A class of mono-protected 3-amino-2-hydroxypyridine (MPAHP) ligands that enable the meta-CH arylation of anilines, phenols, phenylacetic acids, and biologically relevant heterocyclic compounds using norbornene as a transient mediator is disclosed. The applicability of this meta-arylation methodology in the pharmaceutical industry is illustrated for heteroaryl substrates and heteroaryl iodide coupling partners, a feat made possible by using the MPAHP ligand. The enabling nature of MPAHP ligands to achieve other meta-CH functionalization processes is also illustrated by the development of a meta-CH amination reaction and a meta-CH alkynylation reaction.

Compounds according to Formula I: ##STR00001##
or a pharmaceutically acceptable salt thereof wherein: A.sub.1 is NR.sub.1 or CR.sub.1, with R.sub.1 being H or methyl, with methyl, if present, optionally being substituted with one or more F; the cyclopropyl moiety can be optionally substituted with one or more methyl and one or more F; A.sub.2-A.sub.5 are N or CR.sub.2-CR.sub.5, respectively, with the proviso that no more than two of the four positions A in A.sub.2-A.sub.5 can be simultaneously N; R.sub.2-R.sub.5 are independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl; R.sub.6 and R.sub.7 are independently H, F, methyl, ethyl, hydroxyl or methoxy or R.sub.2 and R.sub.3 together is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F; R.sub.8 is H or C(1-6)alkyl; R.sub.9 is selected from the group consisting of Formula II, III, IV and V ##STR00002## The compounds can be used as inhibitors of ROR and are useful for the treatment of ROR mediated diseases.

Compounds according to Formula I: ##STR00001##
or a pharmaceutically acceptable salt thereof wherein: A.sub.1 is NR.sub.1 or CR.sub.1, with R.sub.1 being H or methyl, with methyl, if present, optionally being substituted with one or more F; the cyclopropyl moiety can be optionally substituted with one or more methyl and one or more F; A.sub.2-A.sub.5 are N or CR.sub.2-CR.sub.5, respectively, with the proviso that no more than two of the four positions A in A.sub.2-A.sub.5 can be simultaneously N; R.sub.2-R.sub.5 are independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl; R.sub.6 and R.sub.7 are independently H, F, methyl, ethyl, hydroxyl or methoxy or R.sub.2 and R.sub.3 together is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F; R.sub.8 is H or C(1-6)alkyl; R.sub.9 is selected from the group consisting of Formula II, III, IV and V ##STR00002## The compounds can be used as inhibitors of ROR and are useful for the treatment of ROR mediated diseases.

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

The invention relates to new heteroaryl derivatives of the formula wherein X is selected from the group consisting of: N and CH; X is selected from the group consisting of: N and CF; (whith the proviso that at least one of X.sup.1 and X.sup.2 is N), and A is as defined in the description and claims, to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

##STR00001##

The invention relates to new benzonitrile derivatives of the formula (I) wherein R.sup.1 to R.sup.3 and A are as defined in the description and Claims, to their medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

##STR00001##

The present invention relates to a compound represented by Formula (I):

##STR00001##

wherein -L- is C(X), or the like, Z is NR.sup.5, or the like, Z.sup.A is NR.sup.5A, or the like, W is C(R.sup.8R.sup.9)n-, W.sup.A is C(R.sup.3R.sup.4)m-, B is substituted or unsubstituted aromatic carbocyclyl, or the like, Y is a bond, or the like, the ring C is a substituted or unsubstituted aromatic heterocycle, or the like, R.sup.2 is a hydrogen atom, or the like, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising thereof.

The present invention relates to a compound represented by Formula (I):

##STR00001##

wherein -L- is C(X), or the like, Z is NR.sup.5, or the like, Z.sup.A is NR.sup.5A, or the like, W is C(R.sup.8R.sup.9)n-, W.sup.A is C(R.sup.3R.sup.4)m-, B is substituted or unsubstituted aromatic carbocyclyl, or the like, Y is a bond, or the like, the ring C is a substituted or unsubstituted aromatic heterocycle, or the like, R.sup.2 is a hydrogen atom, or the like, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising thereof.

The present invention relates to compounds and methods useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of inflammatory diseases and other diseases involving elevated levels of cytokines and proinflammatory mediators.