Efficient Synthesis of a Highly Selective NPY-5 Receptor Antagonist:  A Drug Candidate for the Treatment of Obesity

2006 ◽  
Vol 10 (4) ◽  
pp. 822-828 ◽  
Author(s):  
Takahiro Itoh ◽  
Shinji Kato ◽  
Nobuaki Nonoyama ◽  
Toshihiro Wada ◽  
Kenji Maeda ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Drug Candidate ◽  
Efficient Synthesis ◽  
Treatment Of Obesity

scholarly journals The Leukotriene Receptor Antagonist Montelukast Attenuates Neuroinflammation and Affects Cognition in Transgenic 5xFAD Mice

2021 ◽  
Vol 22 (5) ◽  
pp. 2782 ◽  
Author(s):  
Johanna Michael ◽  
Julia Zirknitzer ◽  
Michael Stefan Unger ◽  
Rodolphe Poupardin ◽  
Tanja Rieß ◽  
...  
Keyword(s):  
T Cells ◽  
Receptor Antagonist ◽  
Cd8 T Cells ◽  
Disease Model ◽  
Cognitive Outcome ◽  
Drug Candidate ◽  
Potential Drug ◽  
Leukotriene Receptor Antagonist ◽  
Leukotriene Receptor ◽  
5Xfad Mice

Alzheimer’s disease (AD) is the most common form of dementia. In particular, neuroinflammation, mediated by microglia cells but also through CD8+ T-cells, actively contributes to disease pathology. Leukotrienes are involved in neuroinflammation and in the pathological hallmarks of AD. In consequence, leukotriene signaling—more specifically, the leukotriene receptors—has been recognized as a potential drug target to ameliorate AD pathology. Here, we analyzed the effects of the leukotriene receptor antagonist montelukast (MTK) on hippocampal gene expression in 5xFAD mice, a commonly used transgenic AD mouse model. We identified glial activation and neuroinflammation as the main pathways modulated by MTK. The treatment increased the number of Tmem119+ microglia and downregulated genes related to AD-associated microglia and to lipid droplet-accumulating microglia, suggesting that the MTK treatment targets and modulates microglia phenotypes in the disease model compared to the vehicle. MTK treatment further reduced infiltration of CD8+T-cells into the brain parenchyma. Finally, MTK treatment resulted in improved cognitive functions. In summary, we provide a proof of concept for MTK to be a potential drug candidate for AD and provide novel modes of action via modulation of microglia and CD8+ T-cells. Of note, 5xFAD females showed a more severe pathology, and in consequence, MTK treatment had a more pronounced effect in the females compared to the males. The effects on neuroinflammation, i.e., microglia and CD8+ T-cells, as well as the effects on cognitive outcome, were dose-dependent, therefore arguing for the use of higher doses of MTK in AD clinical trials compared to the approved asthma dose.

Late-Stage Sulfoximination: Improved Synthesis of the Anticancer Drug Candidate Atuveciclib

Synthesis ◽  
2018 ◽  
Vol 51 (04) ◽  
pp. 971-975 ◽  
Author(s):  
Vincent Reboul ◽  
Thomas Glachet ◽  
Xavier Franck
Keyword(s):  
Anticancer Drug ◽  
Late Stage ◽  
Drug Candidate ◽  
Efficient Synthesis ◽  
Reaction Conditions

An efficient synthesis of racemic atuveciclib was accomplished in five steps with an excellent 51% overall yield, using cheap reagents and mild reaction conditions. The key sulfoximination reaction was realized during the last step of the synthesis from the corresponding sulfide.

scholarly journals Efficient and improved synthesis of Telmisartan

2010 ◽  
Vol 6 ◽  
Author(s):  
A Sanjeev Kumar ◽  
Samir Ghosh ◽  
G N Mehta
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Reductive Amination ◽  
Cross Coupling ◽  
Efficient Synthesis ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Antagonist

An efficient synthesis of the angiotensin II receptor antagonist Telmisartan (1) is presented involving a cross coupling of 4-formylphenylboronic acid 10 with 2-(2-bromophenyl)-4,4-dimethyl-2-oxazoline (11) as the key step (90% yield). The benzimidazole moiety 15 was constructed regioselectively via a reductive amination-condensation sequence, replacing the alkylation of the preformed benzimidazole step in the previously published route. This methodology overcomes many of drawbacks associated with previously reported syntheses.

ChemInform Abstract: Efficient Synthesis of Losartan, a Nonpeptide Angiotensin II Receptor Antagonist.

ChemInform ◽  
1995 ◽  
Vol 26 (16) ◽  
pp. no-no
Author(s):  
R. D. LARSEN ◽  
A. O. KING ◽  
C. Y. CHEN ◽  
E. G. CORLEY ◽  
B. S. FOSTER ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Efficient Synthesis ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Antagonist
Sign in / Sign up

Export Citation Format

Share Document