madman
Super Moderator
Abstract
Tadalafil, Cialis, Eli Lilly & Co./ICOS, (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12ahexahydropyrazino[10,20:1,6] pyrido[3,4-b]indole-1,4-dione, was first discovered in 2003. It was reported to have high diastereospecificity for phosphodiesterase 5 (PDE5) inhibitions. The cis-(6R, 12aR) enantiomer is the most active enantiomer. Tadalafil showed PDE5 inhibition with IC50 =5 nM. It possesses high selectivity for PDE5 versus PDE1-4 and PDE6. Tadalafil is more selective to PDE5 against PDE6 whereas sildenafil, another commercially available PDE5 inhibitor shows similar potencies to inhibit PDE5 and PDE6. Tadalafil is used for the treatment of male erectile dysfunction (MED), prostatic benign hyperplasia (PBH) signs and symptoms, and pulmonary arterial hypertension (PAH). Adcirca, another name for tadalafil, is used to treat PAH and improve exercise capacity. Recent clinical studies suggest the use of tadalafil for nonurological applications, including circulatory disorders (ischemia injury, myocardial infarction, cardiac hypertrophy, cardiomyopathy, heart failure, and stroke), neurodegenerative disorders, and cognitive impairment conditions. This review discusses tadalafil and its analogs reported in the past 15 years. It discusses synthetic pathways, structural activity relationships, existing and future pharmacological indications of tadalafil, and its analogs. This work can help medicinal chemists develop novel PDE5 inhibitors with wider therapeutic indications.
5 | CONCLUSION
In conclusion, tadalafil is an important drug lead investigated by researchers worldwide for MED. Tadalafil is a unique member of the PDE5 inhibitors family, it has a characteristic chemical scaffold (tetrahydro-β-carboline) and desired pharmacokinetics properties (essentially longer half-life). Tadalafil significantly improved psychological outcomes. Furthermore, the patients and their partners preferred tadalafil over sildenafil, and no significant difference was found in the adherence and persistence rates between tadalafil and sildenafil (Gong et al., 2017). Despite sildenafil being the first in the PDE5 inhibitors family to offer a new approach in the field of treating ED, tadalafil seems to introduce new perspectives for the treatment and cure of ED. Tadalafil's discovery stimulated further research on the discovery of other significant analogs with novel biological activities. It is anticipated that in the near future, there will be more promising compounds in terms of efficacy, selectivity, and new targets.
*In this review article, the author worked on presenting the progressions made in the last 15 years in the tadalafil research domain.
*The author hopes it will assist researchers interested in the PDE5 family, PDE5 inhibitors, their approved, investigated, and future applications.
Tadalafil, Cialis, Eli Lilly & Co./ICOS, (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12ahexahydropyrazino[10,20:1,6] pyrido[3,4-b]indole-1,4-dione, was first discovered in 2003. It was reported to have high diastereospecificity for phosphodiesterase 5 (PDE5) inhibitions. The cis-(6R, 12aR) enantiomer is the most active enantiomer. Tadalafil showed PDE5 inhibition with IC50 =5 nM. It possesses high selectivity for PDE5 versus PDE1-4 and PDE6. Tadalafil is more selective to PDE5 against PDE6 whereas sildenafil, another commercially available PDE5 inhibitor shows similar potencies to inhibit PDE5 and PDE6. Tadalafil is used for the treatment of male erectile dysfunction (MED), prostatic benign hyperplasia (PBH) signs and symptoms, and pulmonary arterial hypertension (PAH). Adcirca, another name for tadalafil, is used to treat PAH and improve exercise capacity. Recent clinical studies suggest the use of tadalafil for nonurological applications, including circulatory disorders (ischemia injury, myocardial infarction, cardiac hypertrophy, cardiomyopathy, heart failure, and stroke), neurodegenerative disorders, and cognitive impairment conditions. This review discusses tadalafil and its analogs reported in the past 15 years. It discusses synthetic pathways, structural activity relationships, existing and future pharmacological indications of tadalafil, and its analogs. This work can help medicinal chemists develop novel PDE5 inhibitors with wider therapeutic indications.
5 | CONCLUSION
In conclusion, tadalafil is an important drug lead investigated by researchers worldwide for MED. Tadalafil is a unique member of the PDE5 inhibitors family, it has a characteristic chemical scaffold (tetrahydro-β-carboline) and desired pharmacokinetics properties (essentially longer half-life). Tadalafil significantly improved psychological outcomes. Furthermore, the patients and their partners preferred tadalafil over sildenafil, and no significant difference was found in the adherence and persistence rates between tadalafil and sildenafil (Gong et al., 2017). Despite sildenafil being the first in the PDE5 inhibitors family to offer a new approach in the field of treating ED, tadalafil seems to introduce new perspectives for the treatment and cure of ED. Tadalafil's discovery stimulated further research on the discovery of other significant analogs with novel biological activities. It is anticipated that in the near future, there will be more promising compounds in terms of efficacy, selectivity, and new targets.
*In this review article, the author worked on presenting the progressions made in the last 15 years in the tadalafil research domain.
*The author hopes it will assist researchers interested in the PDE5 family, PDE5 inhibitors, their approved, investigated, and future applications.
