1,720,990 research outputs found
Use of arylalkanolamines as sigma-1 receptor antagonists
No full textThe present invention relates to the novel use of arylalkanolamine compounds with sigma-1 receptor antagonist activity. In particular, the said arylalkanolamine compounds are useful in the treatment of conditions such as, for example, the abuse of psychotropic substances such as cocaine or amphetamines, pain and cancer
Towards sigma1 receptor agonists as neuroprotective agents. Chemical and pharmacological studies of RC-33 enantiomers
No full textSigma1 Receptor Agonists in motor dysfunction pathologies treatment – a medicinal chemistry perspective
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Development of easy-to-use reverse-phase liquid chromatographic methods for determining PRE-084, RC-33 and RC-34 in biological matrices. The first step for in vivo analysis of sigma1 receptor agonists.
No full textOver the years there has been a growing interest in the therapeutic potential for central nervous system pathologies of sigma receptor modulators. The widely studied PRE-084 and our compounds RC-33 and RC-34 are very potent and selective sigma 1 receptor agonists that could represent promising drug candidates for Amyotrophic Lateral Sclerosis (ALS). Herein, we develop and validate robust and easy-to-use reverse-phase chromatographic methods suitable for detecting and quantifying PRE-084, RC-33 and RC-34 in mouse blood, brain and spinal cord. An HPLC/UV/ESI-MS system was employed for analyzing PRE-084 and an HPLC/UV-PDA system for determining RC-33 and RC-34. Chromatographic separations were achieved on Waters Symmetry RP18 column (150× 3.9mm, 5 μm), eluting with water and acetonitrile (both containing 0.1% formic acid) in gradient conditions.
The recovery of PRE-084, RC-33 and RC-34 was >95% in all the considered matrices. Their limits of quantitation and detection were also determined. Validation proved the methods be suitable for separating tested compounds from endogenous interferences, being characterized by good sensitivity, linearity, precision and accuracy. A preliminary central nervous system distribution study showed a high distribution of RC-33 in brain and spinal cord, with concentration values well above the determined limit of quantitation. The proposed methods will be used in future preclinical investigations
Chemical, pharmacological and in vivo pharmacokinetic studies on enantiomerically pure RC-33 compounds, promising neuroprotective agents acting as sigma1 receptor agonists
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Towards sigma1 receptor agonists as neuroprotective agents. Preparation, configurational assignment and in vitro biological profile
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“Fit-for-purpose” development of analytical and (semi)preparative enantioselective high performance liquid and supercritical fluid chromatography for the access to a novel sigma1 receptor agonist.
Get PDFA rapid and straightforward screening protocol of chiral stationary phases (CSPs) in HPLC and SFC resulted in three different methods “fit-for-purpose”, i.e. analysis and scale-up to semi-preparative enantioselective chromatography. The efficient use of these three methods allowed expedited preparation of an important drug discovery target, (R/S)-1, a potent new sigma 1 ( σ1) receptor agonist. The approach taken resulted in significant savings of both time and labor for the isolation of enantiomers compared to the development of a stereo-selective synthesis.The enantiomers of 1 have been isolated allowing studies of their chirooptical properties and an in-deep comparative examination of the pharmacological profile for the individual enantiomers
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