Cyclic 11-beta hydroxysteroid dehydrogenase type 1 inhibitors

A compound of formula (I)

• enantiomers, diastereomers, solvates, or salts thereof wherein:
• A is a 5- to 20-membered non-aromatic bi-, tri- or polycyclic ring system optionally containing 1-3 heteroatoms selected from N, O, S, S(O) and S(O)2, which may be optionally substituted with one or more R4's;
• X is —C(═O)OH, —C(═O)C(═O)OH, —C(═O)NR9R9, tetrazolyl, or —C(═O)NHS(O)2R9;
• W is absent, (—CR8aR8b—)m, (—CR8aR8b—)m—O—, (—CR8aR8b—)m—N(R14)—, C3-6 cycloalkyl, alkenyl or alkynyl, wherein the cycloalkyl or alkenyl may be optionally substituted with one or more R8a'S;
• M is 1-3;
• Z is C3-10 alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, all of which may be optionally substituted with one or more R4's, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;
• provided that W and Z, or when W is absent, X and Z, are attached to the same carbon on Ring A;
• R4, at each occurrence, is independently selected from hydrogen, alkyl, aryl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, F, I, Br, ═O, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR10, —OR10, —OH, —OCF3, —SH, —SR10, —C(═O)NR9R9, —NR9R9, —S(O)2NR9R9, —NR9S(O)2CF3, —C(═O)NR9S(O)2R9, —S(O)2NR9C(═O)OR9, —S(O)2NR9C(═O)NR9R9, —C(═O)NR9S(O)2CF3, —C(═O)R10, —NR9C(═O)R10, —OC(═O)R10, —S(═O)R10, —S(O)2R10, —O—S(O)2R10, —NR9C(═O)OR8 or —NR9S(O2)R8, wherein the alkyl, aryl, alkenyl, alkynyl, cycloalkyl, or heterocyclyl may be optionally substituted with one or more R5's;
• R5, at each occurrence, is independently selected from hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR10, —OCF3, —OR10, —OH, —SH, —SR10, —C(═O)NR9R9, —NR9R9, —S(O)2NR9R9, —NR9S(O)2CF3, —C(═O)NR9S(O)2R9, —S(O)2NR9C(═O)OR9, —S(O)2NR9C(═O)NR9R9, —C(═O)NR9S(O)2CF3, —C(═O)R10, —NR9C(═O)R10, —OC(═O)R10, —S(═O)R10, —S(O)2R10, —O—S(O)2R10, —NR9C(═O)OR8 or —NR9S(O2)R8;
• R8, at each occurrence, is independently alkyl, aryl or heterocyclyl;
• R8a, at each occurrence, is independently hydrogen, alkyl or aryl;
• R8b, at each occurrence, is independently hydrogen, —C(═O)OH, alkyl, —OH, halo, —CN, —OR10, —C(═O)R10 or —C(═O)NR9R9, wherein the alkyl may be optionally substituted with one or more R9a's;
• or
• R8a and R8b are taken together with the carbon to which both are attached to form a 3- to 7-membered ring, which may optionally contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with 0-3 R9a;
• R9, at each occurrence, is independently alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R9a, and the heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;
• or
• two R9's together with the nitrogen to which they are attached form a unsaturated, saturated or partially saturated cyclic ring system containing from 2-10 carbon atoms and from 0-4 additional heteroatoms selected from N, O, S, S(O) and S(O)2, wherein said ring system may be optionally substituted or fused with one or more R9a's;
• R9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, halo, ═O, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR14, —OCF3, —OR10, —OH, —OCF3, —SH, —SR14, —C(═O)NR14R14, —NR14R14, —S(O)2NR14R14, —NR14S(O)2CF3, —C(═O)NR14S(O)2R10, —S(O)2NR14C(═O)OR10, —S(O)2NR14C(═O)NR14R14, —C(═O)NR14S(O)2R14, —C(═O)R14, —NR14C(═O)R14, —OC(═O)R14, —C(═NR14)NR14R14, —NHC(═NR14)NR14R14, —S(═O)R14, —S(O)2R14, —OS(O)2R14, —NR14C(═O)OR10, —NR14S(O2)R8, —C(═O)R10, —OC(═O)NR14R14, —NR14C(═O)NR14R14 or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl may be optionally substituted with 0-3 R10a;
• R10, at each occurrence, is independently selected from alkyl, cycloalkyl, alkenyl, alkynyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;
• R10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR14, —OCF3, —OR14, —OH, —SH, —SR14, —C(═O)NR14R14, —NR14R14, —S(O)2NR14R14, —NR14S(O)2CF3, —C(═O)NR14S(O)2R14, —S(O)2NR14C(═O)OR14, —S(O)2NR14C(═O)NR14R14, —C(═O)NR14S(O)2CF3, —C(═O)R14, —NR14C(═O)R14, —OC(═O)R14, —C(═NR14)NR14R14, —NHC(═NR14)NR14R14, —S(═O)R14, —S(O)2R14, —NR14C(═O)OR8, —NR14S(O2)R8 or arylalkyl;
• R14, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl, aryl or arylalkyl, wherein the alkyl, cycloalkyl, aryl or arylalkyl may be optionally substituted with 0-3 R14a;
• R14a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR15, —OCF3, —OR15, —OH, —SH, —SR15, —C(═O)NR15R15, —NR15R15, —S(O)2NR15R15, —NR15S(O)2CF3, —C(═O)NR15S(O)2R15, —S(O)2NR15C(═O)OR15, —S(O)2NR15C(═O)NR15R15, —C(═O)NR15S(O)2CF3, —C(═O)R15, —NR15C(═O)R15, —OC(═O)R15, —C(═NR15)NR15R15, —NHC(═NR15)NR15R15, —S(═O)R15, —S(O)2R15, —NR15C(═O)OR8, —NR15S(O2)R8 or arylalkyl;
• R15, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl, aryl or arylalkyl;
• and
• provided that:
• (i) when W is absent, Z is phenyl, X is —C(═O)OH, lower alkyl or tetrazolyl, A is not bicyclo(2,2,1)heptanyl, bicyclo(2,2,1)heptenyl, bicyclo(2,2,2)octanyl, or bicyclo(2,2,2)octenyl;
• (ii) when W is absent, Z is optionally substituted phenyl, or heterocyclyl, X is —C(═O)OH or —C(═O)NR9R9 and R9 is lower alkyl, A is not 8-azabicyclo(3.2.1)octanyl;
• (iii) the compound is not a compound of the following structure:
• wherein R is optionally substituted phenyl;
• (iv) the compound is not a compound of the following structure:
• (v) the compound is not a compound of the following structure:
• (vi) the compound is not a compound of the following structure:
• and
• (vii) when Z is optionally substituted C3-10 alkyl, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted arylalkyl, A is not
• which is substituted with at least one R4 other than hydrogen;
• or
• which may be optionally substituted with one or more R4's.