Pharmaceutical composition and method

A compound of the formula

• or a pharmaceutically acceptable salt thereof,
• wherein L is —C(═O)—;
• R1, R2, R4, R5, R6, R7, and R9 are independently H;
• halo (e.g., F, Cl, Br, I);
• C1-3 alkyl;
• C1-3 haloalkyl (e.g., CHF2, CF3);
• or C1-3 alkoxy optionally substituted with 1, 2, 3, or 4 halo (e.g., F, Cl, Br, I), preferably —OCF3, —OCHF2;
• Preferably, R1, R2, R4, R5, R6, R7, and R9 are independently H or halo or methyl;
• R3 is —OCF3;
• R8 is H;
• F, Cl or Br;
• C1-6 alkyl (e.g., preferably methyl, ethyl, propyl, isopropyl, or —C(CH3)3);
• C1-6 haloalkyl (e.g., CHF2, CF3);
• or C2-6 alkoxy optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably ethoxy, propyloxy and isopropyloxy;
• R10 is —CH2COOH;
• and
• R11 is a C1-3 alkyl (e.g., methyl, ethyl, propyl, isopropyl), preferably methyl.

A compound of the formula

• wherein L is —CH2—;
• R1, R2, R4, R5, R6, R7, and R9 are independently H;
• OH;
• halo (e.g., F, Cl, Br, I);
• C1-6 alkyl;
• C1-6 haloalkyl (e.g., CHF2, CF3);
• C1-6 alkoxy optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably —OCF3, —OCHF2;
• R3 is —CF3;
• R8 is H;
• halo (e.g., F, Cl, Br, I);
• C1-6 alkyl (e.g., preferably methyl, ethyl, propyl, isopropyl, or —C(CH3)3);
• C1-6 haloalkyl (e.g., CHF2, CF3);
• or C2-6 alkoxy optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably ethoxy, propyloxy and isopropyloxy;
• Preferably R8 is C1-4 alkyl (e.g., methyl, ethyl, propyl, isopropyl, or —C(CH3)3);
• R10 is —CH2COOH;
• and
• R11 is a C1-3 alkyl (e.g., methyl, ethyl, propyl, isopropyl), preferably methyl.

A compound of the formula

• or a pharmaceutically acceptable salt thereof,
• wherein L is —CH2— or —CH(C1-6 alkyl)-, and preferably —CH2—;
• R1, R2, R4, R5, R6, R7, R9 and R10 are independently H;
• OH;
• halo (e.g., F, Cl, Br, I);
• C1-6 alkyl;
• C1-6 haloalkyl (e.g., CHF2, CF3);
• C1-6 alkoxy optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably —OCF3, —OCHF2;
• or C1-6 alkyl-S— optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably —SCF3;
• R3 is selected from the group consisting of C1-3 haloalkyl (e.g., —CHF2, —CF3), —SCF3, C1-3 alkoxy, or C1-3 haloalkoxy (e.g., —OCF3, —OCHF2), wherein optionally R3 forms a 5 or 6-membered heterocycle with the adjacent R2 or R4 group;
• R8 is H;
• halo (e.g., F, Cl, Br, I);
• C1-6 alkyl;
• C1-6 haloalkyl (e.g., CHF2, CF3);
• C1-6 alkoxy optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably ethoxy, propyloxy and isopropyloxy;
• C1-6 alkyl-S— optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I);
• or —S(O)2—(C1-6 alkyl);
• —NO2;
• R11 is selected from the group consisting of —RL—C(═O)R42, —RL—C(═S)R42, —RL—C(═O)S—R43, —RL—C(═O)N(R52)(R53), —S(O)2—(C1-6 alkyl);
• —RL-phosphono, and —RL-tetrazolyl;
• RL is selected from a bond, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, preferably a bond or C1 alkyl;
• R42 is selected from H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, and C1-6 alkylthiol, wherein R42 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
• R43 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R43 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
• and
• R52 and R53 are independently H, OH(R52 and R53 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, or R52 and R53 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle (e.g., piperidinyl, pyrrolidinyl, and morpholinyl), wherein R52 and R53 each is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl.

A compound of the formula

• or a pharmaceutically acceptable salt thereof,
• wherein L is —CH2—;
• R1, R2, R4, R5, R6, R7, R9 and R10 are independently H;
• OH;
• halo (e.g., F, Cl, Br, I);
• C1-6 alkyl;
• C1-6 haloalkyl (e.g., CHF2, CF3);
• C1-6 alkoxy optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably —OCF3, —OCHF2;
• or C1-6 alkyl-S— optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably —SCF3;
• R3 is selected from the group consisting of —CHF2, —CF3, —OCF3, or —OCHF2;
• R8 is H;
• halo (e.g., F, Cl, Br, I);
• C1-6 alkyl;
• C1-6 haloalkyl (e.g., CHF2, CF3);
• C1-6 alkoxy optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I), preferably ethoxy, propyloxy and isopropyloxy;
• C1-6 alkyl-S— optionally substituted with 1, 2, 3, and 4-6 halo (e.g., F, Cl, Br, I);
• or —S(O)2—C1-6 alkyl);
• —NO2;
• R11 is selected from the group consisting of —RL—COOH;
• and
• RL is selected from a bond, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, preferably a bond.