Dexverapamil

Cat. No.: B1218737

CAS No.: 38321-02-7

M. Wt: 454.6 g/mol

InChI Key: SGTNSNPWRIOYBX-HHHXNRCGSA-N

Attention: For research use only. Not for human or veterinary use.

In Stock

Click on QUICK INQUIRY to receive a quote from our team of experts.
With the quality product at a COMPETITIVE price, you can focus more on your research.

Overview

1. Description

8. Comparison with similar compounds

2. Scientific research applications

9. Properties

3. Mechanism of action

10. Synthesis routes and methods I

4. Future directions

11. Synthesis routes and methods II

5. Biochemical analysis

12. Synthesis routes and methods III

6. Preparation methods

13. Retrosynthesis analysis

7. Chemical reactions analysis

14. Disclaimer

Description

It is a small molecule with the chemical formula C27H38N2O4 and a molecular weight of 454.61 g/mol . Dexverapamil is primarily known for its role as a chemosensitizer and modulator of multidrug resistance in cancer therapy .

Scientific Research Applications

Dexverapamil has a wide range of scientific research applications, including:

Chemistry: this compound is used as a chiral resolving agent in various chemical reactions and processes.

Biology: In biological research, this compound is used to study the mechanisms of multidrug resistance in cancer cells.

Medicine: this compound is investigated for its potential to enhance the efficacy of cancer chemotherapy by reversing multidrug resistance.

Industry: This compound is used in the pharmaceutical industry for the development of new drugs and formulations targeting multidrug resistance in cancer.

Mechanism of Action

Future Directions

Orally administrated Dexverapamil has shown potential beneficial effects on -cell preservation in new-onset type 1 diabetes. Furthermore, observational data suggest a reduced risk of type 2 diabetes development. More research is needed to fully understand the potential of this compound in these areas.

Biochemical Analysis

Biochemical Properties

Dexverapamil plays a significant role in biochemical reactions by inhibiting the P-glycoprotein (MDR-1, EC 3.6.3.44). This inhibition can potentially increase the effectiveness of a wide range of antineoplastic drugs that are inactivated by MDR-1 mechanisms . This compound interacts with various enzymes and proteins, including P-glycoprotein, and inhibits its function, thereby preventing the efflux of drugs from cells and increasing their intracellular concentration .

Cellular Effects

This compound has been shown to influence various cellular processes. It can modulate cell signaling pathways, gene expression, and cellular metabolism. For instance, in the context of type 1 diabetes, verapamil (a related compound) has been found to regulate the thioredoxin system and promote an anti-oxidative, anti-apoptotic, and immunomodulatory gene expression profile in human islets . This compound’s inhibition of P-glycoprotein can also lead to increased intracellular concentrations of chemotherapeutic agents, enhancing their cytotoxic effects on cancer cells .

Molecular Mechanism

At the molecular level, this compound exerts its effects primarily by inhibiting the P-glycoprotein efflux pump. This inhibition prevents the efflux of chemotherapeutic drugs from cancer cells, thereby increasing their intracellular concentration and enhancing their cytotoxic effects . This compound also interacts with other biomolecules, such as enzymes involved in drug metabolism, which can further influence its pharmacological effects .

Temporal Effects in Laboratory Settings

In laboratory settings, the effects of this compound can change over time. Studies have shown that the maximum tolerated dose of this compound is 900 mg/m²/day, with median plasma concentrations of this compound and its metabolite nor-dexverapamil being 1.2 and 1.4 μM, respectively . Over time, the expression of MDR-1 can increase, which may influence the effectiveness of this compound in inhibiting drug efflux . Long-term studies are needed to fully understand the stability, degradation, and long-term effects of this compound on cellular function.

Dosage Effects in Animal Models

The effects of this compound vary with different dosages in animal models. For instance, in studies involving EPOCH-refractory lymphomas, this compound was administered at escalating doses from 240 to 1200 mg/m² per day . The maximum tolerated dose was found to be 900 mg/m²/day, with higher doses potentially leading to toxic or adverse effects . The effectiveness of this compound in reversing multidrug resistance was observed at these dosages, highlighting its potential therapeutic benefits .

Metabolic Pathways

This compound is involved in various metabolic pathways, including N-demethylation by the enzyme CYP3A4. This metabolic pathway produces R- and S-norverapamil, which have plasma concentrations that are barely detectable following intravenous administration but can be equal to or exceed those of the parent drug enantiomers . The metabolism of this compound can influence its pharmacokinetics and pharmacodynamics, affecting its overall therapeutic efficacy .

Transport and Distribution

This compound is transported and distributed within cells and tissues through interactions with transporters such as P-glycoprotein. This transporter plays a crucial role in limiting the cellular uptake and distribution of this compound, thereby influencing its bioavailability and therapeutic effects . The inhibition of P-glycoprotein by this compound can enhance the intracellular accumulation of chemotherapeutic drugs, improving their efficacy .

