Amprenavir

Base Information

• Chemical Name: Amprenavir
• CAS No.: 161814-49-9
• Molecular Formula: C₂₅H₃₅N₃O₆S
• Molecular Weight: 505.635
• Hs Code.: 29350090
• European Community (EC) Number: 827-179-5
• UNII: 5S0W860XNR
• DSSTox Substance ID: DTXSID5046061
• Nikkaji Number: J1.015.291G
• Wikipedia: Amprenavir
• Wikidata: Q422198
• NCI Thesaurus Code: C28824
• RXCUI: 228656
• Pharos Ligand ID: XD1MZWF5LZW5
• Metabolomics Workbench ID: 43012
• ChEMBL ID: CHEMBL116
• Mol file: 161814-49-9.mol

Synonyms:(3S-(3R*(1R*,2S*)))-(3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-(phenylmethyl)propyl) tetrahydro-3-furanyl carbamate;Agenerase;amprenavir;tetrahydro-3-furyl N-(3-(4-amino-N-isobutylbenzenesulfonamido)-1-benzyl-2-hydroxypropyl)carbamate;Vertex VX478;VX 478;VX-478

Chemical Property of Amprenavir

Chemical Property:

• Appearance/Colour: off-white to pale yellow
• Melting Point: 72-74 °C
• Refractive Index: 1.61
• PKA: 11.54±0.46(Predicted)
• PSA: 139.57000
• Density: 1.3 g/cm³
• LogP: 4.45570
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: soluble20mg/mL, clear
• XLogP3: 2.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 12
• Exact Mass: 505.22465702
• Heavy Atom Count: 35
• Complexity: 745

Purity/Quality:

99.9% ^*data from raw suppliers

Amprenavir ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)CN(CC(C(CC1=CC=CC=C1)NC(=O)OC2CCOC2)O)S(=O)(=O)C3=CC=C(C=C3)N
• Isomeric SMILES: CC(C)CN(C[C@H]([C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CCOC2)O)S(=O)(=O)C3=CC=C(C=C3)N
• Recent ClinicalTrials: Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy
• Recent EU Clinical Trials: Strategic long term, immunologically driven treatment interruptions in previously naive patients starting HAART: a controlled, randomized, multicenter study
• Description: Amprenavir was launched as Agenerase in the US for the treatment of AIDS patients in combination with approved agent antiretroviral nucleoside analogs. It is the fifth non-peptidic inhibitor of HIV-1 protease to be marketed in this indication after the last approved Neflinavir. Amprenavir, designed via a structure-based process, is the smallest molecule in the 《navir》 class and exhibits a reduced peptidic character. An improved process for preparation comprising four steps from a (1S, 2R)-2-hydroxy-3-aminopropylcarbamate has been developed. Amprenavir is a potent inhibitor of HIV-1 aspartyl protease (Ki = 0.6nM), an enzyme required by the virus to cleave pro-form polyproteins to structural proteins during the last stage in the replication process. The compound displays good oral bioavailability in humans and penetrates the CNS, which is an important advantage in long-term treatment. Its plasma half-life is approximately 10h. Treatment with Amprenavir in combination with nucleoside analog reverse transcriptase inhibitors considerably decreases viral load and restores CD4+ T-cell counts in patients with HIV infection. Amprenavir is an inhibitor of HIV protease (Ki = 0.04 nM). It inhibits the cytopathic effects of HIV-1 in MT-4 cells (IC50 = 150 nM). Formulations containing amprenavir have been used in combination with other antiretroviral agents in the treatment of HIV-1 infection.
• Uses: A selective HIV protease inhibitor. An analogue of Ritonavir Protease inhibitor, anti-HIV agent
• Indications: Amprenavir (Agenerase) is administered twice daily, providing the patient with an advantage over other protease inhibitors that must be taken more frequently (e.g., indinavir, saquinavir). Common side effects of am-prenavir include nausea, vomiting, diarrhea, and perioral paraesthesias. Rash occurs in approximately 20 to 30% of patients and can be mild or severe (Stevens- Johnson syndrome).
• Therapeutic Function: Antiviral
• Clinical Use: Treatment of HIV infection (in combination with other antiretroviral drugs)

Technology Process of Amprenavir

There total 33 articles about Amprenavir 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: 90.0%

4-nitro-N-((2R(syn),3S)-2-hydroxy-4-phenyl-3-((S)-tetrahydrofuran-3-yloxycarbonylamino)-butyl)-N-isobutylbenzenesulfonamide (160231-69-6) → amprenavir (161814-49-9)

Guidance literature:

With tin(ll) chloride; In ethyl acetate; at 70 ℃; for 1h;

DOI:10.1021/ol016147s

Reference yield:

C25H33N3O8S → Amprenavir (858344-05-5,161814-49-9)

Guidance literature:

With hydrogen; palladium 10% on activated carbon; In ethyl acetate; at 20 ℃; for 14h;

Reference yield:

(2S)-2-[1'(S)-1-azido-2-phenylethyl]oxirane (136465-89-9) → amprenavir (161814-49-9)

Guidance literature:

Multi-step reaction with 4 steps

1: propan-2-ol / 12 h / 80 °C

2: aq. NaHCO₃

3: H₂ / 10percent Pd/C / ethyl acetate

4: Et₃N / CH₂Cl₂ / 12 h / 23 °C

With hydrogen; sodium hydrogencarbonate; triethylamine; palladium on activated charcoal; In dichloromethane; ethyl acetate; isopropyl alcohol;

DOI:10.1016/S0960-894X(98)00098-5

upstream raw materials:

1-({[(3S)-tetrahydro-3-furanyloxy]carbonyl}oxy)-2,5-pyrrolidinedione

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

4-nitro-N-((2R(syn),3S)-2-hydroxy-4-phenyl-3-((S)-tetrahydrofuran-3-yloxycarbonylamino)-butyl)-N-isobutylbenzenesulfonamide

(1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester

Refernces

• 1、 Gadakh, Sunita K.,Santhosh Reddy,Sudalai, Arumugam. "Enantioselective synthesis of HIV protease inhibitor amprenavir via Co-catalyzed HKR of 2-(1-azido-2-phenylethyl)oxirane". experimental part. p. 898 - 903. Retrieved 2012/09/22.
• 2、 -. "TREATMENT OF THE CNS EFFECTS OF HIV WITH VX-478, ALONE OR IN COMBINATION WITH AZT OR 3TC". Page/Page column 8. . Retrieved 2008/06/13.