Saquinavir

Base Information

• Chemical Name: Saquinavir
• CAS No.: 127779-20-8
• Deprecated CAS: 131176-13-1
• Molecular Formula: C₃₈H₅₀N₆O₅
• Molecular Weight: 670.852
• UNII: L3JE09KZ2F
• DSSTox Substance ID: DTXSID6044012
• Nikkaji Number: J378.898I
• Wikipedia: Saquinavir
• Wikidata: Q422654
• NCI Thesaurus Code: C29444
• RXCUI: 83395
• Pharos Ligand ID: 6XR2TLCRM53T
• Metabolomics Workbench ID: 52674
• ChEMBL ID: CHEMBL114
• Mol file: 127779-20-8.mol

Synonyms:Invirase;Monomethanesulfonate, Saquinavir;Ro 31 8959;Ro 31-8959;Ro 318959;Saquinavir;Saquinavir Mesylate;Saquinavir Monomethanesulfonate;Saquinivir

Chemical Property of Saquinavir

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 91.5oC
• Refractive Index: 1.598
• Boiling Point: 1015 °C at 760 mmHg
• PKA: 11.05±0.46(Predicted)
• Flash Point: 567.7 °C
• PSA: 166.75000
• Density: 1.211 g/cm³
• LogP: 4.90330
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Water Solubility.: 35.8mg/L(25 oC)
• XLogP3: 4.2
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 13
• Exact Mass: 670.38426872
• Heavy Atom Count: 49
• Complexity: 1140

Purity/Quality:

99% ^*data from raw suppliers

Saquinavir ^*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)(C)NC(=O)C1CC2CCCCC2CN1CC(C(CC3=CC=CC=C3)NC(=O)C(CC(=O)N)NC(=O)C4=NC5=CC=CC=C5C=C4)O
• Isomeric SMILES: CC(C)(C)NC(=O)[C@@H]1C[C@@H]2CCCC[C@@H]2CN1C[C@H]([C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(=O)N)NC(=O)C4=NC5=CC=CC=C5C=C4)O
• Recent ClinicalTrials: The Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year
• Recent EU Clinical Trials: Raltegravir-based regimen versus raltegravir-based regimen plus atorvastatin for reducing ?inflamaging? (aging-related complication) in HIV-infected patients older than 60 years.
• Recent NIPH Clinical Trials: Effect of a pharmaceutical excipient, cremophol EL on the plasma concentration-time profile of saquinavir and fexofenadine after their oral administrations at doses used in the exploratory investigational new drug clinical studies
• Description: Saquinavir mesylate, the first HIV protease inhibitor to reach the market, was launched in the U.S.A.. It is indicated for use in combination with approved nucleoside analogs for the treatment of advanced HIV infection. Saquinavir, a transition state analog of Phe-Pro, is a very potent and competitive inhibitor of HIV-1 and HIV-2 proteases with high specificity. Saquinavir inhibits the last stage in the replication process of HIV and prevents virion maturation in both acute and chronically infected cells. Combination of saquinavir with the nucleoside analogs such as zidovudine (AZT) or/and zalcitabine which inhibit the enzyme reverse transcriptase and target at an earlier stage in the HIV replication process, shows a greater than additive effect in increase in CD4 cell counts and reduction in viral load, with the combination delaying the onset of resistance to either drug alone. Saquinavir is well tolerated alone and in combination with A n .
• Uses: Antiviral (HIV protease inhibitor).
• Indications: Saquinavir is a potent inhibitor of HIV-1 and HIV-2 protease. Fortovase, a soft gel preparation of saquinavir, has largely replaced saquinavir mesylate capsules (Invirase) because it has improved bioavailability. Saquinavir is usually well tolerated and most frequently produces mild gastrointestinal side effects.
• Clinical Use: Treatment of HIV infection (in combination with other antiretroviral drugs)
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: increased risk of ventricular arrhythmias with alfentanil, fentanyl and methadone - avoid. Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone, disopyramide, dronedarone, flecainide, lidocaine or propafenone - avoid. Antibacterials: increased risk of ventricular arrhythmias with clarithromycin, dapsone, erythromycin or moxifloxacin - avoid; increased risk of ventricular arrhythmias with delamanid; concentration of rifabutin increased; rifampicin and rifabutin can reduce saquinavir levels by 80% and 40% respectively (metabolism accelerated); increased hepatoxicity with rifampicin - avoid; concentration of both drugs increased with fusidic acid. Anticoagulants: avoid with apixaban and rivaroxaban. Antidepressants: increased risk of ventricular arrhythmias with trazodone or tricyclics - avoid; concentration reduced by St John’s wort - avoid. Antiepileptics: carbamazepine, phenobarbital, and phenytoin and possibly primidone can reduce saquinavir levels. Antifungals: concentration increased by ketoconazole - avoid. Antihistamines: increased risk of ventricular arrhythmias with mizolastine - avoid. Antimalarials: avoid with piperaquine with artenimol; use artemether/lumefantrine with caution; increased risk of ventricular arrhythmias with quinine - avoid. Antipsychotics: increased risk of ventricular arrhythmias with clozapine, haloperidol or phenothiazines - avoid; possibly increased risk of ventricular arrhythmias with pimozide and quetiapine - avoid; possibly inhibits aripiprazole metabolism - reduce aripiprazole dose; possibly increases lurasidone concentration - avoid. Antivirals: tipranavir and efavirenz can reduce saquinavir levels; increased risk of ventricular arrhythmias with atazanavir or lopinavir - avoid; concentration increased by indinavir and ritonavir; reduced darunavir concentration; concentration of maraviroc increased, consider reducing dose of maraviroc. Anxiolytics and hypnotics: midazolam concentration possibly increased (prolonged sedation) - avoid with oral midazolam. Beta-blockers: increased risk of ventricular arrhythmias with sotalol - avoid. Ciclosporin: concentration of both drugs increased. Cytotoxics: possibly increases concentration of axitinib, ibrutinib and panobinostat, reduce dose of axitinib, ibrutinib and panobinostat; possibly increases bosutinib, cabazitaxel, ceritinib and docetaxel concentration - avoid or consider reducing dose; possibly increases concentration of crizotinib and everolimus - avoid; avoid with lapatinib, olaparib and pazopanib; reduce dose of ruxolitinib. Dapoxetine: increased risk of toxicity - avoid. Domperidone: possibly increases risk of ventricular arrhythmias - avoid. Ergot alkaloids: risk of ergotism - avoid. Guanfacine: concentration possibly increased - halve guanfacine dose. Lipid-lowering drugs: increased risk of myopathy with rosuvastatin and simvastatin - avoid; possibly increased myopathy with atorvastatin; avoid with lomitapide. Naloxegol: possibly increases naloxegol concentration - avoid. Orlistat: absorption possibly reduced by orlistat. Pentamidine: increased risk of ventricular arrhythmias - avoid. Ranolazine: possibly increases ranolazine concentration - avoid.

