1163271-54-2

Upstream product

• 2521-24-6 4-chlorothiobenzamide 
• 22042-73-5 4-(2-hydroxy-ethoxy)-benzaldehyde 
• 112906-84-0 2-[4-(2-hydroxyethoxy)benzylidene]malononitrile 
• 544417-40-5 Capadenoson 

Downstream Products

• 1239234-60-6 2-((2-(4-chlorophenyl)-1,3-thiazol-4-ylmethyl)sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)-6-(piperidin-1-yl)pyridine-3,5-dicarbonitrile 
• 1239234-36-6 2-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulphanyl)-4-[4-(2-hydroxyethoxy)phenyl]-6-(pyrrolidin-1-yl)pyridine-3,5-dicarbonitrile 
• 1239234-46-8 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}thio)-6-(diethylamino)-4-(4-(2-hydroxy-ethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239234-52-6 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-6-(cyclopropylamino)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239234-54-8 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-6-(cyclobutylamino)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239234-44-6 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}thio)-6-(ethyl(methyl)amino)-4-(4-(2-hydroxy-ethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239234-98-0 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)-6-((2,2,2-trifluoroethyl)amino)pyridine-3,5-dicarbonitrile 
• 1239234-50-4 2-(azetidin-1-yl)-6-((2-(4-chlorophenyl)-1,3-thiazol-4-ylmethyl)sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239234-40-2 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}thio)-6-(ethylamino)-4-(4-(2-hydroxy-ethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239234-48-0 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}thio)-4-(4-(2-hydroxyethoxy)phenyl)-6-(isopropylamino)pyridine-3,5-dicarbonitrile 
• 1239234-42-4 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}thio)-6-(dimethylamino)-4-(4-(2-hydroxy-ethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239234-86-6 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-6-(3,3-difluoropyrrolidin-1-yl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239235-06-3 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-6-(ethyl(2,2,2-trifluoroethyl)amino)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile 
• 1239235-04-1 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)-6-(methyl(2,2,2-trifluoroethyl)amino)pyridine-3,5-dicarbonitrile 

Relevant academic research and scientific papers

PROCESS FOR THE PREPARATION OF 2-{4-[2-({[2-(4-CHLOROPHENYL)-1,3-THIAZOL-4-YL]METHYL}SULFANYL)-3,5-DICYAN0-6-(PYRROLIDIN-1-YL)PYRIDIN-4-YL]PHENOXY}ETHYL-L-ALANYL-L-ALANINATE MONOHYDROCHLORIDE

The present application relates to a novel and improved process for preparing the compound 2-{4-[2-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulphanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl]phenoxy}ethyl-L-alanyl L-alaninate monohydrochloride of the formula (I) to novel precursors for its preparation, and to the preparation and use of crystal modification I of 2-{4-[2-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulphanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl]phenoxy}-ethyl-L-alanyl L-alaninate monohydrochloride of the formula (I).

Neladenoson Bialanate Hydrochloride: A Prodrug of a Partial Adenosine A1 Receptor Agonist for the Chronic Treatment of Heart Diseases

Adenosine is known to be released under a variety of physiological and pathophysiological conditions to facilitate the protection and regeneration of injured ischemic tissues. The activation of myocardial adenosine A1 receptors (A1Rs) has been shown to inhibit myocardial pathologies associated with ischemia and reperfusion injury, suggesting several options for new cardiovascular therapies. When full A1R agonists are used, the desired protective and regenerative cardiovascular effects are usually overshadowed by unintended pharmacological effects such as induction of bradycardia, atrioventricular (AV) blocks, and sedation. These unwanted effects can be overcome by using partial A1R agonists. Starting from previously reported capadenoson we evaluated options to tailor A1R agonists to a specific partiality range, thereby optimizing the therapeutic window. This led to the identification of the potent and selective agonist neladenoson, which shows the desired partial response on the A1R, resulting in cardioprotection without sedative effects or cardiac AV blocks. To circumvent solubility and formulation issues for neladenoson, a prodrug approach was pursued. The dipeptide ester neladenoson bialanate hydrochloride showed significantly improved solubility and exposure after oral administration. Neladenoson bialanate hydrochloride is currently being evaluated in clinical trials for the treatment of heart failure.

SUBSTITUTED AZABICYCLIC COMPOUNDS AND THE USE THEREOF

The present application relates to novel substituted pyrrolopyridine, pyrazolopyridine and isoxazolopyridine derivatives, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, preferably for the treatment and/or prevention of cardiovascular disorders.

2-ALKOXY-SUBSTITUTED DICYANOPYRIDINES AND THEIR USE

The present application relates to novel 2-alkoxy-substituted dicyanopyridines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prevention of cardiovascular disorders.

ALKYLAMINO-SUBSTITUTED DICYANOPYRIDINES AND THEIR AMINO ACID ESTER PRODRUGS

The present application relates to novel 6-alkylamino-substituted dicyanopyridines, to their amino acid ester prodrugs, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prevention of cardiovascular disorders.