Lopinavir

Base Information

• Chemical Name: Lopinavir
• CAS No.: 192725-17-0
• Molecular Formula: C37H48N4O5
• Molecular Weight: 628.812
• Hs Code.: 29335990
• European Community (EC) Number: 844-598-9
• UNII: 2494G1JF75
• DSSTox Substance ID: DTXSID8046456
• Nikkaji Number: J1.543.461I
• Wikipedia: Lopinavir
• Wikidata: Q422585
• NCI Thesaurus Code: C2095
• RXCUI: 195088
• Pharos Ligand ID: HKBAZ6KMX2M4
• Metabolomics Workbench ID: 43588
• ChEMBL ID: CHEMBL729
• Mol file: 192725-17-0.mol

Synonyms:A 157378.0;A-157378.0;A157378.0;ABT 378;ABT-378;ABT378;lopinavir;N-(4-(((2,6-dimethylphenoxy)acetyl)amino)-3-hydroxy-5-phenyl-1-(phenylmethyl)pentyl)tetrahydro-alpha-(1-methylethyl)-2-oxo-1(2H)-pydrimidineacetamide

Chemical Property of Lopinavir

Chemical Property:

• Appearance/Colour: white crystalline solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 124-127 °C
• Refractive Index: 1.577
• Boiling Point: 924.1 °C at 760 mmHg
• PKA: 13.89±0.46(Predicted)
• Flash Point: 512.7 °C
• PSA: 120.00000
• Density: 1.163 g/cm³
• LogP: 4.39310
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility.: DMSO: soluble20mg/mL, clear
• XLogP3: 5.9
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 15
• Exact Mass: 628.36247064
• Heavy Atom Count: 46
• Complexity: 940

Purity/Quality:

99%min, ^*data from raw suppliers

Lopinavir ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: CC1=C(C(=CC=C1)C)OCC(=O)NC(CC2=CC=CC=C2)C(CC(CC3=CC=CC=C3)NC(=O)C(C(C)C)N4CCCNC4=O)O
• Isomeric SMILES: CC1=C(C(=CC=C1)C)OCC(=O)N[C@@H](CC2=CC=CC=C2)[C@H](C[C@H](CC3=CC=CC=C3)NC(=O)[C@H](C(C)C)N4CCCNC4=O)O
• Recent ClinicalTrials: AB1 in Adult Patients With Sickle Cell Disease (SCD)
• Recent EU Clinical Trials: A Pilot study platform to investigate the pharmacodynamics on QT‐prolongation and pharmacokinetics after multiple dose administration of potential combination treatments for COVID-19 in healthy volunteers
• Description: Lopinavir, the sixth HIV protease inhibitor in the “navir” class, was launched in coformulation with ritonavir, another HIV protease inhibitor already marketed (Abbott, 1996); this original formulation was introduced as Kaletra for use in combination with either nucleoside or non-nucleoside reverse transcriptase inhibitors for the treatment of AIDS in adults and children. Lopinavir is a peptidomimetic compound with a structural core identical to that of ritonavir, on which terminal groups, particularly a modified valine, were introduced by peptide coupling procedures. Lopinavir is a potent competitive inhibitor of HIV-I protease exhibiting high potential against ritonavir-resistant mutations. In several animal species, pharmacokinetic studies with the lopinavirlritonavir association showed that the modest properties of lopinavir were significantly improved in presence of ritonavir, in terms of Cmax and duration of action. Ritonavir inhibits the P450 isoenzyme CYP3A4 and the human liver microsomal metabolism of lopinavir, so strongly amplifying plasma levels of this latter component. In AIDS patients, the plasma HIV RNA level was considerably reduced and the CD4+ T-cell counts increased after administration of lopinavir combined with relatively small doses of ritonavir. Kaletra is intended to be used jointly with other antiretroviral agents.
• Uses: Lopinavir has been used as a ZMPSTE24 and human immunodeficiency virus protease inhibitor. A selective HIV protease inhibitor. An analogue of Ritonavir. Antiviral. Lopinavir is a potent HIV protease inhibitor with Ki of 1.3 pM
• Indications: Lopinavir is available in the United States only as a fixed-dose combination with ritonavir (Kaletra). In this regimen, a low dose of ritonavir is used to inhibit the rapid inactivation of lopinavir by CYP3A4.
• Therapeutic Function: Antiviral
• Clinical Use: Treatment of HIV infection (in combination with ritonavir and other antiretroviral agents)
• Drug interactions: Potentially hazardous interactions with other drugs In combination with ritonavir - see ritonavir interactions. Anti-arrhythmics: increased risk of ventricular arrhythmias with flecainide - avoid; possibly increased lidocaine concentration. Antibacterials: concentration reduced by rifampicin - avoid; concentration of delamanid increased; avoid with telithromycin in severe renal and hepatic impairment; AUC of bedaquiline increased by 22%, avoid. Anticoagulants: avoid with apixaban and rivaroxaban. Antidepressants: concentration reduced by St John’s wort - avoid. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenytoin, primidone and phenobarbital. Antimalarials: use artemether/lumefantrine with caution. Antipsychotics: possibly inhibits metabolism of aripiprazole - reduce dose of aripiprazole; possibly increases quetiapine concentration - avoid. Antivirals: avoid with boceprevir, daclatasvir and telaprevir; concentration of darunavir and fosamprenavir reduced - avoid; in combination with ritonavir concentration of elvitegravir increased - reduce dose of elvitegravir; concentration reduced by efavirenz, tipranavir and possibly nevirapine, consider increasing lopinavir dose; concentration of paritaprevir increased - avoid; increased risk of ventricular arrhythmias with saquinavir - avoid; concentration of tenofovir increased; concentration of maraviroc increased, consider reducing maraviroc dose. Bosentan: concentration of bosentan increased, consider reducing bosentan dose. Ciclosporin: may increase concentration of ciclosporin. Cytotoxics: reduce dose of ruxolitinib. Lipid lowering agents: increased risk of myopathy with atorvastatin; possibly increased risk of myopathy with rosuvastatin (reduce rosuvastatin dose) and simvastatin - avoid; avoid with lomitapide. Orlistat: absorption of lopinavir possibly reduced. Ranolazine: possibly increases ranolazine concentration - avoid. Sirolimus: may increase concentration of sirolimus. Tacrolimus: may increase concentration of tacrolimus.

