Раматробан

Описание

Ramatroban, originally developed for the treatment of cardiovascular pathologies as thromboembolism, was finally introduced in Japan for the treatment of allergic rhinitis. It is a (3R)-enantiomer that can be synthesized in 5 steps from 3-oxo-1,2,3,4- tetrahydrocarbazole by stereoselective reductive amination, using S-phenethylamine as the chiral source, followed by hydrogenolysis, sulfonylation and finally 2-step Ncarboxyethylation. Ramatroban is a potent antagonist of prostaglandin receptors (PGD₂, PGH₂) and thromboxane receptors (TxA₂); accordingly, it blocks the contractions induced by thromboxane or TxA₂-mimetics in animal and human airway smooth muscle. It also prevents, when administered i.v., p.o. or by aerosol, bronchoconstriction induced by PGD₂ or antigen. In animal models of nasal allergy, ramatroban inhibits antigen-induced neutrophil infiltration into nasal mucosa and also inhibits nasal symptoms. In several species including humans, it is well-absorbed, extensively protein-bound (>95%) and eliminated mainly as a glucuro-conjugate; in man, its terminal half-life is 2 to 3 hours.

Химические свойства

WHite to Off-White Solid

Использование

A thromboxane receptor antagonist for use in the treatment of coronary artery disease.

Биологическая активность

Potent dual antagonist of TP/DP 2 (CRTH2) prostanoid receptors (K i values are 4.3, 4.5 and > 10000 nM for hDP 2 , hTP and hDP 1 receptors respectively). Suppresses PGD 2 -induced migration of human eosinophils (IC 50 = 170 nM).