481-37-8

Usage

Uses

Used in Pharmaceutical Industry:
ECGONINE HYDROCHLORIDE AMINO ALCOHOL PORTION is used as an intermediate compound in the synthesis of various pharmaceutical drugs, particularly those related to the tropane alkaloid family. Its unique chemical structure allows for the development of medications with potential applications in treating various medical conditions.
Used in Research and Development:
In the field of scientific research, ECGONINE HYDROCHLORIDE AMINO ALCOHOL PORTION is utilized as a key component in the study of the chemical properties, synthesis, and pharmacological effects of tropane alkaloids. ECGONINE HYDROCHLORIDE AMINO ALCOHOL POR TION aids researchers in understanding the mechanisms of action, potential side effects, and therapeutic applications of drugs derived from this class of alkaloids.
Used in Drug Metabolism Studies:
ECGONINE HYDROCHLORIDE AMINO ALCOHOL PORTION is employed in the investigation of drug metabolism, specifically in the context of cocaine and its metabolites. By studying the metabolic pathways and the role of ECGONINE HYDROCHLORIDE AMINO ALCOHOL POR TION, researchers can gain insights into the detoxification processes, potential drug interactions, and the development of addiction and dependence.
Used in Forensic Analysis:
In forensic science, ECGONINE HYDROCHLORIDE AMINO ALCOHOL PORTION can be used as a biomarker for the detection and identification of cocaine use. Its presence in biological samples, such as blood, urine, or hair, can provide evidence of drug consumption, aiding in the investigation of drug-related crimes and the assessment of drug abuse patterns.
Used in Drug Addiction Treatment:
ECGONINE HYDROCHLORIDE AMINO ALCOHOL PORTION may be utilized in the development of novel treatment strategies for drug addiction, particularly cocaine addiction. By understanding the role of ECGONINE HYDROCHLORIDE AMINO ALCOHOL POR TION in the metabolism and pharmacological effects of cocaine, researchers can potentially design medications or therapies that target the metabolic pathways involved, thereby reducing the addictive potential of the drug and aiding in the recovery process.

InChI:InChI=1/C9H15NO3/c1-10-5-2-3-6(10)8(9(12)13)7(11)4-5/h5-8,11H,2-4H2,1H3,(H,12,13)/t5?,6?,7-,8?/m0/s1

Upstream product

• 65-85-0 benzoic acid 
• 481-38-9 (+)-pseudoecgonine 
• 519-09-5 benzylecgonine 
• 50-36-2 Cocaine 
• 38969-40-3 Ecgonine methyl ester hydrochloride 
• 7143-09-1 methyl ecgonine 
• 53-21-4 (-)-cocaine hydrochloride 
• 7647-01-0 hydrogenchloride 
• 490-17-5 2,4-diphenyl-cyclobutane-1,3-dicarboxylic acid bis-(2-methoxycarbonyl-tropan-3-yl ester) 
• 490-15-3 3,4-diphenyl-cyclobutane-1,2-dicarboxylic acid bis-(2-methoxycarbonyl-tropan-3-yl ester),β-truxinic acid bis-(2-methoxycarbonyl-tropyl ester) 
• 7664-93-9 sulfuric acid 
• 484-93-5 ecgonidine 
• 50763-21-8 cis-cinnamoylcocaine 
• 50763-20-7 trans-cinnamoylcocaine 

Downstream Products

• 70939-97-8 ecgonine ethyl ester 
• 68406-46-2 (1R)-3exo-trans-cinnamoyloxy-tropane-2exo-carboxylic acid 
• 490-17-5 2,4-diphenyl-cyclobutane-1,3-dicarboxylic acid bis-(2-methoxycarbonyl-tropan-3-yl ester) 
• 72393-99-8 anhydroecgonine acid chloride 
• 519-09-5 benzylecgonine 
• 130342-80-2 2β-carbomethoxy-3β-(4-chlorophenyl)tropane 
• 146725-33-9 O 374 
• 387357-13-3 N-[4-(4-aminophenyl)butyl]-2β-carbomethoxy-3β-(4-chlorophenyl)tropane 
• 387357-12-2 N-[4-(4-nitrophenyl)butyl]-2β-carbomethoxy-3β-(4-chlorophenyl)tropane 
• 387357-14-4 N-[4-(3-iodo-4-aminophenyl)butyl]-2β-carbomethoxy-3β-(4-chlorophenyl)tropane 
• 71387-58-1 3-hydroxy-cocaine 
• 73208-20-5 C₉H₁₂ClNO*ClH 
• 900146-74-9 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-mesyloxyethyl)nortropane 
• 281667-94-5 FECNT 

Relevant academic research and scientific papers

Augmenting the efficacy of anti-cocaine catalytic antibodies through chimeric hapten design and combinatorial vaccination

Given the need for further improvements in anti-cocaine vaccination strategies, a chimeric hapten (GNET) was developed that combines chemically-stable structural features from steady-state haptens with the hydrolytic functionality present in transition-state mimetic haptens. Additionally, as a further investigation into the generation of an improved bifunctional antibody pool, sequential vaccination with steady-state and transition-state mimetic haptens was undertaken. While GNET induced the formation of catalytically-active antibodies, it did not improve overall behavioral efficacy. In contrast, the resulting pool of antibodies from GNE/GNT co-administration demonstrated intermediate efficacy as compared to antibodies developed from either hapten alone. Overall, improved antibody catalytic efficiency appears necessary to achieve the synergistic benefits of combining cocaine hydrolysis with peripheral sequestration.

