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10.1002/cmdc.200900014 http://scihub22266oqcxt.onion/10.1002/cmdc.200900014 19263460!ä!19263460 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\19263460.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       ChemMedChem 2009 ; 4 (5): 853-65 Nephropedia Template TP {{tp|p=19263460|t=2009. Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension |pdf=|usr=}}{{19263460}} gab.com Text Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension JO: ChemMedChem http://www.kidney.de/pget.php?&tw=1&pmid=19263460 #FOAvip Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impairments of the NO-sGC signaling pathway have been implicated in the pathogenesis of cardiovascular and other diseases. Direct stimulation of sGC represents a promising therapeutic strategy particularly for the treatment of pulmonary hypertension (PH), a disabling disease associated with a poor prognosis. Previous sGC stimulators such as the pyrazolopyridines BAY 41-2272 and BAY 41-8543 demonstrated beneficial effects in experimental models of PH, but were associated with unfavorable drug metabolism and pharmacokinetic (DMPK) properties. Herein we disclose an extended SAR exploration of this compound class to address these issues. Our efforts led to the identification of the potent sGC stimulator riociguat, which exhibits an improved DMPK profile and exerts strong effects on pulmonary hemodynamics and exercise capacity in patients with PH. Riociguat is currently being investigated in phase III clinical trials for the oral treatment of PH. Twit Text FOAVip Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension ????ChemMedChem http://www.kidney.de/pget.php?&tw=1&pmid=19263460 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=19263460 #FOAvip English Wikipedia <ref>{{Cite pmid|19263460}}</ref> Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension #MMPMID19263460 Mittendorf J; Weigand S; Alonso-Alija C; Bischoff E; Feurer A; Gerisch M; Kern A; Knorr A; Lang D; Muenter K; Radtke M; Schirok H; Schlemmer KH; Stahl E; Straub A; Wunder F; Stasch JP ChemMedChem 2009[May]; 4 (5): 853-65 PMID19263460show ga Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impairments of the NO-sGC signaling pathway have been implicated in the pathogenesis of cardiovascular and other diseases. Direct stimulation of sGC represents a promising therapeutic strategy particularly for the treatment of pulmonary hypertension (PH), a disabling disease associated with a poor prognosis. Previous sGC stimulators such as the pyrazolopyridines BAY 41-2272 and BAY 41-8543 demonstrated beneficial effects in experimental models of PH, but were associated with unfavorable drug metabolism and pharmacokinetic (DMPK) properties. Herein we disclose an extended SAR exploration of this compound class to address these issues. Our efforts led to the identification of the potent sGC stimulator riociguat, which exhibits an improved DMPK profile and exerts strong effects on pulmonary hemodynamics and exercise capacity in patients with PH. Riociguat is currently being investigated in phase III clinical trials for the oral treatment of PH. |Administration, Oral[MESH] |Animals[MESH] |Dogs[MESH] |Drug Discovery[MESH] |Female[MESH] |Guanylate Cyclase/metabolism[MESH] |Hypertension, Pulmonary/drug therapy[MESH] |Morpholines/chemistry/pharmacology[MESH] |Nitric Oxide/metabolism[MESH] |Pyrazoles/chemistry/pharmacology[MESH] |Pyridines/chemistry/pharmacology[MESH] |Pyrimidines/chemical synthesis/*chemistry/pharmacokinetics/pharmacology[MESH] |Rabbits[MESH] |Rats[MESH] |Receptors, Cytoplasmic and Nuclear/*agonists/metabolism[MESH] |Signal Transduction[MESH] |Soluble Guanylyl Cyclase[MESH]Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of sol(epmc).pdf DeepDyve Pubget Overpricing