1026016-83-0

Usage

Uses

Used in Pharmaceutical Industry:
2H-Benzo[a]quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, (3R,11bR)is used as a dopamine depleting agent for the treatment of movement disorders and psychiatric conditions. As an isomer of Tetrabenazine, it exhibits antidyskinetic and antipsychotic properties, making it a valuable therapeutic agent in the management of chorea, Huntington's disease, and other related disorders.
Used in Neurochemistry Research:
2H-Benzo[a]quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, (3R,11bR)is also utilized in neurochemistry research to study the mechanisms of dopamine depletion and its effects on various neurological conditions. The unique structure and stereochemistry of 2H-Benzo[a]quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, (3R,11bR)allow researchers to investigate its interactions with dopamine receptors and transporters, providing insights into the development of novel therapeutic strategies for neurological disorders.

Upstream product

• 58-46-8 (3R^*,11bR^*)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzoquinolizin-2-one 
• 1223399-57-2 (3R,11bR)-tetrabenazine D-camphorsulfonate 
• 35963-20-3 (R)-10-camphorsulfonic acid 
• 718635-93-9 tetrabenazine 
• 1091627-85-8 C₂₄H₃₇NO₅ 
• 244177-70-6 (4S,5R)-3-((2S,3R)-2-isobutyl-3-hydroxypent-4-enoyl)-4-methyl-5-phenyl-1,3-oxazolidin-2-on 
• 244177-76-2 (2S,3R)-3-(tert-butyldimethylsilanyloxy)-2-isobutylpent-4-enoic acid 
• 168540-62-3 (4S,5R)-3-(4-methylpentanoyl)-4-methyl-5-phenyl-1,3-oxazolidin-2-on 
• 244177-72-8 (2S,3R)-3-hydroxy-2-isobutylpent-4-enethioic acid S-benzyl ester 
• 203806-39-7 N-(tert-butoxycarbonyl)-2-(4,5-dimethoxy-2-vinylphenyl)ethylamine 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 66384-45-0 N-acetyl-2-iodo-4,5-dimethoxy-β-phenethylamine 
• 6275-29-2 N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide 
• 58432-84-1 2-(2-iodo-4,5-dimethoxyphenyl)acetonitrile 

Downstream Products

• 924854-60-4 (+)-β-DHTBZ 
• 862377-27-3 (2S,3S,11bR)-1,3,4,6,7,11b-hexahydro-9,10-methoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-ol 
• 862377-31-9 (2R,3S,11bR)-1,3,4,6,7,11b-hexahydro-9,10-methoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-ol 
• 1639208-54-0 (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl (S)-2-amino-3-methylbutanoate di(4-methylbenzenesulfonate) 
• 1147130-19-5 C₂₉H₄₁NO₄ 
• 1147130-24-2 C₂₈H₃₉NO₆S 
• 1147130-21-9 C₂₉H₄₁NO₆S 
• 1025504-76-0 (S)-2-benzyloxycarbonyl-amino-3-methylbutyric acid-(2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester 
• 1025504-45-3 (S)-2-amino-3-methylbutyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolizin-2-yl ester 

Relevant academic research and scientific papers

A concise total synthesis of (+)-tetrabenazine and (+)-α- dihydrotetrabenazine

Highly concise asymmetric total syntheses of (+)-tetrabenazine (1), a drug for the treatment of chorea associated with Huntington's disease, and of (+)α-dihydrotetrabenazine (2), an active metabolite of 1, have been accomplished. Our synthetic route features a trans-selective enol etherification, followed by an unprecedented cation-dependent aza-Claisen rearrangement to establish the carbon framework and two stereogenic centers of tetrabenazine. The syntheses consist of seven steps (34% overall yield) for (+)-2 and eight steps (22% overall yield) for (+)-l.

Asymmetric synthesis of tetrabenazine and dihydrotetrabenazine

(Chemical Equation Presented) The enantioselective synthesis of (+)-tetrabenazine (TBZ) and (+)-dihydrotetrabenazine (DTBZ), agents of significant interest for therapeutic and molecular imaging applications, has been completed in 21% (TBZ) and 16% (DTBZ)

Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors

Tetrabenazine (TBZ) ((±)-1) and dihydrotetrabenazines (DHTBZ) are potent inhibitors of VMAT2. Herein, a practical chemical resolution of (±)-1 and stereoselective synthesis of all eight DHTBZ stereoisomers are described. The result of VMAT2 binding assay revealed that (+)-1 (Ki = 4.47 nM) was 8000-fold more potent than (-)-1 (Ki = 36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: Ki = 3.96 nM) showed the greatest affinity for VMAT2. The (3R,11bR)-configuration appeared to play a key role for VMAT2 binding. In summary, (+)-1, (+)-2, and their derivatives warrant further studies in order to develop more potent and safer drugs for the treatment of chorea associated with Huntington's disease and other hyperkinetic disorders.

