIUM ION CHANNEL MODULATORS
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Page/Page column 48, (2009/12/05)
Compounds of formula (I) are of use in treating a range of conditions, including pain.