Prediction of stability in pharmaceutical preparations. XX: Stability evaluation and bioanalysis of cocaine and benzoylecgonine by high-performance liquid chromatography

Specific, sensitive, reverse-phase high-performance liquid chromatographic (HPLC) assays of cocaine (I) and its hydrolysis products, benzoylecgonine (II) and benzoic acid (III), have been devised with analytical sensitivities as low as 15 ng/ml of plasma for I using spectrophotometric detection at 232 nm. Cocaine can be separated from its hydrolysis products by extraction at pH 7.5 with haloalkanes. Benzoylecgonine and benzoic acid can be extracted at pH 3.0 with 1-butanol. The evaporated residues were reconstituted in acetonitrile-water for HPLC assay. The assay was used to determine the stabilities of I and II in aqueous solutions, to establish log k-pH profiles at various temperatures, and to evaluate Arrhenius' parameters. Hydrolyses were by specific acid-base catalysis. Cocaine showed hydrogen and hydroxyl ion attack on protonated I with 40 and 90% proceeding through the benzoylecgonine route, respectively, as well as hydroxyl ion attack on neutral cocaine, with only 6% proceeding through the benzoylecgonine route. Cocaine is relatively unstable in the neutral pH range with a half-life of 5 hr in buffer at pH 7.25 and 40°. Similar half-lives were observed in fresh dog plasma at 300 and 30 μg/ml, although one study at 0.5 μg/ml indicated a doubling of the rate.

Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase

Benzoylecgonine (BZE) is the major toxic metabolite of cocaine and is responsible for the long-term cocaine-induced toxicity owing to its long residence time in humans. BZE is also the main contaminant following cocaine consumption. Here, we identified the bacterial cocaine esterase (CocE) as a BZE-metabolizing enzyme (BZEase), which can degrade BZE into biological inactive metabolites (ecgonine and benzoic acid). CocE was redesigned by a reactant-state-based enzyme design theory. An encouraging mutant denoted as BZEase2, presented a >400-fold improved catalytic efficiency against BZE compared with wild-type (WT) CocE. In vivo, a single dose of BZEase2 (1 mg kg?1, IV) could eliminate nearly all BZE within only two minutes, suggesting the enzyme has the potential for cocaine overdose treatment and BZE elimination in the environment by accelerating BZE clearance. The crystal structure of a designed BZEase was also determined.

Radical cyclization strategies for the formation of ring constrained tricyclic tropane analogues

A concise and efficient method for the construction of N,C3-constrained tropane derivatives has been developed. The key step of the reaction sequence involves either a 6- or a 7-trig radical cyclization. (C) 2000 Published by Elsevier Science Ltd.

68Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System

The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of 68Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [68Ga]Ga-HBED-hexadiyne-tropane, showed an IC50 value of 66 nM, together with a log D7.4 of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.

BOLAAMPHIPHILIC COMPOUNDS, COMPOSITIONS AND USES THEREOF

Bolaamphiphilic compounds are provided according to formula (I); where HG1, HG2 and L1 are as defined herein. Provided bolaamphiphilic compounds and the pharmaceutical compositions thereof are useful for delivering GDNF or NGF into animal or human brain.

BOLAAMPHIPHILIC COMPOUNDS, COMPOSITIONS AND USES THEREOF

Bolaamphiphilic compounds are provided according to formula (I): where HG1, HG2 and L1 are as defined herein. Provided bolaamphilphilic compounds and the pharmaceutical compositions thereof are useful for delivering GDNF or NGF into animal or human brain.

Synthesis of novel halo and tosyloxy nortropane derivatives as efficient precursors for the one-step synthesis of the dopamine transporter PET ligand [18F]FECNT

The fluorine-18 labeled nortropane derivative 2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (FECNT) is a dopamine transporter (DAT) ligand. Currently, it is considered as reference for positron emission tomography imaging. Herein, the synthesis of novel precursors (N-tosyloxy-, chloro-, and bromo- analogues) for one-step radiosynthesis of [ 18F]FECNT is reported. Using the N-mesyloxy- precursor in a one-step radiosynthesis, the crude [18F]FECNT was obtained with the radiolabeling yield of 45 ± 10%, confirming the practical efficiency of this approach in the design of novel precursors for labeling. Copyright

[11C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient 11C-O-methylation and initial small animal PET studies

PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [11C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [11C]MeI mediated synthesis of [11C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb2CO3 in DMF in up to 95 ± 5% labelling yield. A preliminary μPET-experiment demonstrates the reversible, highly specific binding of [11C]PR04.MZ in the brain of a male Sprague-Dawley rat.

Synthesis and monoamine uptake inhibition of conformationally constrained 2β-carbomethoxy-3β-phenyl tropanes

A series of 2β-carbomethoxy-3β-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine transporter (hDAT), the human serotonin transporter (hSERT) and the human noradrenalin transporter (hNET), stably expressed in human embryonic kidney cells (HEK). A SAR-study was conducted to determine the contribution of extended, 4-fluorinated, conformationally constrained C4 chains at the tropane nitrogen to human monoamine transporter affinity and selectivity. The Royal Society of Chemistry 2009.