Compounds of general formula

##STR00001##

wherein
the wavy bond ˜ is either a double bond or the epoxide,

##STR00002##

or pharmaceutically acceptable salts, solvates, tautomers, or stereoisomers thereof, for use in the treatment of diseases associated with oxidative stress.

Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.

Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.

The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, O, or S; Y1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 2 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y3 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 4 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y5 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); a and P are each present or absent and when present each is a bond.

The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, O, or S; Y1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 2 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y3 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 4 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y5 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); a and P are each present or absent and when present each is a bond.

The invention relates to modulators of Embryonic Ectoderm Development (EED) and/or Polycomb Repressive Complex 2 (PRC2) useful in the treatment of disorders and diseases associated with EEC and PRC2, being macrocyclic azolopyridine derivatives and compositions thereof of Formula I:

##STR00001##

or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, enantiomer, isomer, or tautomer thereof, wherein X.sub.1, X.sub.2, X.sub.3, A.sub.1, A.sub.2, Y, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are as described herein.

The invention relates to novel phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR) and PI3K-related kinase (PIKKs) inhibitor compounds of formula (I), wherein X.sup.1, X.sup.2 and X.sup.3 are N or CH, with the proviso that at least two of X.sup.1, X.sup.2 and X.sup.3 are N; Y is N or CH, These compounds are useful, either alone or in combination with further therapeutic agents, for treating disorders mediated by lipid kinases.

##STR00001##

The invention relates to novel phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR) and PI3K-related kinase (PIKKs) inhibitor compounds of formula (I), wherein X.sup.1, X.sup.2 and X.sup.3 are N or CH, with the proviso that at least two of X.sup.1, X.sup.2 and X.sup.3 are N; Y is N or CH, These compounds are useful, either alone or in combination with further therapeutic agents, for treating disorders mediated by lipid kinases.

##STR00001##

In a preferred embodiment, there is provided a protecting group for protecting the thiol side chain of a cysteine residue, the protecting group comprising a Diels-Alder cycloadduct of a furan and a maleimide, and optionally, a linker interposed between the thiol side chain and the Diels-Alder cycloadduct.

In a preferred embodiment, there is provided a protecting group for protecting the thiol side chain of a cysteine residue, the protecting group comprising a Diels-Alder cycloadduct of a furan and a maleimide, and optionally, a linker interposed between the thiol side chain and the Diels-Alder cycloadduct.