Abstract: The disclosure is directed to deutetrabenazine analogs, compositions comprising same and methods of detecting same in compositions comprising deutetrabenazine.

Abstract: Disclosed herein are new dosage regimens for deuterium-substituted benzoquinoline compounds, and methods for the treatment of abnormal muscular activity, movement disorders, and related conditions.

Abstract: The disclosure is directed to deutetrabenazine analogs, compositions comprising same and methods of detecting same in compositions comprising deutetrabenazine.

Abstract: Disclosed herein are new dosage regimens for deuterium-substituted benzoquinoline compounds, and methods for the treatment of abnormal muscular activity, movement disorders, and related conditions.

Abstract: The present invention relates to deuterated compounds according to Formula I-A, Formula II-A, Formula II-D, and Formula III-A. These compounds can be used as PET imaging agents for evaluating Parkinson's Disease, Alzheimer Disease, and for determining specific serotonin reuptake inhibitor (SSRIi) activity for treatment of depression. The present invention also relates to pharmaceutical compositions comprising a pharmaceutical acceptable carrier and a compound of Formula I-A, Formulae II-A, Formula II-D, or Formula III-A, or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are processes for the preparation of (S)-(2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl 2-amino-3-methylbutanoate di(4-methylbenzenesulfonate), or a solvate, hydrate, or polymorph thereof.

Abstract: Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-?-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof wherein the patient is also being administered digoxin.

Abstract: The invention provides (+)-?-dihydrotetrabenazine succinate salt. Also provided are (+)-?-dihydrotetrabenazine succinate salt for use in medicine, pharmaceutical compositions comprising (+)-?-dihydrotetrabenazine succinate salt and a pharmaceutically acceptable excipient and the uses of (+)-?-dihydrotetrabenazine succinate salt as a VMAT2 receptor antagonist and in the treatment of a movement disorder such as Tourette's syndrome. The invention further provides a method for preparing the (+)-?-dihydrotetrabenazine succinate salt.

Abstract: The present invention relates to new methods of manufacturing benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), and intermediates thereof.

Abstract: The present invention provides process for preparation of dihydroxy benzoquinoline compound (III) comprising reacting dihydroxy isoquinoline compound (IV) or a salt thereof with (2-acetyl-4-methyl-pentyl)-trimethyl-ammonium iodide (V) and further converting it to tetrabenazine (I) and deutetrabenazine (II).

Abstract: Provided herein are processes for the preparation of (S)-(2R,3R,11bR-3-isobuty-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl 2-amino-3-methylbutanoate di(4-methylbenzenesulfonate), or a solvate, hydrate, or polymorph thereof.

Abstract: The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5 and R6 are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5, R6, X and Y are as described in the description and in the claims, as well as or pharmaceutically acceptable salts, or enantiomers, or diastereomers thereof. The invention also contains compositions including the compounds and methods of using the compounds.

Abstract: The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5 and R6 are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: The invention relates to a method for the synthesis of compounds of general formula (1A) and salts thereof wherein one of the R groups is an ?-sialyl moiety and the other is H, X1 represents a carbohydrate linker, A is a D-glucopyranosyl unit optionally substituted with fucosyl, R1 is a protecting group that is removable by hydrogenolysis, the integer m is 0 or 1, by a transsialidation reaction.

Abstract: This invention relates to a process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R1, R2, R3 and R4 are defined in the specification, comprising the optical resolution of an enamine of the formula wherein R1 is lower alkyl, in the presence of an optical active resolving agent to form an (S)-enamine salt of the formula wherein RCO2? is the conjugate base of the resolving agent.

Abstract: The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula wherein R2, R3 and R4 are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula wherein R1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula wherein R2, R3, R4 and Prot are as defined in the specification.

Abstract: The present invention is concerned with an improved process for the preparation of pyrido[2,1-a]isoquinoline derivatives of formula I wherein R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy or lower alkenyl, wherein lower alkyl, lower alkoxy and lower alkenyl may optionally be substituted by lower alkoxycarbonyl, aryl or heterocyclyl, and the pharmaceutically acceptable salts thereof. The invention also relates to two crystalline forms of (2S,3S,11bS)-1-(2-amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride, which are form A and form B and to an amorphous form of said compound.

Abstract: The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention relates to new pharmaceutical compositions comprising benzoquinoline compounds, and methods to inhibit vesicular monoamine transporter 2 (VMAT2) activity in a subject for the treatment of chronic hyperkinetic movement disorders.

