Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of migraine. Replacements for the benzodiazepine core of an earlier lead structure 1 including 5-, 6-, and 7-membered lactams were explored. Within the 7-membered ring scaffold, phenyl substitution at various positions afforded the potent (3R)-amino-(6S)-phenyl caprolactam template. The phenylimidazolinone privileged structure gave additional potency enhancements, as 24 showed good potency in both CGRP binding (K(i)=2 nM) and cAMP (IC(50)=4 nM) assays and was orally bioavailable in rats (27%).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2007.06.062 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High-selective platinum and palladium capture using polyamide 6: A potent material for platinum group metals' recovery from spent car catalytic converter.
J Environ Manage
November 2024
Graduate Institute of Environmental Engineering, National Taiwan University, Taipei, 106319, Taiwan; Advanced Research Center for Green Materials Science and Technology, National Taiwan University, Taipei, 106319, Taiwan. Electronic address:
Platinum (Pt) and palladium (Pd) are commonly integrated into automotive catalytic converters to convert harmful emissions into relatively safer substances. Their scarcity has resulted in the rapid development of an industry focused on their recovery. Polyamide 6 (PA6), a microplastic pollutant, is a common industrial material.
View Article and Find Full Text PDFOccurrence and Prioritization of Human Androgen Receptor Disruptors in Sewage Sludges Across China.
Environ Sci Technol
June 2024
College of Sciences, Northeastern University, Shenyang110004, China.
The global practice of reusing sewage sludge in agriculture and its landfill disposal reintroduces environmental contaminants, posing risks to human and ecological health. This study screened sewage sludge from 30 Chinese cities for androgen receptor (AR) disruptors, utilizing a disruptor list from the Toxicology in the 21st Century program (Tox21), and identified 25 agonists and 33 antagonists across diverse use categories. Predominantly, natural products 5α-dihydrotestosterone and thymidine emerged as agonists, whereas the industrial intermediate caprolactam was the principal antagonist.
View Article and Find Full Text PDFSelf-micellizing solid dispersion of tacrolimus: Physicochemical and pharmacokinetic characterization.
Biopharm Drug Dispos
December 2023
Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
The present study was undertaken to develop a self-micellizing solid dispersion (SMSD) of tacrolimus (TAC) to improve the biopharmaceutical properties of TAC. An SMSD formulation of TAC (SMSD/TAC) and amorphous solid dispersion formulation of TAC (ASD/TAC) were prepared with Soluplus , an amphiphilic copolymer, and hydroxypropyl cellulose, respectively. Physicochemical properties were characterized in terms of morphology, crystallinity, storage stability, interaction of TAC with Soluplus , and micelle-forming potency; pharmacokinetic behavior was also evaluated in rats.
View Article and Find Full Text PDF-Caprolactam- and Nylon Oligomer-Degrading Bacterium BS3: Characterization and Potential Use in Bioremediation.
Microorganisms
February 2023
Laboratory of Microbial Enzymology, G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Pushchino Center for Biological Research of the Russian Academy of Sciences, prosp. Nauki 5, 142290 Pushchino, Russia.
-Caprolactam (Caprolactam, CAP), a monomer of the synthetic non-degradable polymer nylon-6, is the major wastewater component in the production of caprolactam and nylon-6. Biological treatment of CAP, using microbes could be a potent alternative to the current waste utilization techniques. This work focuses on the characterization and potential use of caprolactam-degrading bacterial strain BS3 isolated from soils polluted by CAP production wastes.
View Article and Find Full Text PDFFibrinogen/poly(l-lactide-co-caprolactone) copolymer scaffold: A potent adhesive material for urethral tissue regeneration in urethral injury treatment.
Regen Ther
March 2023
Department of Urology, Shanghai Fifth People's Hospital, Fudan University, No. 801 Heqing Road, Minhang District, Shanghai 200240, China.
Since a scarcity of sufficient grafting materials, several complications can arise after urothelial defect reconstruction surgery, including severe hypospadias. Accordingly, developing alternative therapies, such as urethral restoration via tissue engineering are needed. In the present study, we developed a potent adhesive and repairing material using fibrinogen-poly(l-lactide-co-caprolactone) copolymer (Fib-PLCL) nanofiber scaffold to achieve effective urethral tissue regeneration after seeding with epithelial cells on the surface.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!