Subcellular Localization

The subcellular localization of this compound is influenced by its interactions with various cellular components. This compound can localize to specific compartments or organelles within the cell, depending on the presence of targeting signals or post-translational modifications . Understanding the subcellular localization of this compound is essential for elucidating its mechanisms of action and optimizing its therapeutic potential.

Preparation Methods

Dexverapamil can be synthesized through various synthetic routes. One common method involves the resolution of racemic verapamil into its enantiomers. The reaction conditions typically involve the use of chiral resolving agents and chromatographic techniques to separate the ®-enantiomer from the (S)-enantiomer . Industrial production methods may involve large-scale resolution processes and purification steps to obtain high-purity this compound.

Chemical Reactions Analysis

Dexverapamil undergoes several types of chemical reactions, including:

Oxidation: this compound can be oxidized to form various metabolites. Common reagents for oxidation include hydrogen peroxide and other oxidizing agents.

Reduction: Reduction reactions can convert this compound into its reduced forms. Reducing agents such as sodium borohydride are commonly used.

Substitution: this compound can undergo substitution reactions where functional groups are replaced by other groups. Common reagents include halogens and nucleophiles.

Hydrolysis: Hydrolysis reactions can break down this compound into its constituent parts.

Comparison with Similar Compounds

Dexverapamil is unique compared to other similar compounds due to its specific enantiomeric form and its ability to modulate multidrug resistance. Similar compounds include:

Verapamil: The racemic mixture of ®- and (S)-verapamil, used primarily as a calcium channel blocker for cardiovascular conditions.

Norverapamil: A metabolite of verapamil with similar pharmacological properties.

Diltiazem: Another calcium channel blocker with similar cardiovascular effects but different chemical structure.

This compound’s uniqueness lies in its specific action on the P-glycoprotein efflux pump and its potential to enhance the efficacy of chemotherapeutic agents in cancer treatment .

Properties

IUPAC Name	(2R)-2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

InChI	InChI=1S/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3/t27-/m1/s1	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

InChI Key	SGTNSNPWRIOYBX-HHHXNRCGSA-N	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Canonical SMILES	CC(C)C(CCCN(C)CCC1=CC(=C(C=C1)OC)OC)(C#N)C2=CC(=C(C=C2)OC)OC	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Isomeric SMILES	CC(C)[C@@](CCCN(C)CCC1=CC(=C(C=C1)OC)OC)(C#N)C2=CC(=C(C=C2)OC)OC	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Molecular Formula	C27H38N2O4	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

DSSTOX Substance ID	DTXSID501009404	Source
Record name	Dexverapamil
Source	EPA DSSTox
URL	https://comptox.epa.gov/dashboard/DTXSID501009404
Description	DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.

Molecular Weight	454.6 g/mol	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

CAS No.	38321-02-7	Source
Record name	(R)-Verapamil
Source	CAS Common Chemistry
URL	https://commonchemistry.cas.org/detail?cas_rn=38321-02-7
Description	CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society.
Explanation	The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.

Record name	Dexverapamil [INN]
Source	ChemIDplus
URL	https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0038321027
Description	ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system.

Record name	Dexverapamil
Source	DrugBank
URL	https://www.drugbank.ca/drugs/DB14063
Description	The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information.
Explanation	Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)

Record name	Dexverapamil
Source	EPA DSSTox
URL	https://comptox.epa.gov/dashboard/DTXSID501009404
Description	DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.

Record name	(+)-3-(3,4-dimethoxyphenyl)-6-[(5,6-dimethoxyphenethyl)methylamino]hexane-3-carbonitrile
Source	European Chemicals Agency (ECHA)
URL	https://echa.europa.eu/substance-information/-/substanceinfo/100.048.963
Description	The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness.
Explanation	Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.

Record name	DEXVERAPAMIL
Source	FDA Global Substance Registration System (GSRS)
URL	https://gsrs.ncats.nih.gov/ginas/app/beta/substances/QR5PYD126V
Description	The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions.
Explanation	Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.

Synthesis routes and methods I

Procedure details

Verapamil hydrochloride was added to a solution of 25% deuterated sulfuric acid in deuterated water (v/v) and deuterated methanol. The solution was stirred for 140 hours at 90° C. The pH was adjusted to 12.0 and the mixture extracted with ethyl acetate. The combined ethyl acetate extracts were washed with water, dried over magnesium sulfate and evaporated to yield a viscous oil. This oil was dissolved in ether and ethereal hydrochloride was added to precipitate the hydrochloride salt. The salt was collected by filtration and crystallized from ethyl acetate to obtain deuterated verapamil as a white solid.