Abstract: The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The invention relates to a process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R2, R3 and R4 are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula wherein R1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula wherein R2, R3, R4 and Prot are as defined in the specification.

Abstract: The present invention is concerned with an improved process for the preparation of pyrido[2,1-a]isoquinoline derivatives of formula I wherein R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy or lower alkenyl, wherein lower alkyl, lower alkoxy and lower alkenyl may optionally be substituted by lower alkoxycarbonyl, aryl or heterocyclyl, and the pharmaceutically acceptable salts thereof. The invention also relates to two crystalline forms of (2S,3S,11bS)-1-(2-amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride, which are form A and form B and to an amorphous form of said compound.

Abstract: Compound of formula I are antagonists of the PGD2 receptor, CRTH2, and as such are useful in the treatment and/or prevention of CRTH2-mediated diseases such as asthma.

Abstract: This invention relates to a process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R1, R2, R3 and R4 are defined in the specification, comprising the optical resolution of an enamine of the formula wherein R1 is lower alkyl, in the presence of an optical active resolving agent to form an (S)-enamine salt of the formula wherein RCO2? is the conjugate base of the resolving agent.

Abstract: The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

Abstract: This invention relates to a method of imaging vesicular monoamine transporters and to labeled compounds and pharmaceutical compositions thereof, and methods of making labeled compounds useful in imaging vesicular monoamine transporters. This invention also relates to compounds, and methods of monitoring progression of a disease related to vesicular monoamine transporters.

Abstract: The present invention is directed to tricyclic indole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by endothelial lipase, for example, cardiovascular disorders.

Abstract: The present invention relates to a method for preparing tetrabenazine (TBZ) and dihydrotetrabenazine (DTBZ), and more specifically to a method for preparing tetrabenazine (TBZ) and dihydrotetrabenazine (DTBZ) by using simple and short reaction processes of using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 4-methyl-2-(3-(trimethylsilyl)prop-1-ene-2-yl)pentane as starting materials to sequentially perform an alkylation reaction, an Aza-Prins cyclization reaction in the presence of an oxidant and an oxidation reaction.

Abstract: The invention relates to a process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R2, R3 and R4 are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula wherein R1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula wherein R2, R3, R4 and Prot are as defined in the specification.

Abstract: The present invention relates to a novel process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R2, R3 and R4 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy and lower alkenyl, wherein lower alkyl, lower alkoxy and lower alkenyl may optionally be substituted by a group consisting of lower alkoxycarbonyl, aryl and heterocyclyl, and the pharmaceutically acceptable salts thereof. The pyrido[2,1-a]isoquinoline derivatives of the formula I are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV.

Abstract: Substituted 3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol compounds are disclosed that are inhibitors of the vesicular monoamine transporter 2 (VMAT2). The compounds of this invention have the structure: wherein R1 is as defined herein, including stereoisomers and pharmaceutically acceptable salts and solvates thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use in a subject in need thereof.

Abstract: This invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula wherein R1, R2, R3 and R4 are defined in the specification, comprising the optical resolution of an enamine of the formula wherein R1 is lower alkyl, in the presence of an optical active resolving agent to form an (S)-enamine salt of the formula wherein RCO2? is the conjugate base of the resolving agent.

Abstract: The present invention is concerned with an improved process for the preparation of pyrido[2,1-a]isoquinoline derivatives of formula I wherein R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy or lower alkenyl, wherein lower alkyl, lower alkoxy and lower alkenyl may optionally be substituted by lower alkoxycarbonyl, aryl or heterocyclyl, and the pharmaceutically acceptable salts thereof. The invention also relates to two crystalline forms of (2S,3S,11b S)-1-(2-amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride, which are form A and form B and to an amorphous form of said compound.

Abstract: The present invention refers to pharmaceutical composition comprising a DPP-IV inhibitor.

Abstract: The present invention provides a two-photon light-emitting compound represented by formula (1), an optical data recording medium comprising a compound represented by formula (1), a two-photon polymerizable composition comprising a polymerizable monomer or polymerizable oligomer and at least compound represented by formula (1), and a photopolymerization process: X2—(—CR4?CR3—)m—C(?O)—(—CR1?CR2—)n—X1??(1) wherein X1 and X2 may be the same or different and each represent a substituted or unsubstituted aryl group or a substituted or unsubstituted heterocyclic group; R1, R2, R3 and R4 each independently represent a hydrogen atom or substituent; some of R1, R2, R3 and R4 may be connected to each other to form at least one ring; and n and m each independently represent an integer of from 1 to 4, with the proviso that when n and m are 2 or more, the plurality of R1's, R2's, R3's, and R4's each may be the same or different.

