Stereoselective synthesis of a novel and bifunctional endothelin antagonist, IRL 3630

Article abstract of DOI:10.1016/S0960-894X(98)00388-6

IRL 3630 (3), a single enantiomer of IRL 3461 with more potency was identified. Coupling reaction of the racemic fragment (1) with the chiral (L)-valinesulfonamide (2) under a biphasic solvent system (CH₂Cl₂-H₂O) successfully led to the predominant formation of the desired isomer (3) with concomitant isomerization of 1. IRL 3630, N-butanesulfonyl-[N-(3,5- dimethylbenzoyl)-N-methyl-3-[4-(5-isoxazolyl)-phenyl]-(D)-alanyl]-(L)- valineamide, is a highly potent and bifunctional (ET(A)+ET(B)) antagonist [Ki(ET(A))=1.5 nM, Ki(ET(B))=1.2 nM].