scholarly journals Exploring the binding mechanisms of PDE5 with chromeno[2,3-c]pyrrol-9(2H)-one by theoretical approaches

RSC Advances ◽  
2018 ◽  
Vol 8 (53) ◽  
pp. 30481-30490 ◽  
Author(s):  
Xianfeng Huang ◽  
Peng Xu ◽  
Yijing Cao ◽  
Li Liu ◽  
Guoqiang Song ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Pulmonary Arterial Hypertension ◽  
Drug Target ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Theoretical Approaches ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type ◽  
Binding Mechanisms ◽  
Important Drug

Cyclic nucleotide phosphodiesterase type 5 (PDE5) is exclusively specific for the cyclic guanosine monophosphate (cGMP), and PDE5 is an important drug target for the treatment of erectile dysfunction and pulmonary arterial hypertension (PAH).

Synthesis of isotope – labeled selective PDE5 inhibitor sildenafil (UK 92480-10)

2018 ◽  
Vol 106 (10) ◽  
pp. 851-855
Author(s):  
R. Sekhar Bolla ◽  
Kali Charan Gulipalli ◽  
N. Murthy Gandikota ◽  
Srinu Bodige ◽  
I. V. Kasi Viswanath
Keyword(s):  
Erectile Dysfunction ◽  
Pulmonary Arterial Hypertension ◽  
Pde5 Inhibitor ◽  
Cyclic Guanosine Monophosphate ◽  
Selective Inhibitor ◽  
Guanosine Monophosphate ◽  
Isotopic Abundance ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type ◽  
Male Erectile Dysfunction

Abstract Sildenfil a vasodilating agent is a selective inhibitor of cyclic guanosine monophosphate – specific phosphodiesterase type 5 which is used for the treatment of male erectile dysfunction and pulmonary arterial hypertension. We presented a detailed approach for the synthesis of [2H3]sildenafil, [2H8]sildenafil and N-desmethyl [2H8]sildenafil. By using the approach we successfully synthesized [2H3]sildenafil, [2H8]sildenafil and N-desmethyl [2H8]sildenafil with good isotopic abundance.

scholarly journals Treatment Selection in Pulmonary Arterial Hypertension: Phosphodiesterase Type 5 Inhibitors versus Soluble Guanylate Cyclase Stimulator

2018 ◽  
Vol 13 (1) ◽  
pp. 35 ◽  
Author(s):  
Hiroshi Watanabe ◽  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Pharmacological Action ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type

Pulmonary arterial hypertension is a chronic and life-threatening disease that if left untreated is fatal. Current therapies include stimulating the nitric oxide–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate axis, improving the prostacyclin pathway and inhibiting the endothelin pathway. Phosphodiesterase type 5 inhibitors, such as sildenafil, and the sGC stimulator riociguat are currently used in the treatment of pulmonary arterial hypertension. This article discusses the similarities and differences between phosphodiesterase type 5 inhibitors and sGC stimulator based on pharmacological action and clinical trials, and considers which is better for the treatment of pulmonary arterial hypertension.

scholarly journals Nitrogen oxide biochemical pathway in pulmonary arterial hypertension therapy and REPLACE trial results

2018 ◽  
Vol 15 (2) ◽  
pp. 72-76 ◽  
Author(s):  
A A Shmalts ◽  
S V Gorbachevsky
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Controlled Trial ◽  
Pde5 Inhibitor ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Controlled Study ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Hypertension Therapy

Endogen nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) deficiency in pulmonary vessels walls plays essential role in pulmonary arterial hypertension (PAH) pathogenesis. Soluble guanylate cyclase stimulator riociguat and phosphodiesterase-5 (PDE5) inhibitor sildenafil increase cGMP content and have proven clinical efficacy in PAH treatment. The potentially beneficial mechanisms of riociguat mechanism of action include endogen NO independence in cGMP synthesis and its independence from other phosphodiesterase isoferments (other than PDE5). Clinical options, safety and effectiveness of iPDE5 - riociguat transition in patients with PAH were for the first time shown in non-controlled study RESPITE and the assessment is continued in randomized placebo-controlled trial REPLACE.

scholarly journals Current Modulation of Guanylate Cyclase Pathway Activity—Mechanism and Clinical Implications

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3418
Author(s):  
Grzegorz Grześk ◽  
Alicja Nowaczyk
Keyword(s):  
Guanylate Cyclase ◽  
Natriuretic Peptides ◽  
Soluble Guanylate Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Pharmacological Intervention ◽  
First Line ◽  
Phosphodiesterase Type ◽  
Activity Mechanism

For years, guanylate cyclase seemed to be homogenic and tissue nonspecific enzyme; however, in the last few years, in light of preclinical and clinical trials, it became an interesting target for pharmacological intervention. There are several possible options leading to an increase in cyclic guanosine monophosphate concentrations. The first one is related to the uses of analogues of natriuretic peptides. The second is related to increasing levels of natriuretic peptides by the inhibition of degradation. The third leads to an increase in cyclic guanosine monophosphate concentration by the inhibition of its degradation by the inhibition of phosphodiesterase type 5. The last option involves increasing the concentration of cyclic guanosine monophosphate by the additional direct activation of soluble guanylate cyclase. Treatment based on the modulation of guanylate cyclase function is one of the most promising technologies in pharmacology. Pharmacological intervention is stable, effective and safe. Especially interesting is the role of stimulators and activators of soluble guanylate cyclase, which are able to increase the enzymatic activity to generate cyclic guanosine monophosphate independently of nitric oxide. Moreover, most of these agents are effective in chronic treatment in heart failure patients and pulmonary hypertension, and have potential to be a first line option.

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