Thyroid receptor ligands

A compound of Formula (I)

• 15
• the stereoisomers and prodrugs thereof, and the pharmaceutically acceptable salts of said compounds, stereoisomers, and prodrugs, wherein:
• W is oxygen, sulfur, —SO—, —S(O)2, —CH2—, —CF2—, —CHF—, —C(O)—, —CH(OH)—, —NRa, or —C(═CH2)—;
• R1, R2, R3, and R6 are each independently hydrogen, halogen, —(C1-C10)alkyl, —CF3, —OCF3, —O(C1-C8)alkyl, or —CN;
• R4 is hydrogen, —(C1-C12)alkyl substituted with zero to three substituents independently selected from Group V, —(C2-C12)alkenyl, —(C2-C12)alkynyl, halogen, —CN, —ORb, —SRc, —S(O)Rc, —S(O)2Rc, aryl, heteroaryl, —(C3-C10)cycloalkyl, heterocycloalkyl, —S(O)2NRcRd, —C(O)NRcRd, —C(O)ORc, —NRaC(O)Rd, NRaC(O)NRcRd, —NRaS(O)2Rd, or —C(O)Rc;
• or
• R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula —(CH2)i— or a heterocyclic ring of formula —(CH2)k-Q-(CH2)l— wherein Q is oxygen, sulfur, or —NRe—;
• i is 3, 4, 5, or 6;
• k is 0, 1, 2, 3, 4, or 5;
• and l is 0, 1, 2, 3, 4, or 5;
• and wherein said carbocyclic ring and said heterocyclic ring are each substituted with zero to four substituents independently selected from —(C1-C4)alkyl, —ORb, oxo, —CN, phenyl, or —
• R5 is hydroxy, —O(C1-C6)alkyl, —OC(O)Rf, fluorine, or —C(O)ORc;
• or
• R4 and R5 are taken together along with the carbon atoms to which they are attached to form a heterocyclic ring selected from the group consisting of —CRc═CRa—NH—, N═CRa—NH, —CRc═CRa—O—, —CRc═CRa—S—, —CRc═N—NH—, and —CRa═CRa—CRa═N—;
• Ra for each occurence is independently hydrogen, or —(C1-C6)alkyl substituted with zero or one —(C3-C6)cycloalkyl or methoxy;
• Rb for each occurence is independently hydrogen, —(C1-C12)alkyl substituted with zero to three substituents independently selected from Group V, aryl, heteroaryl, —(C3-C10)cycloalkyl, heterocycloalkyl, —C(O)NRcRd, or —C(O)Rf;
• Rc and Rd for each occurence are each independently hydrogen, —(C1-C12)alkyl substituted with zero to three substituents independently selected from Group VI, —(C2-C12)alkenyl, —(C2-C12)alkynyl, aryl, heteroaryl, —(C3-C10)cycloalkyl, or heterocycloalkyl;
• provided that when R4 is the moiety —SRc, —S(O)Rc, or —S(O)2Rc, Rc is other than hydrogen;
• or
• Rc and Rd are taken together along with the atom(s) to which they are attached to form a 3-10 membered heterocylic ring which may optionally contain a second heterogroup selected from oxygen, —NRe—, or sulfur;
• and wherein said heterocyclic ring is substituted with zero to four substituents independently selected from —(C1-C4)alkyl, —ORb, oxo, —CN, phenyl, or —NRaRg;
• Re for each occurence is hydrogen, —CN, —(C1-C10)alkyl substituted with zero to three substituents independently selected from Group V, —(C2-C10)alkenyl, —(C2-C10)alkoxy, —(C3-C10)cycloalkyl, aryl, heteroaryl, —C(O)Rf, —C(O)ORf, —C(O)NRaRf, or —S(O)2Rf;
• Rf for each occurence is independently —(C1-C10)alkyl substituted with zero to three substituents independently selected from Group VI, —(C2-C12)alkenyl, —(C2-C10)alkynyl, —(C3-C10)cycloalkyl, aryl, heteroaryl, or heterocycloalkyl;
• Rg for each occurence is independently hydrogen, —(C1-C6)alkyl, —(C2-C6)alkenyl, aryl, —C(O)Rf, —C(O)ORf, —C(O)NRaRf, —S(O)2Rf, or —(C3-C8)cycloalkyl;
• Group V is halogen, —CF3, —OCF3, —OH, oxo, —(C1-C6)alkoxy, —CN, aryl, heteroaryl, —(C3-C10)cycloalkyl, heterocycloalkyl, —SRf, —S(O)Rf, —S(O)2Rf, —S(O)2NRaRf,
• NRaRg, or —C(O)NRaRf;
• Group VI is halogen, hydroxy, oxo, —(C1-C6)alkoxy, aryl, heteroaryl, —(C3-C8)cycloalkyl, heterocycloalkyl, —CN, or —OCF3;
• provided that when R4 is —(C1-C12)alkyl substituted with zero to three substituents independently selected from Group V, wherein said Group V substituent is oxo, said oxo group is substituted on a carbon atom other than the C1 carbon atom in —(C1-C12)alkyl;
• aryl for each occurence is independently phenyl or naphthyl substituted with zero to four substituents independently selected from halogen, —(C1-C6)alkyl, —CN, —SRf, —S(O)Rf, —S(O)2Rf, —(C3-C6)cycloalkyl, —S(O)2NRaRf, —NRaRf, —C(O)NRaRf, —ORb, —perfluoro-(C1-C4)alkyl, or —COORf;
• provided that when said substituent(s) on aryl are —SRf, —S(O)Rf, —S(O)2Rf, —S(O)2NRaRf, —NRaRf, —C(O)NRaRf, —ORb, or —COORf, said substituents Rb, Rf, and Rg, are other than aryl or heteroaryl;
• heteroaryl for each occurence is independently a 5-, 6-, 7-, 8-, or 9-membered monocyclic or bicyclic ring having from one to three heteroatoms selected from O, N, or S;
• wherein in said bicyclic ring, a monocyclic heteroaryl ring is fused to a benzene ring or to another heteroaryl ring, and having zero to three substituents independently selected from halogen, —(C1-C4)alkyl, —CF3, —ORb, —NRaRg, or —COORf;
• provided that when said substituent(s) on heteroaryl are —NRaRg, —ORb, or —COORf, said substituents Rb, Rf, and Rg, are other than aryl or heteroaryl;
• heterocycloalkyl for each occurence is independently a 5-, 6-, 7-, 8-, or 9-membered monocyclic or bicyclic cycloalkyl ring having from one to three heteroatoms selected from oxygen, —NRe, or sulfur, and having zero to four substituents independently selected from —(C1-C4)alkyl, —ORb, oxo, —CN, phenyl, or —NRaRg;
• and
• X is
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