20-HETE receptor (GPR75) antagonists and methods of use

A compound of formula I or II:

• wherein:
• a) R is OH, C1-C3, F, or H and R3 is OH, C1-C3, F, or H;
• R2 is OH and R3 is C1-C3, F, or H;
• or R3 is OH and R2 is C1-C3, F, or H;
• b) R4 is C1-C3, H, F, or —CH2N3 (azide);
• c) either n is 1 and m is 1 or n is 3 and m is 0;
• either q is 1 and p is 1 or q is 3 and p is 0;
• either m is 0 and p is 1, m is 1 and p is 0, or m is 1 and p is 1;
• and
• either X is O or C and n is 1, or X is C and n is 3;
• and
• d) R1 is CO2R5, wherein R5 is H or a pharmaceutically acceptable salt;
• R1 is NR8R9;
• or R1 is C(O)R6, wherein R6 is OR7;
• R6 is NR8R9;
• R6 is a D-/L-/D,L-α-amino acid (MW<250);
• R6 is —NHS(O)2R10;
• R6 is polyethylene glycol (MW<350);
• R6 is glycerol;
• R6 is glyceride mono- or diester (MW<800);
• or R6 is a carboxylate isostere or mimetic selected from the group consisting of:
• —P(O)(OH)2 or salts thereof
• —S(O)2OH or salts thereof
• wherein ii) a lower alkyl is a C1-C6 alkyl or cycloalkyl;
• ii) R7 is a C1-C6 alkyl or cycloalkyl, or a benzyl;
• iii) R8 is H, a C1-C6 alkyl or cycloalkyl, or a benzyl;
• R9 is H, a C1-C6 alkyl or cycloalkyl, or a benzyl;
• or R8 and R9 together constitute a 3-7 membered ring with the nitrogen;
• and iv) R10 is a phenyl, a C1-C5 alkyl or cycloalkyl, or CF3.