The application relates to a compound of Formula (I′) or (I):

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or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of thyroid hormone receptors, a pharmaceutical composition comprising a compound of Formula (I′) or (I), and a method of treating or preventing a disease or disorder regulated by thyroid hormone.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R.sub.1 is alkyl, Cl, F or Br; R.sub.2 is H or F; R.sub.3 is selected from H and alkyl; R.sub.4 is selected from H and C(O)R.sub.6; R.sub.5 is H; or R.sub.4 and R.sub.5 are linked to form a heterocyclic group which is optionally substituted with one or more R.sub.10 groups; R.sub.6 is selected from R.sub.7, OR.sub.7 and NR.sub.8R.sub.9; R.sub.7, R.sub.8 and R.sub.9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R.sub.10 groups; each R.sub.10 is independently selected from halogen, OH, CN, NO.sub.2, COO-alkyl, aralkyl, SO.sub.2-alkyl, SO.sub.2-aryl, COOH, CO-alkyl, CO-aryl, NH.sub.2, NH-alkyl, N(alkyl).sub.2, CF.sub.3, alkyl and alkoxy; X and Z are each independently CR.sub.11, and Y is selected from CR.sub.11 and N; and R.sub.11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R.sub.1 is alkyl, Cl, F or Br; R.sub.2 is H or F; R.sub.3 is selected from H and alkyl; R.sub.4 is selected from H and C(O)R.sub.6; R.sub.5 is H; or R.sub.4 and R.sub.5 are linked to form a heterocyclic group which is optionally substituted with one or more R.sub.10 groups; R.sub.6 is selected from R.sub.7, OR.sub.7 and NR.sub.8R.sub.9; R.sub.7, R.sub.8 and R.sub.9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R.sub.10 groups; each R.sub.10 is independently selected from halogen, OH, CN, NO.sub.2, COO-alkyl, aralkyl, SO.sub.2-alkyl, SO.sub.2-aryl, COOH, CO-alkyl, CO-aryl, NH.sub.2, NH-alkyl, N(alkyl).sub.2, CF.sub.3, alkyl and alkoxy; X and Z are each independently CR.sub.11, and Y is selected from CR.sub.11 and N; and R.sub.11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.