Cyano containing oxamic acids and derivatives as thyroid receptor ligands

A compound of the Formula

• a prodrug thereof, a geometric or optical isomer thereof, or a pharmaceutically acceptable salt of said compound, said prodrug, or said isomer, wherein:
• R1 and R2 are independently halogen, C1-8 alkyl, —CN or C1-8 perfluoroalkyl;
• provided that at least one of R1 and R2 is —CN;
• R3 is hydrogen or C1-8 alkyl;
• R4 is halogen, C1-8 perfluoroalkyl, C1-8 alkyl, C1-8 alkanoyl, hydroxy-(C1-8 alkyl), aryl optionally substituted with Y and Z, aryl-(C1-8 alkyl), carbocyclic aroyl optionally substituted with Y and Z, C3-10 cycloalkyl optionally substituted with Y and Z, or C3-10 cycloalkyl-(C1-8 alkyl);
• or R4 is the radical
• wherein:
• R9 is hydrogen, C1-8 alkyl, aryl optionally substituted with Y and Z, aryl-(C1-8 alkyl), C3-10 cycloalkyl optionally substituted with Y and Z, or (C3-10 cycloalkyl-(C1-8 alkyl);
• R10 is —OR14;
• R11 is hydrogen or C1-8 alkyl;
• or R10 and R11 may be taken together with the carbon atom to which they are attached to form a carbonyl group;
• R5 is hydroxy, esterified hydroxy or etherified hydroxy;
• R6 is hydrogen, halogen, C1-8 alkyl or C1-8 perfluoroalkyl;
• R7 is hydrogen, C1-8 alkyl or C1-8 perfluoroalkyl;
• R8 is —OR12 or —NR12R13;
• R12 and R13 are each independently hydrogen or C1-8 alkyl;
• R14 is hydrogen, C1-8 alkyl or C1-8 acyl;
• X is O, S(O)a, C═O or NR15;
• a is 0, 1 or 2;
• R15 is hydrogen or C1-8 alkyl;
• Y and Z for each occurrence are independently (a) hydrogen, (b) halogen, (c) trifluoromethyl, (d) —OCF3, (e) —CN, (f) C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OCF3, —CF3 and phenyl, (g) C1-6 alkoxy, (h) aryl optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OCF3, —CF3, C1-4 alkyl and C1-4 alkoxy, (i) —C(O)2R16, (j) —C(O)NR16R17, (k) —C(O)R16, (l) —NR16C(O)NR16R17 or (m) —NR16C(O)R17;
• or Y and Z for any occurrence may be taken together to form (a) a carbocycle of the formula —(CH2)b, or (b) a heterocycle selected from the group consisting of —O(CH2)cO—, (CH2)dNH— and —CH═CHNH—;
• b is 3, 4, 5, 6 or 7;
• c and d are each independently 2, 3, 4, 5 or 6;
• R16 and R17 for each occurrence are independently hydrogen, C1-6 alkyl, C2-6 alkenyl, —(C1-6 alkyl)-C1-6 alkoxy, aryl optionally substituted with Y and Z, het optionally substituted with Y and Z, —(C1-4 alkyl)-aryl optionally substituted with Y and Z, —(C1-4 alkyl)-heterocycle optionally substituted with Y and Z, —(C1-4 alkyl)-hydroxy, —(C1-4 alkyl)-halo, —(C1-4 alkyl)-poly-halo, —(C1-4 alkyl)-CONR18R19 or C3-10 cycloalkyl;
• het for each occurrence is a heterocyclic ring selected from the group consisting of 4-, 5-, 6-, 7- and 8-membered partially and fully saturated, and unsaturated, heterocyclic rings containing from one to four heteroatoms independently selected from the group consisting of N, O and S, and including any bicyclic group in which said heterocyclic ring is fused to a benzene ring or a heterocyclic ring selected from the group consisting of 4-, 5-, 6-, 7- and 8-membered partially and fully saturated, and unsaturated, heterocyclic rings containing from one to four heteroatoms independently selected from the group consisting of N, O and S;
• and
• R18 and R19 for each occurrence are independently hydrogen, C1-6 alkyl, C3-10 cycloalkyl or aryl optionally substituted with Y and Z.