The use of sulfonylamido pyrimidines incorporating an unsaturated side chain as endothelin receptor antagonists.

Article Details

Citation

Bolli MH, Boss C, Clozel M, Fischli W, Hess P, Weller T

The use of sulfonylamido pyrimidines incorporating an unsaturated side chain as endothelin receptor antagonists.

Bioorg Med Chem Lett. 2003 Mar 10;13(5):955-9.

PubMed ID
12617929 [ View in PubMed
]
Abstract

A series of compounds structurally related to bosentan 1 featuring an unsaturated side chain at position 6 of the core pyrimidine have been studied for their potential to block the ET(A) and ET(B) receptor. Incorporation of a 2-butyne-1,4-diol linker bearing a pyridyl carbamoyl moiety led to in vitro highly potent endothelin receptor antagonists (e.g., 70 and 75). The propargyl derivative 26 significantly reduced blood pressure in in vivo model studies with hypertensive salt-sensitive Dahl rats.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
BosentanEndothelin receptor type BIC 50 (nM)280N/AN/ADetails
BosentanEndothelin-1 receptorIC 50 (nM)40N/AN/ADetails