Endothelin Antagonists II

A compound of Formula I

• AA.sup.1 -AA.sup.2 -AA.sup.3 -AA.sup.4 -AA.sup.5 -AA.sup.6 Seq ID No:
• 1
• wherein AA.sup.1 is ##STR78## wherein R is hydrogen, alkyl,
• alkenyl,
• alkynyl,
• cycloalkyl,
• cycloalkylalkyl,
• aryl,
• heteroaryl,
• fluorenylmethyl, ##STR79## wherein R.sup.2 and R.sup.3 are each the same or different and each is hydrogen,
• alkyl,
• alkenyl,
• alkynyl,
• cycloalkyl,
• cycloalkylalkyl,
• aryl,
• arylalkyl,
• heteroaryl, or
• fluorenylmethyl, ##STR80## wherein R.sup.2 is as defined above, --OR.sup.2, wherein R.sup.2 is as defined above, ##STR81## wherein R.sup.2 and R.sup.3 are as defined above, ##STR82## wherein R.sup.9 is F, Cl, Br, or I, --CH.sub.2 --OR.sup.2, wherein R.sup.2 is as defined above, ##STR83## wherein R.sup.2a is hydrogen or alkyl and R.sup.3 is as defined above, ##STR84## wherein R.sup.2a and R.sup.3 are as defined above excluding R.sup.3 is hydrogen, or ##STR85## wherein R.sup.2 is as defined above, R.sup.1 is hydrogen or alkyl,
• Z is
• --O--,
• --S(O).sub.m --, wherein m is zero or an integer of 1 or 2, ##STR86## wherein R.sup.2 is as defined above, --(CH.sub.2).sub.n --, wherein n is zero or an integer of 1, 2, 3, or 4,
• --(CH.sub.2).sub.n --CH.dbd.CH--(CH.sub.2).sub.n' --, wherein n and n' are each independently the same or different and each is as defined above for n, ##STR87## wherein R.sup.1 and R.sup.2 are as defined above, or ##STR88## wherein R.sup.2 and R.sup.3 are each the same or different and each is as defined above,
• X and Y are the same and substituted at the same position on the aromatic ring and each may be 1, 2, 3, or 4 substituents selected from the group consisting of
• hydrogen,
• halogen,
• alkyl,
• --CO.sub.2 R.sup.2, wherein R.sup.2 is as defined above ##STR89## wherein R.sup.2 and R.sup.3 are as defined above, ##STR90## wherein R.sup.2 and R.sup.3 are as defined above, and nitro or ##STR91## wherein R, Z, X, and Y are as defined above;
• AA.sup.2 is ##STR92## wherein R.sup.4 is hydrogen,
• alkyl,
• alkenyl,
• alkynyl,
• cycloalkyl,
• aryl,
• heteroaryl, ##STR93## wherein R.sup.2b and R.sup.3b are each the same or different and each is hydrogen,
• alkyl,
• cycloalkyl,
• aryl, or
• heteroaryl,
• --OR.sup.2b, wherein R.sup.2b is as defined above, ##STR94## wherein R.sup.2b and R.sup.3b are each the same or different and each is as defined above for R.sup.2b and R.sup.3b, ##STR95## wherein R.sup.2b is as defined above, ##STR96## wherein R.sup.2b is as defined above, or ##STR97## wherein R.sup.2b is as defined above, and R.sup.1 and n are as defined above, or AA.sup.2 is absent;
• AA.sup.3 is ##STR98## wherein W is ##STR99## R.sup.5 is hydrogen,
• alkyl,
• aryl,
• heteroaryl, ##STR100## wherein R.sup.2b and R.sup.3b are each the same or different and each is as defined above, ##STR101## wherein R.sup.2b is as defined above, or ##STR102## wherein R.sup.2b is as defined above, and R.sup.1 and n are as defined above, or AA.sup.3 is absent;
• AA.sup.4 and AA.sup.5 are each independently absent or each is independently ##STR103## wherein R.sup.6 is hydrogen, alkyl,
• alkenyl,
• alkynyl,
• cycloalkyl,
• aryl, or
• heteroaryl, and
• R.sup.1 and n are as defined above;
• AA.sup.6 is ##STR104## wherein R.sup.7 is aryl or
• heteroaryl,
• R.sup.8 is ##STR105## wherein R.sup.1 is as defined above, --OR.sup.1, wherein R.sup.1 is as defined above, ##STR106## wherein R.sup.1 is as defined above, or --CH.sub.2 --OR.sup.1, wherein R.sup.1 is as defined above, and
• R.sup.1 and n are as defined above;
• stereochemistry at C* in AA.sup.1, AA.sup.2, AA.sup.3, AA.sup.4, or AA.sup.5 is D, L, or DL and stereochemistry at C* in AA.sup.6 is L;
• or a pharmaceutically acceptable salt thereof.