Darunavir

Base Information

• Chemical Name: Darunavir
• CAS No.: 206361-99-1
• Deprecated CAS: 618109-00-5,1097732-88-1
• Molecular Formula: C₂₇H₃₇N₃O₇S
• Molecular Weight: 547.673
• European Community (EC) Number: 606-590-1
• UNII: YO603Y8113
• DSSTox Substance ID: DTXSID0046779
• Nikkaji Number: J2.037.394F
• Wikipedia: Darunavir
• Wikidata: Q3765251
• NCI Thesaurus Code: C65364
• RXCUI: 460132
• Metabolomics Workbench ID: 43470
• ChEMBL ID: CHEMBL1323
• Mol file: 206361-99-1.mol

Synonyms:114, TMC;darunavir;darunavir ethanolate;Ethanolate, Darunavir;Prezista;TMC 114;TMC-114;TMC114;UIC 94017;UIC-94017;UIC94017

Chemical Property of Darunavir

Chemical Property:

• Appearance/Colour: White amorphous solid
• Melting Point: 74-76 °C
• Refractive Index: 1.62
• PKA: 11.43±0.46(Predicted)
• PSA: 148.80000
• Density: 1.34 g/cm³
• LogP: 4.42820
• Storage Temp.: -20°C Freezer
• Solubility.: Soluble in DMSO (>25 mg/ml)
• XLogP3: 2.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 12
• Exact Mass: 547.23522170
• Heavy Atom Count: 38
• Complexity: 853

Purity/Quality:

99% ^*data from raw suppliers

Darunavir ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: CC(C)CN(CC(C(CC1=CC=CC=C1)NC(=O)OC2COC3C2CCO3)O)S(=O)(=O)C4=CC=C(C=C4)N
• Isomeric SMILES: CC(C)CN(C[C@H]([C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CO[C@@H]3[C@H]2CCO3)O)S(=O)(=O)C4=CC=C(C=C4)N
• Recent ClinicalTrials: Study of Cobicistat-Boosted Atazanavir (ATV/co), Cobicistat-Boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in Children With HIV
• Recent EU Clinical Trials: A Study to Assess the Acceptability of the Darunavir/Cobicistat (DRV/COBI) Fixed-dose Combination (FDC) Tablet in Human Immunodeficiency Virus (HIV)-1 Infected Children Aged ≥3 Years and Weighing ≥15 kg to <25 kg
• Description: Darunavir is the latest weapon in the arsenal of agents to combat human immunodeficiency virus type 1(HIV-1). As an HIV-1 protease inhibitor, its mechanism of action involves blocking the cleavage of the gag and gag–pol polyproteins into functional proteins essential for the production of infectious progeny virus; the result is the production of immature, noninfectious viral particles. Compared to predecessor HIV protease inhibitors, darunavir retains activity against resistant stains, a critical factor with the continual emergence of multidrug- resistant (MDR) mutants. Despite experiencing a 13-fold reduction in binding to MDR HIV-1 protease, this binding is 1.5 orders of magnitude tighter than the first-generation protease inhibitors. Furthermore, darunavir exhibits less than a 10-fold decrease in susceptibility in cell culture against 90% of 3309 clinical isolates resistant to amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir. In contrast, darunavir-resistant viruses display limited susceptibility to only tipranavir, suggesting limited cross-resistance between these two protease inhibitors. To avoid the issues of the peptide-based protease inhibitors, darunavir has evolved from a structure-based design effort to minimize peptidic features and reduce molecular weight and complexity.
• Uses: Second generation HIV-1-protease inhibitor; structurally similar to amprenavir. Antiviral
• Clinical Use: Treatment of HIV infection (in combination with other antiretroviral drugs)
• Drug interactions: Potentially hazardous interactions with other drugsAntibacterials: rifabutin concentration increased - reduce dose of rifabutin; darunavir concentration reduced by rifampicin - avoid.Anticoagulants: avoid with apixaban and rivaroxabanAntidepressants: possibly reduced concentration of paroxetine and sertraline; darunavir concentration reduced by St John’s wort - avoid.Antimalarials: concentration of lumefantrine increased; possibly increases concentration of quinineAntipsychotics: possibly increases concentration of aripiprazole (reduce dose of aripiprazole); possibly increases quetiapine concentration - avoid.Antivirals: avoid with boceprevir or telaprevir; take didanosine 1 hour before or 2 hours after darunavir administration; concentration reduced by efavirenz - adjust dose; concentration of both drugs increased with indinavir and simeprevir - avoid with simeprevir; concentration reduced by lopinavir, also concentration of lopinavir increased - avoid; concentration of maraviroc increased, consider reducing dose of maraviroc; concentration of paritaprevir increased and paritaprevir reduces darunavir concentration; concentration reduced by saquinavir; increased risk of rash with raltegravir; avoid with telaprevir.Cytotoxics: possibly increases bosutinib concentration, avoid or reduce dose of bosutinib; possibly increases everolimus concentration - avoid; possibly increases ibrutinib concentration - reduce ibrutinib dose.Ergot alkaloids: increased risk of ergotism - avoid.Lipid-lowering drugs: possibly increased risk of myopathy with atorvastatin and rosuvastatin, reduce dose of rosuvastatin; possibly increases pravastatin concentration; avoid with lomitapide; avoid with simvastatin.1Orlistat: absorption of darunavir possibly reduced.Ranolazine: possibly increases ranolazine concentration - avoid.

Technology Process of Darunavir

There total 129 articles about Darunavir 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: 95.0%

(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-{(1S,2R)-2-hydroxy-3-[(2-methylpropyl)-4-nitrophenylsulfonylamino]-1-phenylmethylpropyl}carbamate (799241-76-2) → darunavir (206361-99-1)

Guidance literature:

With palladium 10% on activated carbon; hydrogen; In methanol; at 20 ℃; for 24h;

DOI:10.1002/ejoc.201600062

Reference yield: 94.0%

1-[[[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl]oxy]pyrrolidine-2,5-dione (253265-97-3) + 4-amino-N-(2R,3S)(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide (169280-56-2) → darunavir (206361-99-1)

Guidance literature:

In dimethyl sulfoxide; at 15 - 30 ℃; Solvent;

DOI:10.1007/s11164-019-03948-4

Reference yield: 92.0%

[(1S,2R)-2-hydroxy-3-[(2-methylpropyl)amino]-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester (664344-42-7) + 4-aminobenzenesulfonyl chloride (24939-24-0) → darunavir (206361-99-1)

Guidance literature:

With sodium hydrogencarbonate; In dichloromethane; water; at 20 - 35 ℃; for 4h;

upstream raw materials:

1-[[[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl]oxy]pyrrolidine-2,5-dione

4-amino-N-(2R,3S)(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide

(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol

βS--αR-<<(2-methylpropyl)amino>methyl>-benzenepropanol

Refernces

• 1、 Girigani, Sathyanarayana,Singh, Harnam,Kola, Sankar Rao,Dayanand Yelmeli, Vijayalaxmi,Regula, Venu Gopal,Shah, Sakshi,Jain, Neelu,Kumar, Pramod. "An improved and robust scale-up process aided with identification and control of critical process impurities in darunavir ethanolate". . p. 267 - 281. Retrieved 2019/08/26.
• 2、 -. "A NOVEL PROCESS FOR THE PREPARATION OF HIV PROTEASE INHIBITOR AND INTERMEDIATES THEREOF". . . Retrieved 2018/02/16.