553631-31-5Relevant articles and documents
HETEROCYCLIC COMPOUNDS, MEDICAMENTS CONTAINING SAID COMPOUNDS, USE THEREOF AND PROCESSES FOR THE PREPARATION THEREOF
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Page/Page column 45, (2013/05/22)
The present invention relates to compounds of general formula (I) and the tautomers and the salts thereof, particularly the pharmaceutically acceptable salts thereof with inorganic or organic acids and bases, which have valuable pharmacological properties, particularly an inhibitory effect on epithelial sodium channels, the use thereof for the treatment of diseases, particularly diseases of the lungs and airways.
Discovery of a selective allosteric M1 receptor modulator with suitable development properties based on a quinolizidinone carboxylic acid scaffold
Kuduk, Scott D.,Chang, Ronald K.,Di Marco, Christina N.,Pitts, Daniel R.,Greshock, Thomas J.,Ma, Lei,Wittmann, Marion,Seager, Matthew A.,Koeplinger, Kenneth A.,Thompson, Charles D.,Hartman, George D.,Bilodeau, Mark T.,Ray, William J.
experimental part, p. 4773 - 4780 (2011/09/20)
One approach to ameliorate the cognitive decline in Alzheimer's disease (AD) has been to restore neuronal signaling from the basal forebrain cholinergic system via the activation of the M1 muscarinic receptor. A number of nonselective M1 muscarinic agonists have previously shown positive effects on cognitive behaviors in AD patients, but were limited due to cholinergic adverse events thought to be mediated by the activation of the M2 to M5 subtypes. One strategy to confer selectivity for M1 is the identification of positive allosteric modulators, which would target an allosteric site on the M1 receptor rather than the highly conserved orthosteric acetylcholine binding site. Quinoline carboxylic acids have been previously identified as highly selective M1 positive allosteric modulators with good pharmacokinetic and in vivo properties. Herein is described the optimization of a novel quinolizidinone carboxylic acid scaffold with 4-cyanopiperidines being a key discovery in terms of enhanced activity. In particular, modulator 4i gave high plasma free fractions, enhanced central nervous system (CNS) exposure, was efficacious in a rodent in vivo model of cognition, and afforded good physicochemical properties suitable for further preclinical evaluation.
Phenylacetamides as selective α-1A adrenergic receptor antagonists
Patane, Michael A.,DiPardo, Robert M.,Newton, Randall C.,Price, RoseAnn P.,Broten, Theodore P.,Chang, Raymond S.L.,Ransom, Richard W.,Di Salvo, Jerry,Nagarathnam, Dhanapalan,Forray, Carlos,Gluchowski, Charles,Bock, Mark G.
, p. 1621 - 1624 (2007/10/03)
A novel class of potent and selective α-1a receptor antagonists has been identified. The structures of these antagonists were derived from truncating the 4-aryl dihydropyridine subunit present in known α-1a antagonists. The design principles which led to the discovery of substituted phenylacetamides, the synthesis and SAR of key analogues, and the results of select in vitro and in vivo studies are described. (C) 2000 Elsevier Science Ltd. All rights reserved.
