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, orheteroaryl；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 R39are each hydrogen, alkyl, alkenyl, etc.), CN, heteroaryl,etc.； or(ii) Y and R8 form a 3 to 16 membered unsubstitutedor 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；andW is NH,and formulations thereof, and methods for modulating oraltering the activity of the endothelin family of peptidesand methods for treating endothelin-mediated disorders areprovided.
