Sulfonamides and derivatives thereof that modulate the...

C - Chemistry – Metallurgy – 07 – D

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C07D 413/12 (2006.01) A61K 31/42 (2006.01) A61P 9/08 (2006.01) C07D 261/16 (2006.01) C07D 413/14 (2006.01)

Patent

CA 2395684

A compound that has formula IV: (see formula IVa) (see formula IVb) (see formula IVc) or (see formula IVd) or pharmaceutically acceptable derivatives thereof, wherein: X is S or -C(R3) =C(R4) -; R1 is halo or lower alkyl; R2 is lower alkyl; R3 and R4 are hydrogen, halo, cyano, etc.; R5 is lower alkyl or -(CH2) x C(O)(CH2)y CH3; R6 is lower alkyl, -(CH2) x C(O)(CH2)y CH3, or heteroaryl; R7 is hydrogen, hydroxy, alkoxy, etc.; x and y are each independently 0 to 14; Y and R8 are: (i) Y is O; and R8 is CONR38R39 (where R38 and R39 are each hydrogen, alkyl, alkenyl, etc.), CN, heteroaryl, etc.; or (ii) Y and R8 form a 3 to 16 membered unsubstituted or substituted cyclic or heterocyclic ring; R9 is H; a is 1 if Y2 is carbon; a is 0 if Y2 is nitrogen; b is 1 if Y1 is carbon; b is 0 if Y1 is nitrogen; and W is NH, and formulations thereof, and methods for modulating or altering the activity of the endothelin family of peptides and methods for treating endothelin-mediated disorders are provided.

Cette invention a trait à des thiényl-, furyl-, pyrrolyl- et phénylsulfonamides, à des formulations de dérivés admissibles du point de vue pharmaceutique de ces substances ainsi qu'à des techniques visant à moduler ou à modifier l'activité de peptides de la famille de l'endothéline. Elle porte notamment sur des N-(isoxazolyl)thiénylsulfonamides, des N-(isoxazolyl)furylsulfonamides et des N-(isoxazolyl)pyrrolylsulfonamides, des formulations de ceux-ci et des procédés dans lesquels ces sulfonamides sont utilisés pour l'inhibition de la liaison d'un peptide d'endothéline à un récepteur de l'endothéline et ce, par la mise en contact du récepteur avec le sulfonamide. Elle se rapporte encore à des procédés de traitement de troubles dont l'endothéline est à l'origine, lesquels procédés consistent à administrer des doses efficaces d'un ou de plusieurs de ces sulfonamides ou de promédicaments de ces derniers, inhibant l'activité de l'endothéline.

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