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

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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

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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

Drug	Target	Property	Measurement	pH	Temperature (°C)
Bosentan	Endothelin B receptor	IC 50 (nM)	280	N/A	N/A	Details
Bosentan	Endothelin-1 receptor	IC 50 (nM)	40	N/A	N/A	Details