Name

Verapamil hydrochloride

Quantity

0 (± 1) mol

Type

reactant

Reaction Step One

[Compound]

Name

deuterated sulfuric acid

Quantity

0 (± 1) mol

Type

reactant

Reaction Step One

Name

deuterated water

Quantity

0 (± 1) mol

Type

solvent

Reaction Step One

[Compound]

Name

deuterated methanol

Quantity

0 (± 1) mol

Type

solvent

Reaction Step One

Name

hydrochloride

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Two

Name

ether

Quantity

0 (± 1) mol

Type

solvent

Reaction Step Three

Name

verapamil

Details

Synthesis routes and methods II

Procedure details

In carrying out this synthesis, the following materials were used. Homovanillyl alcohol, Aldrich, 99%, Cat. No. 148830-10G, Batch No. 19516EO; potassium carbonate, Aldrich, 99%; triethylamine, Aldrich, 99.5%, Cat. No. 471283-500 mL, Batch No. 04623HD; methanesulfonyl chloride, Aldrich, 99.5%, Cat. No. 471259-500 mL, Batch No. 13209KC; 3,4-dimethoxyphenylacetonitrile, Aldrich, Cat. No. 126349-100G, Batch No. 08011BD; 2-iodopropane, Aldrich, 99%, Cat. No. 148938-100G, Batch #, 03604DD; diisopropylamine, redistilled, Aldrich, 99.95%, Cat. No. 386464-100 mL, Batch #00944TD; butyllithium, 1.6 M solution in hexanes, Aldrich, Cat. No. 186171-100 mL, Batch #20709PD; 3-bromo-1-propanol, Aldrich, 97%, Cat. No. 167169-25G, Batch No. 0901DE; dichloromethane, Aldrich, Cat. No. 270997-2L, Batch #: 00434 KD; sodium triacetoxyborohydride, Aldrich, 95%, Cat. No. 316393-25G, Batch No. 07920LD; N,N-diisopropylethylamine, Aldrich, Cat. No. 387649-100 mL, Batch No. 06448PC.

Name

Homovanillyl alcohol

Quantity

0 (± 1) mol

Type

reactant

Reaction Step One

Name

potassium carbonate

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Two

Name

methanesulfonyl chloride

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Three

Name

3,4-dimethoxyphenylacetonitrile

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Four

Name

2-iodopropane

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Five

Name

triethylamine

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Six

Name

Verapamil

Details

Synthesis routes and methods III

Procedure details

Weighed quantities of verapamil hydrochloride and Eudragit L100 were mixed in a blender. The mass was granulated using molten compritol. Granules of verapamil thus obtained were further blended using Kollidon SR and lactose, lubricated using magnesium stearate and compressed into tablets.

Name

verapamil hydrochloride

Quantity

0 (± 1) mol

Type

reactant

Reaction Step One

Name

Eudragit

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Two

Name

verapamil

Details

Retrosynthesis Analysis

AI-Powered Synthesis Planning: Our tool employs the Template_relevance Pistachio, Template_relevance Bkms_metabolic, Template_relevance Pistachio_ringbreaker, Template_relevance Reaxys, Template_relevance Reaxys_biocatalysis model, leveraging a vast database of chemical reactions to predict feasible synthetic routes.

One-Step Synthesis Focus: Specifically designed for one-step synthesis, it provides concise and direct routes for your target compounds, streamlining the synthesis process.

Accurate Predictions: Utilizing the extensive PISTACHIO, BKMS_METABOLIC, PISTACHIO_RINGBREAKER, REAXYS, REAXYS_BIOCATALYSIS database, our tool offers high-accuracy predictions, reflecting the latest in chemical research and data.

Strategy Settings

Precursor scoring	Relevance Heuristic
Min. plausibility	0.01
Model	Template_relevance
Template Set	Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis
Top-N result to add to graph	6

Feasible Synthetic Routes

Reactant of Route 1

Dexverapamil

Reactant of Route 2

Dexverapamil

Reactant of Route 3

Dexverapamil

Reactant of Route 4

Dexverapamil

Reactant of Route 5

Dexverapamil

Reactant of Route 6

Dexverapamil

Disclaimer and Information on In-Vitro Research Products

Please be aware that all articles and product information presented on BenchChem are intended solely for informational purposes. The products available for purchase on BenchChem are specifically designed for in-vitro studies, which are conducted outside of living organisms. In-vitro studies, derived from the Latin term "in glass," involve experiments performed in controlled laboratory settings using cells or tissues. It is important to note that these products are not categorized as medicines or drugs, and they have not received approval from the FDA for the prevention, treatment, or cure of any medical condition, ailment, or disease. We must emphasize that any form of bodily introduction of these products into humans or animals is strictly prohibited by law. It is essential to adhere to these guidelines to ensure compliance with legal and ethical standards in research and experimentation.

Quick Inquiry

Name *

Email *

Phone

Country

Product Name

Quantity *

Message