The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II):

##STR00001##

comprising treating a compound of Formula (I):

##STR00002##

with a transition metal catalyst and under alkylation conditions as valence and stability permit.

The invention relates to novel heteroarylamide derivatives having formula (I) and N-oxides, stereoisomers and pharmaceutically acceptable salts thereof, where R.sub.A, R.sub.B, R1 1, R, R, z and X are as defined in the claims. The arylamide derivatives of formula (I) have antiandrogenic properties. The invention also relates to compounds of formula (I) for use as a medicament and to pharmaceutical compositions comprising them and to their preparation. ##STR00001##

The present invention provides a novel and improved process for the production of the production of hindered anilines containing perfluoroalky groups in good yield any by using close to stoichiometric amounts of acylating agent.

Compounds having the following structure (VI-A): ##STR00001##
or any pharmaceutically acceptable salt or solvate thereof, or any stereoisomer thereof, wherein R.sub.E1, R.sub.E2, R.sub.E3, R.sub.E4, Z.sub.E2 and Z.sub.E3 are as disclosed herein, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating disorders associated with necrosptosis are also provided.

Compounds having the following structure (VI-A): ##STR00001##
or any pharmaceutically acceptable salt or solvate thereof, or any stereoisomer thereof, wherein R.sub.E1, R.sub.E2, R.sub.E3, R.sub.E4, Z.sub.E2 and Z.sub.E3 are as disclosed herein, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating disorders associated with necrosptosis are also provided.

The invention provides topical compositions and methods for using the compositions. The compositions can be used for the treatment of fibrotic or connective tissue disorders involving scarring, sub-dermal plaque accumulations, or fibrosis of muscle tissue. The disorders can be painlessly treated by the topical application of a composition described herein. One or more calcium channel blocker agents can serve as an active ingredient of the compositions, optionally in combination with, for example, one or more of emu oil and superoxide dismutase. The composition can further include pharmaceutically acceptable carriers that can facilitate the non-invasive transdermal delivery of the active(s) to subdermal sites.

The invention provides topical compositions and methods for using the compositions. The compositions can be used for the treatment of fibrotic or connective tissue disorders involving scarring, sub-dermal plaque accumulations, or fibrosis of muscle tissue. The disorders can be painlessly treated by the topical application of a composition described herein. One or more calcium channel blocker agents can serve as an active ingredient of the compositions, optionally in combination with, for example, one or more of emu oil and superoxide dismutase. The composition can further include pharmaceutically acceptable carriers that can facilitate the non-invasive transdermal delivery of the active(s) to subdermal sites.

The invention relates to compound shown with formula (I) for a pharmaceutically acceptable derivative thereof for use as a novel inhibitor of BCL-2. ##STR00001##

The invention relates to compound shown with formula (I) for a pharmaceutically acceptable derivative thereof for use as a novel inhibitor of BCL-2. ##STR00001##

The invention provides topical compositions and methods for using the compositions. The compositions can be used for the treatment of fibrotic or connective tissue disorders involving scarring, sub-dermal plaque accumulations, or fibrosis of muscle tissue. The disorders can be painlessly treated by the topical application of a composition described herein. One or more calcium channel blocker agents can serve as an active ingredient of the compositions, optionally in combination with, for example, one or more of emu oil and superoxide dismutase. The composition can further include pharmaceutically acceptable carriers that can facilitate the non-invasive transdermal delivery of the active(s) to subdermal sites.