Maraviroc

Base Information

• Chemical Name: Maraviroc
• CAS No.: 376348-65-1
• Deprecated CAS: 674782-29-7
• Molecular Formula: C29H41F2N5O
• Molecular Weight: 513.674
• Hs Code.: 2934999090
• UNII: MD6P741W8A,A3C7SRV8DV
• DSSTox Substance ID: DTXSID8048949
• Nikkaji Number: J2.198.465E
• Wikipedia: Maraviroc
• Wikidata: Q421369
• NCI Thesaurus Code: C73144
• RXCUI: 620216
• Pharos Ligand ID: VTLAW2L6LNCV,VTLGFSZK23QF,VTLHW7LQ6KZZ
• ChEMBL ID: CHEMBL1201187,CHEMBL256907,CHEMBL584744
• Mol file: 376348-65-1.mol

Synonyms:4,4-difluoro-N-((1S)-3-(exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo(3.2.1)oct-8-yl)-1-phenylpropyl)cyclohexanecarboxamide;maraviroc;Selzentry;UK 427,857;UK 427857;UK-427,857;UK-427857;UK427,857;UK427857

Chemical Property of Maraviroc

Chemical Property:

• Appearance/Colour: Brown solid
• Melting Point: 79-81 °C
• Refractive Index: 1.627
• PKA: 7.3(at 25℃)
• PSA: 63.05000
• Density: 1.29 g/cm³
• LogP: 6.27970
• Storage Temp.: Store at +4°C
• Solubility.: DMSO: >30mg/mL
• XLogP3: 5.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 8
• Exact Mass: 513.32791727
• Heavy Atom Count: 37
• Complexity: 751

Purity/Quality:

99% ^*data from raw suppliers

Maraviroc ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 48/22
• Safety Statements: 22-36

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: CC1=NN=C(N1C2CC3CCC(C2)N3CCC(C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C
• Isomeric SMILES: CC1=NN=C(N1C2C[C@H]3CC[C@@H](C2)N3CC[C@@H](C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C
• Recent ClinicalTrials: Trial to Evaluate the Safety and Efficacy of Maraviroc in Patients Hospitalized for Coronavirus Disease 2019 (COVID-19)
• Recent EU Clinical Trials: Bicentric, phase 2, randomized, open-label study to evaluate the efficacy and safety of maraviroc associated with standard treatment in hospitalized patients with pulmonary SARS-CoV-2 infection (COVID-19).
• Recent NIPH Clinical Trials: antiretroviral therapy regimen intensified with maraviroc during early HIV-1 infection
• Description: Maraviroc is the first CCR5 receptor antagonist that has been developed and launched for the treatment of HIV-1. Maraviroc binds in a slowly reversible, allosteric manner to CCR5, which is one of two principle chemokine co-receptors for viral entry into the host cell, the other being CXCR4. Binding of maraviroc to CCR5 induces conformational changes within the chemokine receptor, thereby preventing CCR5 binding to the viral gp120 protein and the ultimate CCR5- mediated virus-cell fusion that is a prerequisite for HIV invasion. Maraviroc, with its unique mechanism of action as a fusion inhibitor, joins the greater than 20 marketed antiretrovirals, including nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and PIs. It is approved for use in combination with these other antiretroviral drugs in adult patients with R5-tropic HIV-1 infection (but not X4 or dual/mixed tropic HIV-1).
• Uses: Maraviroc is a potent, non-competitive CCR5 receptor antagonist; inhibits binding of HIV viral coat protein gp120. Antiviral. Potent, non-competitive CCR5 receptor antagonist; inhibits binding of HIV viral coat protein gp120. Antiviral Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively
• Clinical Use: Treatment of HIV infection (in combination with other antiretroviral drugs) in treatment-experienced patients On November 20, 2009, the US Food and Drug Administration approved a supplemental new drug application to expand the indication for maraviroc to include combination antiretroviral treatment of treatmentnaive adults infected with CCR5-tropic HIV virus
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration possibly increased by clarithromycin and telithromycin, consider reducing dose of maraviroc; concentration reduced by rifampicin, consider increasing dose of maraviroc. Antidepressants: concentration possibly reduced by St John’s wort - avoid. Antifungals: concentration increased by ketoconazole. Antivirals: concentration increased by atazanavir, cobicistat, darunavir, indinavir, lopinavir and saquinavir - consider reducing maraviroc dose; concentration reduced by efavirenz - consider increasing dose of maraviroc; concentration of fosamprenavir reduced - avoid. Orlistat: absorption possibly reduced by orlistat.

Technology Process of Maraviroc

There total 55 articles about Maraviroc which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 91.0%

4,4-difluorocyclohexanecarboxylic acid (3-oxo-1-phenyl-propyl)-amide (376348-78-6) + exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane p-toluenesulfonate (423165-08-6,1545932-86-2) → maraviroc (376348-65-1,674782-29-7)

Guidance literature:

With sodium tris(acetoxy)borohydride; In ethyl acetate; at 0 - 15 ℃; for 2h; Inert atmosphere; Large scale;

DOI:10.1021/op800062d

Reference yield: 82.0%

(S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine (376348-71-9) + 4,4-difluorocyclohexane-1-carbonyl chloride (376348-75-3) → maraviroc (376348-65-1,674782-29-7)

Guidance literature:

With sodium carbonate; In dichloromethane; water; at 0 - 20 ℃;

DOI:10.1002/adsc.201000287

Reference yield: 75.0%

4,4-difluorocyclohexanecarboxylic acid (122665-97-8) + (S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine (376348-71-9) → maraviroc (376348-65-1,674782-29-7)

Guidance literature:

With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20 ℃; for 12h;

DOI:10.1002/ejoc.201800120

upstream raw materials:

4,4-difluorocyclohexanecarboxylic acid

(S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine

ethyl 4,4-difluorocyclohexane-1-carboxylate

tert-butyl (1S)-3-[3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-exo-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropylcarbamate

Refernces

• 1、 Andrews, Keith G.,Denton, Ross M.,Hirst, David J.,Stoll, Emma L.,Tongue, Thomas,Valette, Damien. "A practical catalytic reductive amination of carboxylic acids". . p. 9494 - 9500. Retrieved 2020/10/02.
• 2、 Zhou, Shengbin,Wang, Shuni,Wang, Jiang,Nian, Yong,Peng, Panfeng,Soloshonok, Vadim A.,Liu, Hong. "Configurationally Stable (S)- and (R)-α-Methylproline-Derived Ligands for the Direct Chemical Resolution of Free Unprotected β3-Amino Acids". . p. 1821 - 1832. Retrieved 2018/04/27.