Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain.

The present invention provides compounds of Formula (I): ##STR00001##
or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

The present invention provides compounds of Formula (I): ##STR00001##
or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain.

The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R.sup.1 is optionally substituted C.sub.6-24aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R.sup.2 and R.sup.3 are independently hydrogen or C.sub.1-6alkyl group; R.sup.4 and R.sup.5 are independently hydrogen, C.sub.1-6alkyl group optionally substituted with amino, mono- or di(C.sub.1-6alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C.sub.1-6alkyl group or C.sub.1-6 alkoxy group; R.sup.6 is C.sub.1-6alkyl, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkylC.sub.1-6alkyl or arylC.sub.1-6alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins. ##STR00001##

The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R.sup.1 is optionally substituted C.sub.6-24aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R.sup.2 and R.sup.3 are independently hydrogen or C.sub.1-6alkyl group; R.sup.4 and R.sup.5 are independently hydrogen, C.sub.1-6alkyl group optionally substituted with amino, mono- or di(C.sub.1-6alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C.sub.1-6alkyl group or C.sub.1-6 alkoxy group; R.sup.6 is C.sub.1-6alkyl, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkylC.sub.1-6alkyl or arylC.sub.1-6alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins. ##STR00001##

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 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 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.