1361232-72-5Relevant articles and documents
Activating Pyrimidines by Pre-distortion for the General Synthesis of 7-Aza-indazoles from 2-Hydrazonylpyrimidines via Intramolecular Diels-Alder Reactions
Le Fouler, Vincent,Chen, Yu,Gandon, Vincent,Bizet, Vincent,Salomé, Christophe,Fessard, Thomas,Liu, Fang,Houk,Blanchard, Nicolas
, p. 15901 - 15909 (2019/10/22)
Pyrimidines are almost unreactive partners in Diels-Alder cycloadditions with alkenes and alkynes, and only reactions under drastic conditions have previously been reported. We describe how 2-hydrazonylpyrimidines, easily obtained in two steps from commercially available 2-halopyrimidines, can be exceptionally activated by trifluoroacetylation. This allows a Diels-Alder cycloaddition under very mild reaction conditions, leading to a large diversity of aza-indazoles, a ubiquitous scaffold in medicinal chemistry. This reaction is general and scalable and has an excellent functional group tolerance. A straightforward synthesis of a key intermediate of Bayer's Vericiguat illustrates the potential of this cycloaddition strategy. Quantum mechanical calculations show how the simple N-trifluoroacetylation of 2-hydrazonylpyrimidines distorts the substrate into a transition-state-like geometry that readily undergoes the intramolecular Diels-Alder cycloaddition.
Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure
Follmann, Markus,Ackerstaff, Jens,Redlich, Gorden,Wunder, Frank,Lang, Dieter,Kern, Armin,Fey, Peter,Griebenow, Nils,Kroh, Walter,Becker-Pelster, Eva-Maria,Kretschmer, Axel,Geiss, Volker,Li, Volkhart,Straub, Alexander,Mittendorf, Joachim,Jautelat, Rolf,Schirok, Hartmut,Schlemmer, Karl-Heinz,Lustig, Klemens,Gerisch, Michael,Knorr, Andreas,Tinel, Hanna,Mondritzki, Thomas,Trübel, Hubert,Sandner, Peter,Stasch, Johannes-Peter
, p. 5146 - 5161 (2017/06/28)
The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-Activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.
BICYCLIC AZA HETEROCYCLES, AND USE THEREOF
-
Paragraph 0694; 0695; 0696, (2014/06/11)
The present application relates to novel bicyclic azaheterocycles, to processes for preparation thereof, to the use thereof, alone or in combinations, for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of cardiovascular disorders.
SUBSTITUTED ANNULATED PYRIMIDINES AND TRIAZINES, AND USE THEREOF
-
Paragraph 1010 - 1014, (2014/12/09)
The present application relates to novel substituted fused pyrimidines and triazines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.
RING-FUSED PYRIMIDINES AND TRIAZINES AND USE THEREOF FOR THE TREATMENT AND/OR PROPHYLAXIS OF CARDIOVASCULAR DISEASES
-
Paragraph 0323, (2014/12/09)
The present application relates to novel fused pyrimidines and triazines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.
Process for preparing substituted 5-fluoro-1H-pyrazolopyridines
-
Paragraph 0188; 0189; 0190, (2013/06/26)
The present application relates to a novel and efficient process for preparing novel substituted 5-fluoro-1H-pyrazolopyridines of the formula (VI) which are suitable as an intermediate for production of medicaments and for production of medicaments for tr
Substituted annellated pyrimidines and use thereof
-
Paragraph 1461; 1462; 1463; 1464;1465, (2014/02/15)
The present application relates to novel substituted annellated pyrimidines, methods for production thereof, use thereof alone or in combinations for treating and/or preventing diseases and use thereof for the production of medicinal products for treating
METHOD FOR THE PRODUCTION OF 5-FLUORO-1H-PYRAZOLO[3,4-B]PYRIDINE-3-CARBONITRILE
-
Paragraph 0054 - 0057, (2013/08/28)
The present invention relates to a process for preparing 5-fluoro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile of the formula (I) which serves as a synthesis intermediate for production of medicaments, especially for production of medicaments for treatment a
