Processes for preparing 3-substituted phenylalkylamines comprising reacting a phenyl boronic compound with an ?-? unsaturated carbonyl-containing compound via an asymmetric 1,4-addition reaction, followed by reductive alkylation. The processes may be useful in the synthesis of tapentadol.

Processes for preparing 3-substituted phenylalkylamines comprising reacting a phenyl boronic compound with an ?-? unsaturated carbonyl-containing compound via an asymmetric 1,4-addition reaction, followed by reductive alkylation. The processes may be useful in the synthesis of tapentadol.

A once daily controlled release pharmaceutical compositions comprising tapentadol, wherein preferably the mean T.sub.max of tapentadol is reached after 10 hours of administration of the composition. The composition comprises tapentadol, such that it maintains serum concentration of tapentadol of at least about 20 ng/ml for at least about 17 hours after oral administration of the composition. According to one embodiment the controlled release pharmaceutical composition comprises tapentadol, which is gastroretentive.

A hitherto unknown crystalline form of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence.

A hitherto unknown crystalline form of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence.

The present invention relates to a process for the preparation of tapentadol and analogs or compounds or stereoisomers of formula (I), Formula I wherein, A is aryl, heteroaryl, and cycloalkyl; R is H, OH, OR.sup.1, halogen, C.sub.1-C.sub.12 alkyl, cycloalkyl, aryl or heteroaryl; R.sup.1 is C.sub.1-C.sub.12 alkyl, cycloalkyl, aryl or heteroaryl, wherein each of these groups may further be substituted with one or more substituent selected from H, OH, halogen, CN, NO.sub.2, C.sub.1-C.sub.4 alkyl or phenyl. Further, the multi-step process involves no column chromatography purification until the very last step. This makes this process highly commercially viable and industrially useful. ##STR00001##

The present invention relates to a process for the preparation of tapentadol and analogs or compounds or stereoisomers of formula (I), Formula I wherein, A is aryl, heteroaryl, and cycloalkyl; R is H, OH, OR.sup.1, halogen, C.sub.1-C.sub.12 alkyl, cycloalkyl, aryl or heteroaryl; R.sup.1 is C.sub.1-C.sub.12 alkyl, cycloalkyl, aryl or heteroaryl, wherein each of these groups may further be substituted with one or more substituent selected from H, OH, halogen, CN, NO.sub.2, C.sub.1-C.sub.4 alkyl or phenyl. Further, the multi-step process involves no column chromatography purification until the very last step. This makes this process highly commercially viable and industrially useful. ##STR00001##

The present invention provides a method of inhibiting, suppressing or preventing levodopa-induced dyskinesia in a patient suffering from Parkinson's Disease, comprising the step of administering to the patient a pharmaceutical composition comprising at least one compound of the invention. The present invention further provides a method of inhibiting, suppressing or preventing Parkinson's Disease in a patient, comprising the step of administering to the patient a pharmaceutical composition comprising at least one compound of the invention.

This invention relates to novel diarylamino compounds that bind to the sigma-2 receptor, to pharmaceutical compositions comprising such compounds, and to methods for inhibiting or restoring synapse loss in neuronal cells, modulating a membrane trafficking change in neuronal cells, and treating cognitive decline and neurodegenerative diseases and disorders therewith.

The present disclosure relates to Tapentadol Hydrochloride in the polymorphic crystalline Form B, which is substantially free of polymorphic Form A as well as essentially free of low alkyl carboxylic acids or esters of such acids. Furthermore, the present disclosure provides a process to produce this polymorphic Form B substantially free of Form A and its preparation and use for pharmaceutical compositions. This process as well as the specific crystalline form is uncommon, improved and industrially advantageous. Furthermore, the disclosure relates to pharmaceutical compositions and uses thereof.