Lead compound 1 was successfully redesigned to provide compounds with improved pharmacokinetic profiles for this series of human urotensin-II antagonists. Replacement of the 2-pyrrolidinylmethyl-3-phenyl-piperidine core of 1 with a substituted N-methyl-2-(1-pyrrolidinyl)ethanamine core as in compound 7 resulted in compounds with improved oral bioavailability in rats. The relationship between stereochemistry and selectivity for hUT over the kappa-opioid receptor was also explored.
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| http://dx.doi.org/10.1016/j.bmcl.2008.05.058 | DOI Listing |
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Integrating network pharmacology and experimental validation to explore the pharmacological mechanism of Astragaloside IV in alleviating urotensin II-mediated renal tubular epithelial cell injury.
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Department of Nephrology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
Renal tubular epithelial cell injury is an important manifestation of chronic kidney disease (CKD). This study aims to explore the mechanism of astragaloside IV (AS-IV) in the treatment of UII-mediated renal tubular epithelial cell injury by integrating network pharmacology and experimental validation. BATMAN, SwissTarget-Prediction and ETCM data bases were used to screen the target proteins of AS-IV.
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Department of Organic Chemistry, State Research Institute Center for Physical Sciences and Technology, Saulėtekio Ave. 3, Vilnius LT-10257, Lithuania. Electronic address:
The cyclic human neuropeptide Urotensin II (hU-II) is an important regulatory peptide found in the central nervous system, cardiovascular system, kidney, etc., however, its conformational structure and dynamics in aqueous solutions have not been studied in detail experimentally. In the present study, the structure of hU-II and the mechanism of its adsorption on the electrochemically roughened Ag electrode are investigated using electrochemical surface-enhanced Raman scattering spectroscopy (EC-SERS) in the voltage range from -1.
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Research Institute of the McGill University Health Centre, Respiratory Program and Meakins-Christie Laboratories, Montreal, Quebec, Canada.
Article Synopsis
- Inherited or sporadic loss of a specific gene can lead to pulmonary lymphangioleiomyomatosis (LAM), a rare lung disease caused by tumor nodules that display characteristics of neural crest and smooth muscle cells.
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Nat Commun
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