Preparation method of benzoquinolizine derivative

The invention relates to a preparation method of a benzoquinolizine derivative, belongs to the technical field of medicinal chemistry, and particularly relates to a chiral resolution method of tetrabenazine. (3R, 11bR)-tetrabenazine or (3S, 11bS)-tetrabenazine with high optical purity is simply, conveniently and effectively prepared by taking tetrabenazine racemate as a raw material through the steps of salifying with chiral acid, pulping, dissociating and the like. Compared with the prior art, the method has the advantages of mild reaction conditions in each step, high yield, simplicity and convenience in operation, stable process and suitability for large-scale industrial production.

Dynamic resolution method of tetrabenazine

The invention provides a dynamic resolution method of tetrabenazine, and belongs to the field of medicinal chemical industry. The method can be used for resolving tetrabenazine to obtain (3R,11bR)-tetrabenazine. The method comprises the following steps: mixing and reacting a resolving reagent is with tetrabenazine to obtain a desired configuration, performing separation, and then carrying out alkali dissociation to obtain the (3R,11bR)-tetrabenazine. The analytical method can effectively separate tetrabenazine, and has the advantages of high product purity, high yield, simplicity in operationand solvent recoverability.

SOLID STATE FORMS OF VALBENAZINE

Solid state forms of Valbenazine, Valbenazine salts, processes for preparation thereof and pharmaceutical compositions thereof are disclosed. Processes for the preparation of Valbenazine and intermediates in the preparation thereof are further described.

CRYSTALLINE VALBENAZINE FREE BASE

The present disclosure generally relates to crystalline valbenazine. The present disclosure also generally relates to a pharmaceutical composition comprising crystalline valbenazine, as well of methods of using crystalline valbenazine in the treatment of

A ring-closing metathesis-based approach to the synthesis of (+)-tetrabenazine

A modular stereoselective synthesis of the vesicular monoamine transport inhibitors (+)-tetrabenazine ((+)-1) and (+)-α-dihydrotetrabenazine ((+)-2) has been developed. The approach is based on amine 4 and acid 5 as the key building blocks, which were elaborated into macrolactam 3 by amide coupling and a subsequent highly E-selective RCM reaction. Macrolactam 3 could be converted into tetrabenazine in three known steps.

Preparation and characterization of tetrabenazine enantiomers against vesicular monoamine transporter 2

As a clinical medication for the treatment of hyperkinetic movement disorders, in conditions such as Huntington's disease, tetrabenazine (TBZ) has always been used in its racemic form. To establish whether or not its beneficial therapeutic actions are enantiospecific, a practical total synthetic route was developed to yield each enantiomeric form to allow their chemical and pharmacological characterization. We briefly summarize the total synthesis of TBZ and report a detailed procedure for resolution of TBZ into its enantiomers, (+)-TBZ and (-)-TBZ. This allowed determination of the optical rotation and absolute configurations of each TBZ enantiomer, based on X-ray crystallographic analysis, together with characterization of their inhibitory action at the vesicular monoamine transporter 2, where (+)-TBZ proved 3-fold more active than (-)-TBZ.

INTERMEDIATES FOR FLUORINATED DIHYDROTETRABENAZINE ETHER IMAGING AGENTS AND PROBES

The present invention provides novel fluorophilic compounds having structure VI wherein R1 is a C2-C20 aliphatic, a C3-C20 cycloaliphatic, or a C3-C20 aromatic radical comprising at least one functional group susceptible to reaction with nucleophilic fluoride ion or an electrophilic fluorinating agent; R2 is a C1-C10 aliphatic radical, or a C3-C10 cycloaliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; and R4 is hydrogen or a C1-C10 aliphatic radical. The fluorophilic compounds are provided in both racemic and enantiomerically enriched forms and are useful as intermediates in the preparation of novel PET imaging agents and probes useful in the discovery and performance assessment of PET imaging agents. The fluorophilic compounds are particularly useful in the preparation of PET imaging agents and probes having a high affinity for VMAT-2, a biomarker implicated in human diabetes and other illnesses such as Parkinson's disease.