Technology Process of Lopinavir

There total 39 articles about Lopinavir 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: 97.0%

(2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl)amino-1,6-diphenylhexane (S)-pyroglutamic acid salt (192726-06-0) + C13H14N2O2 → lopinavir (192725-17-0,1798014-18-2)

Guidance literature:

In ethyl acetate; at 25 ℃; for 8h; Solvent;

Reference yield: 96.0%

N-(2,6-dimethyl-phenyloxy acetyloxy)succinimide (224648-11-7) + C28H40N4O2*C5H7NO3 → lopinavir (192725-17-0,1798014-18-2)

Guidance literature:

With triethylamine; In N,N-dimethyl-formamide; at 25 ℃; for 8h; Solvent;

Reference yield: 96.0%

(2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl)amino-1,6-diphenylhexane (S)-pyroglutamic acid salt (192726-06-0) + N-(2,6-dimethyl-phenyloxy acetyloxy)succinimide (224648-11-7) → lopinavir (192725-17-0,1798014-18-2)

Guidance literature:

With triethylamine; In N,N-dimethyl-formamide; at 25 ℃; for 8h; Solvent;

upstream raw materials:

(2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-amino-1,6-diphenylhexane

(S)-tetrahydro-α-(1-methylethyl)-2-oxo-1(2H)-pyrimidineacetic acid

(S)-2-(3-Amino-propylamino)-3-methyl-butyric acid methyl ester

(S)-3-Methyl-2-(2-oxo-tetrahydro-pyrimidin-1-yl)-butyric acid methyl ester

Downstream raw materials:

(2S)-N-{(1S,3S,4S)-1-benzyl-4-{[(2,6-dimethylphenoxy)acetyl]amino}-3-[(methylthio)methoxy]-5-phenylpentyl}-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanamide

Refernces

• 1、 Reddy, Peketi Rajesh,Musunuri, Sivanadh,Ramasekhara Reddy,Subrahmanyam Chittala,Murthy,Krishnamohan. "Synthesis and characterization of novel analogues of lopinavir". . p. 151 - 158. Retrieved 2021/01/06.
• 2、 -. "Preparation of lopinavir by one-pot method". . . Retrieved 2020/04/02.