Technology Process of Saquinavir

There total 77 articles about Saquinavir 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:

(2S)-2-[(quinoline-2-carbonyl)-amino]-succinamic acid (136465-98-0) + cis-N-butyldecahydro-2-<2(R)-hydroxy-4-phenyl-3(S)-aminobutyl>-(4aS,8aS)-isoquinoline-3(S)-carboxamide (136522-17-3) → Saquinavir (127779-20-8,128053-46-3,137622-85-6,147922-51-8,147922-52-9)

Guidance literature:

With 1-Hydroxy-2-pyridon; dicyclohexyl-carbodiimide; Yield given;

Reference yield:

(3S,4aS,8aS)-N-tert-butyl-decahydroisoquinoline-3-carboxamide (128019-40-9,149510-73-6,136465-81-1,168899-60-3) → Saquinavir (127779-20-8,128053-46-3,137622-85-6,147922-51-8,147922-52-9)

Guidance literature:

Multi-step reaction with 5 steps

1: dimethylformamide / 120 °C

2: 1.) MeNH₂, 2.) HCl

4: H₂ / Pd/C

With hydrogenchloride; hydrogen; methylamine; palladium on activated charcoal; In N,N-dimethyl-formamide;

Reference yield:

phthaloyl-L-phenylalanyl chloride (32150-91-7) → Saquinavir (127779-20-8,128053-46-3,137622-85-6,147922-51-8,147922-52-9)

Guidance literature:

Multi-step reaction with 11 steps

1: 2.) H₃O(+) / 1.) 90 deg C

3: NaBH₄

5: p-TsOH, EtOH

6: t-BuOK

7: dimethylformamide / 120 °C

8: 1.) MeNH₂, 2.) HCl

10: H₂ / Pd/C

With hydrogenchloride; sodium tetrahydroborate; ethanol; oxonium; potassium tert-butylate; hydrogen; toluene-4-sulfonic acid; methylamine; palladium on activated charcoal; In N,N-dimethyl-formamide;

upstream raw materials:

quinoline-2-carboxylic acid

2-[3(S)-[(L-asparaginyl)-amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamide

(2S)-2-[(quinoline-2-carbonyl)-amino]-succinamic acid

cis-N-butyldecahydro-2-<2(R)-hydroxy-4-phenyl-3(S)-aminobutyl>-(4aS,8aS)-isoquinoline-3(S)-carboxamide

Downstream raw materials:

invirase

Refernces

• 1、 -. "NOVEL POLYMORPHS OF SAQUINAVIR". Page/Page column 8-9. . Retrieved 2010/09/17.
• 2、 -. "Oral dosage forms of water insoluble drugs and methods of making the same". . . Retrieved 2008/06/13.