Abstract: The present invention relates to a novel process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R2, R3 and R4 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy and lower alkenyl, wherein lower alkyl, lower alkoxy and lower alkenyl may optionally be substituted by a group consisting of lower alkoxycarbonyl, aryl and heterocyclyl, and the pharmaceutically acceptable salts thereof. The pyrido[2,1-a]isoquinoline derivatives of the formula I are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV.

Abstract: This invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula wherein R1, R2, R3 and R4 are defined in the specification, comprising the optical resolution of an enamine of the formula wherein R1 is lower alkyl, in the presence of an optical active resolving agent to form an (S)-enamine salt of the formula wherein RCO2? is the conjugate base of the resolving agent.

Abstract: The invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula wherein R2, R3 and R4 are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula wherein R1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula wherein R2, R3, R4 and Prot are as defined in the specification.

Abstract: The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention provides, inter alia, a compound of formula I: wherein the substituent designations are indicated in the Specification. The present invention also provides pharmaceutical compositions comprising a compound of formula I, and methods of treatment or prevention of diabetes or hyperglycemia in a patient, and of normalizing blood glucose levels in a subject, by administering an effective amount of a compound of formula I.

Abstract: The present invention provides novel alpha-fluoroalkyl dihydrotetrabenazine compounds I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is hydrogen or a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; and R4 is a C1-C10 aliphatic radical, a C3-C10 cycloaliphatic radical, or a C3-C10 aromatic radical. The alpha-fluoroalkyl dihydrotetrabenazine compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl dihydrotetrabenazine compounds are believed to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl dihydrotetrabenazine compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl dihydrotetrabenazine compounds are useful as probes for the discovery of PET imaging agents.

Abstract: Substituted 3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol compounds are disclosed that are inhibitors of the vesicular monoamine transporter 2 (VMAT2). The compounds of this invention have the structure: wherein R1 is as defined herein, including stereoisomers and pharmaceutically acceptable salts and solvates thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use in a subject in need thereof.

Abstract: The present invention provides novel fluoroalkyl tetrabenazine carbinol compounds having structure I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; R4 is hydrogen or a C1-C10 aliphatic radical; and R5 is hydrogen, a C1-C10 aliphatic radical, a C2-C10 cycloaliphatic radical, or a C2-C20 aromatic radical. In a particular embodiment, —OR5 is an ester moiety. The fluoroalkyl tetrabenazine carbinol compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluoroalkyl tetrabenazine carbinol compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The fluoroalkyl tetrabenazine carbinol compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker.

Abstract: The present invention provides novel fluoroalkyl tetrabenazine carbinol compounds having structure I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; R4 is hydrogen or a C1-C10 aliphatic radical; and R5 is hydrogen, a C1-C10 aliphatic radical, a C2-C10 cycloaliphatic radical, or a C2-C20 aromatic radical. In a particular embodiment, —OR5 is an ester moiety. The fluoroalkyl tetrabenazine carbinol compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluoroalkyl tetrabenazine carbinol compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The fluoroalkyl tetrabenazine carbinol compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker.

Abstract: The present invention generally relates to luminescent and/or optically absorbing compositions and/or precursors to those compositions, including solid films incorporating these compositions/precursors, exhibiting increased luminescent lifetimes, quantum yields, enhanced stabilities and/or amplified emissions. The present invention also relates to sensors and methods for sensing analytes through luminescent and/or optically absorbing properties of these compositions and/or precursors. Examples of analytes detectable by the invention include electrophiles, alkylating agents, thionyl halides, and phosphate ester groups including phosphoryl halides, cyanides and thioates such as those found in certain chemical warfare agents. The present invention additionally relates to devices and methods for amplifying emissions, such as those produced using the above-described compositions and/or precursors, by incorporating the composition and/or precursor within a polymer having an energy migration pathway.

Abstract: The present invention relates to a process of the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one of the formula by employing a dialkylmalonate of the formula wherein R1b is lower alkyl, and the use of this process for the manufacture of DPP-IV inhibitors that are useful for the treatment and/or prophylaxis of diseases such as diabetes.

Abstract: The present invention provides, inter alia, dihydropyridone compounds and compositions, including analogs of a vesicular monoamine transporter type 2 (VMAT2) antagonist. The present invention also provides methods of using such compounds/analogs for modulating glucose levels, and/or preventing, treating, or ameliorating the effects of diabetes and hyper-glycemia.