Endotherlin antagonists

A compound of Formula I

• AA.sup.1 -AA.sup.2 -AA.sup.3 -AA.sup.4 -AA.sup.5 -AA.sup.6
• wherein AA.sup.1 is ##STR108## wherein R is
• hydrogen,
• alkyl, ##STR109## wherein R.sup.3 and R.sup.4 are each the same or different and each is hydrogen,
• alkyl,
• alkenyl,
• alkynyl,
• cycloalkyl,
• cycloalkylalkyl,
• aryl,
• heteroaryl, or
• fluorenylmethyl, ##STR110## wherein R.sup.3 and R.sup.4 are each the same or different and each is as defined above, ##STR111## wherein R.sup.3 and R.sup.4 are each the same or different and each is as defined above, ##STR112## wherein R.sup.3 and R.sup.4 are defined above or ##STR113## wherein R.sup.3' is F, Cl, Br, or I, and R.sup.3 is as defined above, R.sup.2 is hydrogen or methyl,
• R.sup.2', R.sup.2" and R.sup.2'" are each the same or different and each is
• hydrogen,
• alkyl,
• aryl, or
• heteroaryl with the proviso that at least one of R.sup.2, R.sup.2', and R.sup.2" is aryl or heteroaryl and R.sup.2'" is hydrogen or methyl,
• n i s zero, and
• n' is zero or an integer of 1, 2, or 3;
• AA.sup.2 is
• Apa,
• Ahp,
• Dip,
• D-Phe,
• Phe,
• HomoArg,
• Arg, or ##STR114## wherein R.sup.11 is hydrogen or methyl,
• n is zero,
• R.sup.10 is hydrogen or methyl,
• n' is zero or an integer of 1, 2, 3, 4, or 5, and
• R.sup.10' is alkyl,
• OH, ##STR115## wherein R.sup.3" and R.sup.4' are each the same or different and each is hydrogen,
• alkyl, or
• aryl, ##STR116## wherein R.sup.3" and R.sup.4' are as defined above, ##STR117## wherein R.sup.4' is as defined above;
• --S(O).sub.m R.sup.3" wherein m is zero or an integer of 1 of 2 and R.sup.3" is as defined above except that R.sup.3" is not hydrogen;
• AA.sup.3 is
• Lys,
• Tyr,
• Phe, or ##STR118## wherein R.sup.11 is hydrogen or methyl,
• n is zero,
• R.sup.10 is hydrogen or methyl,
• n" is zero or an integer of 1, 2, or 3, and
• R.sup.10' is
• alkyl,
• aryl, ##STR119## wherein R.sup.3" and R.sup.4' are as defined above;
• ##STR120## wherein R.sup.4' is as defined above;
• AA.sup.4 and AA.sup.5 are each
• Phe,
• Lys,
• Glu,
• Pro, or ##STR121## wherein R.sup.11 is hydrogen or methyl,
• n is zero,
• R.sup.10 is hydrogen or methyl,
• n' is zero, and
• R.sup.10' is alkyl, or cycloalkyl, or
• one of AA.sup.2 or AA.sup.4 is absent;
• AA.sup.6 is ##STR122## wherein R.sup.11 is hydrogen or methyl,
• n is zero,
• R.sup.12 is hydrogen, or methyl,
• n' is zero or an integer of 1, 2, or 3,
• R.sup.12' is aryl or heteroaryl,
• R.sup.13 is
• --(CH.sub.2).sub.n --CO.sub.2 H wherein n is zero or an integer of 1, 2, 3, 4, 5, or 6,
• --(CH.sub.2).sub.n --OH wherein n is zero or an integer of 1, 2, 3, 4, 5, or 6, or ##STR123## wherein n, R.sup.3, R.sup.4 are defined above, ##STR124## wherein R.sup.14 is hydrogen or
• --CH.sub.2 CO.sub.2 H,
• stereochemistry at C* in AA.sup.1 is D,
• stereochemistry at C* in AA.sup.2, AA.sup.3, AA.sup.4 or AA.sup.5 is D or L
• and stereochemistry at C* in AA.sup.6 is L;
• with the exclusion of compounds wherein AA.sup.1 is ##STR125## wherein C*H is D or L stereochemistry, or ##STR126## wherein C*H is D or L stereochemistry, AA.sup.2 is ##STR127## wherein C*H is D or L stereochemistry, AA.sup.3 is ##STR128## wherein C*H is D or L stereochemistry, AA.sup.4 and AA.sup.5 are each ##STR129## wherein C*H is D or L stereochemistry, and AA.sup.6 is ##STR130## wherein C*H is D or L stereochemistry but wherein only one of AA.sup.1 or AA.sup.2 or AA.sup.3 or AA.sup.4 or AA.sup.5 or AA.sup.6 are of D-stereochemistry;
• or a pharmaceutically acceptable salt thereof.