Ritonavir

Base Information

• Chemical Name: Ritonavir
• CAS No.: 155213-67-5
• Molecular Formula: C37H48N6O5S2
• Molecular Weight: 720.957
• Hs Code.: 29341000
• Mol file: 155213-67-5.mol

Synonyms:2,4,7,12-Tetraazatridecan-13-oicacid,10-hydroxy-2-methyl-5-(1-methylethyl)-1-[2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-,5-thiazolylmethyl ester, (5S,8S,10S,11S)- (9CI);A 84538;ABT 538;Abbott84538;NSC 693184;Norvir;

Chemical Property of Ritonavir

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 120-122°C
• Refractive Index: 1.599
• Boiling Point: 947 °C at 760 mmHg
• PKA: 11.47±0.46(Predicted)
• Flash Point: 526.6 °C
• PSA: 202.26000
• Density: 1.239 g/cm³
• LogP: 7.07790
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: soluble10mg/mL (clear solution, warmed)
• Water Solubility.: 5mg/L(ms)

Purity/Quality:

99%, ^*data from raw suppliers

Ritonavir ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi,Xn
• Hazard Codes: Xi,Xn
• Statements: 36/38-20/21/22-41
• Safety Statements: 26-37/39-36/37-39

MSDS Files:

SDS file from LookChem

Useful:

• Description: Ritonavir (brand name: Norvir) was launched in Germany, the UK and US for treatment of advanced HIV in combination with antiretroviral nucleoside analogs in a record 72 days by the FDA. It is an inhibitor of HIV aspartic protease which is critical in the processing of a propeptide into the gag, gag-pol gene products and the protease itself. This inhibition results in the release of non-infectous immature virus particles. It is greater than 500-fold more selective for viral aspartic protease than the human version, has good oral bioavailability and may increase the bioavailability of other protease inhibitors. Ritonavir was able to increase the CD4 and CD8 lymphocyte count as well as reduce viral RNA. It is more potent than saqunavir and comparible in potency to zidovudine and lamivudine.
• Uses: Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1-infected patients. Ritonivir is an HIV protease inhibitor (EC50 = 25 nM) that also inhibits CYP3A4, the primary cytochrome P450 isoform that metabolizes protease inhibitors. Through CYP3A4 inhibition, low doses of ritonivir can reduce the metabolism of concomitantly administered protease inhibitiors, enhancing their bioavailability and efficacy.
• Indications: Ritonavir is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults and children older than 1 month. Although Ritonavir is a potent inhibitor of HIV-1 and HIV-2 protease, it is not well tolerated in higher doses. It is mainly used in low doses to increase blood levels of other protease inhibitors and to extend their dosing interval. Ritonavir is more commonly associated with gastrointestinal side effects, altered taste sensation, paresthesias, and hypertriglyceridemia than are other protease inhibitors. Pancreatitis may occur in the presence or absence of hypertriglyceridemia.
• Drug interactions: Ritonavir-boosted nirmatrelvir has significant drug-drug interactions, primarily due to the ritonavir component of the combination. Boosting with ritonavir, which is a strong CYP3A inhibitor and a P-glycoprotein inhibitor, is required to increase the exposure of nirmatrelvir to a concentration that is effective against SARS-CoV-2. However, it may also increase concentrations of certain concomitant medications, thereby increasing the potential for serious and sometimes life-threatening drug toxicities. Additionally, ritonavir is an inhibitor, inducer, and substrate of various other drug-metabolizing enzymes and/or drug transporters.

Technology Process of Ritonavir

There total 19 articles about Ritonavir 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: 91.5%

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine (154212-61-0) + (2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane (144164-11-4) → ritonavir (155213-67-5)

Guidance literature:

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine; With N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide; at 27 ℃; for 0.5h;

(2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane; for 7h; Temperature;

Reference yield: 85.29%

N-ritonavir (176655-55-3) + ((5-thiazolyl)methyl)-(4-nitrophenyl)carbonate (144163-97-3) → ritonavir (155213-67-5)

Guidance literature:

With sodium hydrogencarbonate; In ethyl acetate; at 50 - 60 ℃; for 9h;

Reference yield: 79.0%

C37H53N5O5S + (5-thiazolyl)methyl 2,2,2-trichloroethanol carbonate → ritonavir (155213-67-5)

Guidance literature:

C₃₇H₅₃N₅O₅S; With hydrogenchloride; In water; ethyl acetate; at 0 - 20 ℃; for 6h; Green chemistry;

(5-thiazolyl)methyl 2,2,2-trichloroethanol carbonate; With triethylamine; In ethyl acetate; at 0 - 20 ℃; for 12h; Green chemistry;

upstream raw materials:

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine

(2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane

L-valine methylester hydrochloride

((5-thiazolyl)methyl)-(4-nitrophenyl)carbonate

Downstream raw materials:

(2S)-N-(((1S)-1-benzyl-2-((4S,5S)-4-benzyl-2-oxo-1,3-oxazolidin-5-yl)ethyl)-2-((((2-isopropyl-1,3-thiazol-4-yl)methyl)N-methyl-amino)carbonyl)amino)-3-methylbutanamide

(2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane

N-ritonavir

Refernces

• 1、 -. "Novel method for synthesizing ritonavir". Paragraph 0025-0026. . Retrieved 2020/09/20.
• 2、 -. "Preparation method of ritonavir". . . Retrieved 2018/07/30.