Aplaviroc
Overview
Description
Aplaviroc is a compound that belongs to the class of 2,5-diketopiperazines. It was developed as a CCR5 entry inhibitor for the treatment of HIV infection. The compound was designed to block the entry of the virus into human cells by targeting the CCR5 receptor, which is a critical co-receptor for HIV-1 entry .
Scientific Research Applications
Aplaviroc has been extensively studied for its potential in treating HIV infection. Its primary application is in inhibiting the entry of the virus into human cells by blocking the CCR5 receptor. This makes it a valuable tool in both clinical and research settings for studying HIV entry mechanisms and developing new therapeutic strategies .
Additionally, this compound has shown potential in other areas of research, such as:
Chemistry: As a model compound for studying spiro-diketopiperazine chemistry.
Biology: For investigating CCR5 receptor biology and its role in various diseases.
Mechanism of Action
Aplaviroc is a novel CCR5 receptor antagonist that binds specifically to human CCR5 . It binds to human CCR5 with a unique profile, as evidenced by the selective inhibition of monoclonal antibody binding . This mechanism of action is different from currently available classes of HIV drugs, which bind to viral enzymes in cells .
Preparation Methods
Synthetic Routes and Reaction Conditions: The synthesis of aplaviroc involves multiple steps, starting with the preparation of the spiro-diketopiperazine core. This core is then functionalized with various substituents to achieve the final structure. The key steps include:
- Formation of the diketopiperazine ring.
- Introduction of the butyl and cyclohexyl groups.
- Attachment of the phenoxybenzoic acid moiety.
Industrial Production Methods: Industrial production of this compound would likely involve optimization of the synthetic route to maximize yield and purity. This includes the use of high-efficiency catalysts, controlled reaction conditions, and purification techniques such as crystallization and chromatography .
Chemical Reactions Analysis
Types of Reactions: Aplaviroc undergoes several types of chemical reactions, including:
Oxidation: The hydroxyl group on the cyclohexyl ring can be oxidized to a ketone.
Reduction: The diketopiperazine ring can be reduced under specific conditions.
Substitution: The phenoxy group can be substituted with other functional groups.
Common Reagents and Conditions:
Oxidation: Reagents such as potassium permanganate or chromium trioxide.
Reduction: Reagents like sodium borohydride or lithium aluminum hydride.
Substitution: Various nucleophiles under basic or acidic conditions.
Major Products: The major products formed from these reactions depend on the specific conditions and reagents used. For example, oxidation of the hydroxyl group would yield a ketone, while substitution reactions could introduce a variety of functional groups .
Comparison with Similar Compounds
Maraviroc: Another CCR5 antagonist used in HIV treatment.
Vicriviroc: A CCR5 antagonist in late clinical trials.
PRO140: A monoclonal antibody against CCR5.
Comparison: Aplaviroc is unique in its chemical structure, particularly the spiro-diketopiperazine core, which distinguishes it from other CCR5 antagonists like maraviroc and vicriviroc. While all these compounds target the same receptor, this compound’s specific binding profile and allosteric inhibition mechanism provide distinct advantages and challenges, such as its potent antiviral activity and issues with hepatotoxicity .
Properties
IUPAC Name |
4-[4-[[(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl]methyl]phenoxy]benzoic acid |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C33H43N3O6/c1-2-3-19-36-30(38)28(29(37)24-7-5-4-6-8-24)34-32(41)33(36)17-20-35(21-18-33)22-23-9-13-26(14-10-23)42-27-15-11-25(12-16-27)31(39)40/h9-16,24,28-29,37H,2-8,17-22H2,1H3,(H,34,41)(H,39,40)/t28-,29-/m1/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
GWNOTCOIYUNTQP-FQLXRVMXSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCCCN1C(=O)C(NC(=O)C12CCN(CC2)CC3=CC=C(C=C3)OC4=CC=C(C=C4)C(=O)O)C(C5CCCCC5)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
CCCCN1C(=O)[C@H](NC(=O)C12CCN(CC2)CC3=CC=C(C=C3)OC4=CC=C(C=C4)C(=O)O)[C@@H](C5CCCCC5)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C33H43N3O6 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID6047317 |
Source
|
| Record name | Aplaviroc | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6047317 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
577.7 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Mechanism of Action |
GW873140 is a novel CCR5 receptor antagonist that binds specifically to human CCR5. It binds to human CCR5 with a unique profile as evidenced by the selective inhibition of monoclonal antibody binding. One of the many ways in which CCR5 inhibitors differ from the currently available classes of HIV drugs is that they bind to the host (CCR5 receptor), the cell, target rather than to the viral enzymes in cells like the CD4 cell. |
Source
|
| Record name | Aplaviroc | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB06497 | |
| 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) | |
CAS No. |
461443-59-4 |
Source
|
| Record name | Aplaviroc | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=461443-59-4 | |
| 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 | Aplaviroc [INN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0461443594 | |
| 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 | Aplaviroc | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB06497 | |
| 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 | Aplaviroc | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6047317 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | APLAVIROC | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/98B425P30V | |
| 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. | |
Retrosynthesis Analysis
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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
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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.
![2-Ethoxy-4-[2-[[3-methyl-1-(2-piperidin-1-ylphenyl)butyl]amino]-2-oxoethyl]benzoic acid](/img/structure/B1665065.png)
