Discovery of IRL 3461: a novel and potent endothelin antagonist with balanced ET A/ET B affinity

J Sakaki, T Murata, Y Yuumoto, I Nakamura…

Index: Sakaki, Junichi; Murata, Toshiki; Yuumoto, Yoko; Nakamura, Ikushi; Frueh, Thomas; Pitterna, Thomas; Iwasaki, Genji; Oda, Kyoko; Yamamura, Takaki; Hayakawa, Kenji Bioorganic and Medicinal Chemistry Letters, 1998 , vol. 8, # 16 p. 2241 - 2246

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Citation Number: 14

Abstract

IRL 3461, N-butanesulfonyl-[N-(3, 5-dimethylbenzoyl)-N-methyl-3-[4-(5-isoxazolyl)-phenyl]- alanyl]-(L)-valineamide, a potent and bifunctional (ETA+ ETB)[Ki (ETA)= 1.8 nM, Ki (ETB)= 1.2 nM] antagonist was discovered by structural modification of IRL 2500, an ETB selective antagonist. IRL 3461 was found to be stable on incubation with human, rat, mous, and guinea pig plasmas.