A series of derivatives of 2,4-dihydroxy-3-propylacetophenone(1) were prepared and examined for their ability to block leukotriene D4 (LTD4) induced contraction of guinea pig ileum. Straight-chain carboxylic acids where the carboxyl group was separated from the acetophenone moiety by varying numbers of methylenes were evaluated, and maximum activity was obtained with the pentamethylene acid (6). Examination of ring substitution showed that the 2-propyl-3-hydroxy-4-acetyl substitution pattern was required for maximum LTD4 antagonist activity. Additional chain terminal groups were examined, and the acidic 5-tetrazolyl group separated from the acetophenone moiety by four to seven methylenes (26, 23, 27, 28) gave excellent in vitro and in vivo activities. Compound 26 (LY171883) had the best balance of in vitro and in vivo activity. It lacked bronchospastic activity at the doses administered and has been chosen for clinical evaluation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm00387a018 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Singlets-Driven Photoredox Catalysts: Transforming Noncatalytic Red Fluorophores to Efficient Catalysts.
JACS Au
December 2024
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, United States.
Red-light absorbing photoredox catalysts offer potential advantages for large-scale reactions, expanding the range of usable substrates and facilitating bio-orthogonal applications. While many red-light absorbing/emitting fluorophores have been developed recently, functional red-light absorbing photoredox catalysts are scarce. Many photoredox catalysts rely on long-lived triplet excited states (triplets), which can efficiently engage in single electron transfer (SET) reactions with substrates.
View Article and Find Full Text PDFOnset and long-term duration of immunity provided by a single vaccination with recombinant a Marek's disease virus with REV-LTR insertion.
Front Vet Sci
December 2024
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
Marek's Disease (MD), caused by Marek's disease virus (MDV), is a highly contagious lymphoproliferative disease in poultry. Despite the fact that MD has been effectively controlled by vaccines, the virulence of field isolates of MDV has continued to evolve, becoming more virulent under the immune pressure of vaccines. Our previous research has confirmed that the recombinant rMDV strain with REV-LTR insertion can be used as a live attenuated vaccine candidate.
View Article and Find Full Text PDFGe Epitaxy at Ultralow Growth Temperatures Enabled by a Pristine Growth Environment.
ACS Appl Electron Mater
December 2024
Institute of Semiconductor and Solid State Physics, Johannes Kepler University Linz, Altenberger Straße 69, 4040, Linz, Austria.
Germanium (Ge), the next-in-line group-IV material, bears great potential to add functionality and performance to next-generation nanoelectronics and solid-state quantum transport based on silicon (Si) technology. Here, we investigate the direct epitaxial growth of two-dimensional high-quality crystalline Ge layers on Si deposited at ultralow growth temperatures ( = 100-350 °C) and pristine growth pressures (≲10 mbar). First, we show that a decreasing does not degrade the crystal quality of homoepitaxial Ge/Ge(001) by comparing the point defect density using positron annihilation lifetime spectroscopy.
View Article and Find Full Text PDFBurden of comorbidities in heart failure patients in Türkiye.
Turk J Med Sci
December 2024
Department of Cardiology, Faculty of Medicine, Mersin University, Mersin, Turkiye.
Background/aim: Heart failure (HF) is associated with a wide range of comorbidities that negatively impact clinical outcomes and cause high economic burden. We aimed to evaluate the frequency and burden of comorbidities in HF patients in Türkiye and their relationships with patients' demographic characteristics.
Materials And Methods: Based on ICD-10 codes in the national electronic database of the Turkish Ministry of Health covering the entire population of Türkiye (n = 85,279,553) from 1 January 2016 to 31 December 2022, data on the prevalence of comorbidities in HF patients were obtained.
Investigating the effects of co-exposure to noise and benzene on serum oxidative stress in rat.
Toxicol Rep
December 2024
Department of Occupational Health and Ergonomic, Qazvin Medical University, Qazvin, Iran.
Occupational exposures are generally complex, workers are exposed with more than one hazardous agent in work environment. Combined exposure to noise and benzene is common in occupational environments. Sub-acute exposure to benzene vapors can induce oxidative stress in serum.
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!