The present invention provides compounds that modulate the interaction of TCR with Nck, compositions thereof, and methods of treatment using the same.

Co-crystals comprising the Nuclear receptor related 1 protein-ligand binding domain (Nurr1-LBD) and a cyclopentenone prostaglandin are provided. Also provided are methods of identifying or designing Nurr1-modulating ligands and compounds based on the crystal structures described herein as well as the applications of said ligands and compounds as Nurr1 modulators or medicaments.

The present disclosure relates to a method for preparing a compound of formula (I).

##STR00001##

In the compound of formula (I), n may be 0 to 5 and each of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 may be independently selected from the group consisting of H, —O-Alkyl, halo, alkyl, —CN, or —NO.sub.3.

The present disclosure relates to a method for preparing a compound of formula (I).

##STR00001##

In the compound of formula (I), n may be 0 to 5 and each of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 may be independently selected from the group consisting of H, —O-Alkyl, halo, alkyl, —CN, or —NO.sub.3.

The present invention provides a compound of formula (1) and a pharmaceutical composition comprising the compound useful as a nerve regeneration promoter ##STR00001##
wherein R.sup.1-L- is R.sup.1—OC(O)—, or the like, R.sup.1 is hydrogen atom, optionally-substituted C.sub.1-6 alkyl group, optionally-substituted 3- to 8-membered cycloalkyl group, or the like, R.sup.2 is hydrogen atom or the like, Ring A is formula (2) or formula (3) wherein R.sup.3 is hydrogen atom, optionally-substituted C.sub.1-6 alkyl group, or the like, the part of X, Y, and Z is X═Y—Z, X—Y═Z, or X—Y—Z, X is nitrogen atom, NR.sup.4 (R.sup.4 is hydrogen atom, optionally-substituted C.sub.1-6 alkyl group, or the like), or the like, Y is carbon atom or the like, and Z is carbon atom, nitrogen atom or the like.

The present invention provides a compound of formula (1) and a pharmaceutical composition comprising the compound useful as a nerve regeneration promoter ##STR00001##
wherein R.sup.1-L- is R.sup.1—OC(O)—, or the like, R.sup.1 is hydrogen atom, optionally-substituted C.sub.1-6 alkyl group, optionally-substituted 3- to 8-membered cycloalkyl group, or the like, R.sup.2 is hydrogen atom or the like, Ring A is formula (2) or formula (3) wherein R.sup.3 is hydrogen atom, optionally-substituted C.sub.1-6 alkyl group, or the like, the part of X, Y, and Z is X═Y—Z, X—Y═Z, or X—Y—Z, X is nitrogen atom, NR.sup.4 (R.sup.4 is hydrogen atom, optionally-substituted C.sub.1-6 alkyl group, or the like), or the like, Y is carbon atom or the like, and Z is carbon atom, nitrogen atom or the like.

An object of the present invention is to provide an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like. The α,β-unsaturated amide compound represented by the following formula (I) or a pharmaceutically acceptable salt or the like thereof has anticancer activity and the like: ##STR00001##
[wherein, “A” represents optionally substituted heterocyclic diyl, R.sup.1 represents hydrogen atom or optionally substituted lower alkyl, R.sup.2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents —O—, —S—, —SO.sub.2—, —NR.sup.X1— (wherein, R.sup.X1 represents hydrogen atom or lower alkyl), —CHR.sup.X2— (wherein, R.sup.X2 represents hydrogen atom or hydroxy), —CH═CH—, −CO— or —NH—CO—, and n1 and n2 are the same or different, and each represents 0 or 1].

Co-crystals comprising the Nuclear receptor related 1 protein-ligand binding domain (Nurr1-LBD) and a cyclopentenone prostaglandin are provided. Also provided are methods of identifying or designing Nurr1-modulating ligands and compounds based on the crystal structures described herein as well as the applications of said ligands and compounds as Nurr1 modulators or medicaments.

Compounds that inhibit HIF-2α, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by HIF-2α.

Compounds that inhibit HIF-2α, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by HIF-2α.