Biphenyl amide lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1

A compound structurally represented by the formula:

• wherein:
• R1 is
• wherein the dashed line represents the point of attachment to the R1 position;
• R2 is
• —H, -halogen, —CH3 (optionally substituted with 1 to 3 halogens), or
• —O—CH3 (optionally substituted with 1 to 3 halogens);
• R3 is
• -halogen, —CH3 (optionally substituted with 1 to 3 halogens), or —O—CH3 (optionally substituted with 1 to 3 halogens);
• R4 is —H or -halogen;
• R5 is
• wherein the dashed line represents the point of attachment to the R5 position;
• wherein n is 0, 1, or 2, and wherein when n is 0, then “(CH2) n” is a bond;
• wherein m is 1 or 2;
• R6 is
• —H, —(C1-C3)alkyl(optionally substituted with 1 to 3 halogens),
• —(C1-C3)alkyl-O—R20—(C1-C3)alkyl-pyrrolidinyl, phenyl, —HET1,
• -HET2, —CH2-phenyl, —CH2—HET1, —CH2—HET,
• —(C1-C3)alkyl-N(R20)(R20), —(C1-C3)alkyl-N(O—)(CH3)2,
• —(C1-C3)alkyl-C(O)N(R41)(R41), —CH(C(O)OH)(CH2OR20),
• —CH(C(O)OH)(CH2N(R20)(R20)), —(C1-C3)alkyl-C(O)O—R20,
• wherein the dashed line indicates the point of attachment to the position indicated by R6;
• HET1 is
• wherein the dashed line indicates the point of attachment to the position indicated by HET1;
• HET2 is
• wherein the dashed line indicates the point of attachment to the position indicated by HET2;
• R7 is
• —H, —(C1-C3)alkyl(optionally substituted with 1 to 3 halogens), or
• —(C1-C3)alkyl-O—R20
• R8 is
• —H, —OH, —(C1-C6)alkyl(optionally substituted with 1 to 3 halogens),
• —(C1-C3)alkyl-O—R20, —C(O)—(C1-C4)alkyl(optionally substituted with 1 to 3 halogens), —C(O)O—(C1-C4)alkyl(optionally substituted with 1 to 3 halogens), or
• —C(O)—N(R20)(R20);
• R9 is
• —H, -halogen, —CH3 (optionally substituted with 1 to 3 halogens), or
• —O—CH3 (optionally substituted with 1 to 3 halogens);
• R10 is independently at each occurrence —H, or -halogen;
• R11 is independently at each occurrence —H, —CH3 or —CH2—CH3;
• R20 is independently at each occurrence —H, or —(C1-C4)alkyl(optionally substituted with 1 to 3 halogens);
• R21 is independently at each occurrence —H, -halogen, or —(C1-C4)alkyl(optionally substituted with 1 to 3 halogens);
• R22 is independently at each occurrence —H, or —(C1-C6)alkyl(optionally substituted with 1 to 3 halogens);
• R23 is independently at each occurrence —H, —(C1-C4)alkyl, or —C(O)O—(C1-C4)alkyl;
• R24 is independently at each occurrence —H, -halogen, or —(C1-C6)alkyl(optionally substituted with 1 to 3 halogens);
• R31 is independently at each occurrence —H, -halogen, or —(C1-C6)alkyl(optionally substituted with 1 to 3 halogens);
• and
• R41 is independently at each occurrence —H, or —(C1-C6)alkyl(optionally substituted with 1 to 3 halogens);
• provided the compound is not {[3′-Chloro-4′-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carbonyl]-amino}-acetic acid, 4-{[3′-Chloro-4′-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carbonyl]-amino}-butyric acid, 3′-Chloro-4′-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carboxylic acid piperidin-4-ylamide,
• or 3-[3-Chloro-4′-(4-methyl-piperazine-1-carbonyl)-biphenyl-4-ylmethyl]-1-cyclohexyl-pyrrolidin-2-one;
• or a pharmaceutically acceptable salt thereof.