Pharmacotherapy of Systemic Sclerosis: Focus on Bosentan

Abstract

Systemic sclerosis is manifested by the massive deposition of collagen within various organ systems. Endothelin-1 has taken a pivotal role as not only a potent vasoconstrictor, but also as a profibrotic intermediary. Bosentan is proving to be a viable therapeutic option in alleviating manifestations of systemic sclerosis other than pulmonary hypertension. There are many reports in the literature profiling bosentan's safety, efficacy and tolerability in patients. In addition, it has greatly improved patients’ quality of life, reduced the number of hospitalizations and increased the time to clinical worsening of the disease. The clinical indications for use of bosentan in a wide array of patients has served as a valuable asset in the medical management of systemic sclerosis.

Stability-Indicating Gradient RP-LC Method for the Determination of Process and Degradation Impurities in Bosentan Monohydrate: An Endothelin Receptor Antagonist

“…It is the first orally active drug approved by United States Food and Drug Administrative as Tracleer (65 mg and 125 mg) for the successful treatment of pulmonary arterial hypertension (PAH). Tracleer improves the exercise ability and decreases the rate of clinical worsening in patients with WHO Class III or IV symptoms of PAH, by blocking the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects [1][2][3][4][5][6][7][8]. Further Tracleer has been demonstrated to be effective in remodeling the pulmonary vascular tree through several mechanisms including vasodilatation, antifibrotic and antithrombotic actions [9].…”

Facile One-Pot Process for Large-Scale Production of Highly Pure Bosentan Monohydrate, an Endothelin Receptor Antagonist

“…Tracleer improves the exercise ability and decreases the rate of clinical worsening in patients with WHO Class III or IV symptoms of PAH by blocking the binding of endothelin to its receptors, thereby negating endothelin’s deleterious effects. Further, it has been demonstrated to be effective in remodeling the pulmonary vascular tree through several mechanisms including vasodilatation and antifibrotic and antithrombotic actions . The first synthetic approach reported for 1 involved the condensation of dichloro compound 2 with sulfonamide 3 in dimethylsulfoxide (DMSO) to provide p - tert -butyl- N -[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzenesulfonamide ( 5 ).…”