Macitentan

CAT#: H205912

CAS#: 441798-33-0

Description: Macitentan (trade name Opsumit) is an endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH). The other two ERAs marketed as of 2014 are bosentan and ambrisentan. Macitentan is a dual ERA, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ETA and ETB. However, macitentan has a 50-fold increased selectivity for the ETA subtype compared to the ETB subtype.

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Synthetic Routes

Macitentan - Synthetic Route 1

Macitentan route01

Synthetic reference

Bolli, Martin H.; Boss, Christoph; Binkert, Christoph; Buchmann, Stephan; Bur, Daniel; Hess, Patrick; Iglarz, Marc; Meyer, Solange; Rein, Josiane; Rey, Markus; Treiber, Alexander; Clozel, Martine; Fischli, Walter; Weller, Thomas. The Discovery of N-​[5-​(4-​Bromophenyl)​-​6-​[2-​[(5-​bromo-​2-​pyrimidinyl)​oxy]​ethoxy]​-​4-​pyrimidinyl]​-​N'-​propylsulfamide (Macitentan)​, an Orally Active, Potent Dual Endothelin Receptor Antagonist. Journal of Medicinal Chemistry. Volume 55. Issue 17. Pages 7849-7861. Journal; Online Computer File. (2012).

Macitentan - Synthetic Route 2

Macitentan route02

Synthetic reference

Anon. Process for preparing N-​[5-​(4-​bromophenyl)​-​6-​[2-​[(5-​bromo-​2-​pyrimidinyl)​oxy]​ethoxy]​-​4-​pyrimidinyl]​-​N'-​propylsulfamide and intermediates thereof. IP.com Journal. Volume 14. Issue 2A. Pages 1-11. Journal; Patent. (2014).

Macitentan - Synthetic Route 3

Macitentan route03

Synthetic reference

Reddy, Srinivas Reddy Desi; Rane, Dnyandev Ragho; Velivela, Srinivas Rao; Pendem, Krishnaiah. A novel process for the preparation macitentan. Assignee Optimus Drugs (P) Ltd., India. IN 2014CH03334. (2016).

Macitentan - Synthetic Route 4

Macitentan route04

Synthetic reference

Abele, Stefan; Funel, Jacques-Alexis; Schindelholz, Ivan. Preparation of pyrimidine intermediates useful for the manufacture of macitentan. Assignee Actelion Pharmaceuticals Ltd., Switz. WO 2014155304. (2014).