4487-56-3Relevant articles and documents
FUSED IMIDAZOLE COMPOUNDS
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Page/Page column 80, (2015/09/23)
The present invention provides compounds represented by formula (I), pharmaceutically acceptable salts thereof, N-oxides thereof, solvates thereof or prodrugs thereof (wherein the characters are as defined in the description). The compounds represented by formula (I) have affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 (GABAA α5) and act as GABAA α5 negative allosteric modulators (GABAA α5 NAM), so that they are useful in the prevention and/or treatment of diseases which are related to the GABAA α5 such as Alzheimer's disease.
Novel 2,4,5-trisubstituted pyridines as key intermediates for the preparation of the TSPO ligand 6-F-PBR28: Synthesis and full 1H and 13C NMR characterization
Damont, Annelaure,Lemee, Frederic,Raggiri, Guillaume,Dolle, Frederic
, p. 404 - 410 (2014/04/17)
As part of our ongoing research for molecular structures binding to the translocator protein (TSPO 18 kDa), we investigated the preparation of a number of new 2,4,5-trisubstituted pyridines as novel building blocks. In particular, 5-amino-2-halo-4-phenoxypyridines (11, 12, 13) were designed as key intermediates for the synthesis of the recently developed TSPO ligand 6-F-PBR28 and its fluorine-18-labeled version for positron emission tomography, 6-[ 18F]F-PBR28. We hereby report the chemical preparation as well as the 1H and 13C NMR spectroscopic data of polysubstituted pyridines 2, 3, 4, 5, 6, 7, 7b, 8, 9, 10, 11, 12, 13, 14. The latter demonstrates dramatic changes in electron density repartition of the aromatic ring upon substitution.
Discovery of aminofurazan-azabenzimidazoles as inhibitors of rho-kinase with high kinase selectivity and antihypertensive activity
Stavenger, Robert A.,Cui, Haifeng,Dowdell, Sarah E.,Franz, Robert G.,Gaitanopoulos, Dimitri E.,Goodman, Krista B.,Hilfiker, Mark A.,Ivy, Robert L.,Leber, Jack D.,Marino Jr., Joseph P.,Oh, Hye-Ja,Viet, Andrew Q.,Xu, Weiwei,Ye, Guosen,Zhang, Daohua,Zhao, Yongdong,Jolivette, Larry J.,Head, Martha S.,Semus, Simon F.,Elkins, Patricia A.,Kirkpatrick, Robert B.,Dul, Edward,Khandekar, Sanjay S.,Yi, Tracey,Jung, David K.,Wright, Lois L.,Smith, Gary K.,Behm, David J.,Doe, Christopher P.,Bentley, Ross,Chen, Zunxuan X.,Hu, Erding,Lee, Dennis
, p. 2 - 5 (2007/10/03)
The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension. Despite many available treatments, hypertension remains a prevalent problem. In fact, some 30% of hypertensive patients are unable to reach their blood pressure goals. Thus, a new anti-hypertensive treatment, which acts on a broader patient population, would be an important addition to existing treatments. A number of vasoconstrictive agents, including angiotensin II, endothelin-1, and urotensin-II, exert their effect through RhoA and the downstream kinase Rho-kinase (ROCK1).1 Because of its central role in the control of smooth muscle contraction, inhibition of ROCK1 could lead to a more broadly efficacious anti-hypertensive agent.2 ROCK1 inhibitors have been shown to relax vascular smooth muscle and lower blood pressure in several animal models of hypertension.3 Therefore, we began an effort to identify potent ROCK1 inhibitors with pharmacokinetic profiles consistent with once daily oral dosing.
