ChemicalBook > CAS DataBase List > AMPRENAVIR

AMPRENAVIR

Product Name
AMPRENAVIR
CAS No.
161814-49-9
Chemical Name
AMPRENAVIR
Synonyms
VX 478;PROZEI;141W94;KVX-478;CS-1052;AGENERASE;AMPRENAVIR;Angenerase;AMPRENAVIR (VX-478);Amprenavir(KVX-478)
CBNumber
CB4186139
Molecular Formula
C25H35N3O6S
Formula Weight
505.63
MOL File
161814-49-9.mol
More
Less

AMPRENAVIR Property

Melting point:
72-74°C
Density 
1.30±0.1 g/cm3(Predicted)
storage temp. 
-20°C
solubility 
DMSO: soluble20mg/mL, clear
pka
11.54±0.46(Predicted)
form 
powder
color 
white to beige
optical activity
[α]/D +8 to +12°, c = 0.5 in methanol
InChIKey
YMARZQAQMVYCKC-OEMFJLHTSA-N
More
Less

Safety

RIDADR 
3077
WGK Germany 
3
HS Code 
29350090
Hazardous Substances Data
161814-49-9(Hazardous Substances Data)
More
Less

Hazard and Precautionary Statements (GHS)

More
Less

N-Bromosuccinimide Price

Sigma-Aldrich
Product number
SML0685
Product name
Amprenavir
Purity
≥98% (HPLC)
Packaging
5mg
Price
$100
Updated
2021/12/16
Sigma-Aldrich
Product number
SML0685
Product name
Amprenavir
Purity
≥98% (HPLC)
Packaging
25mg
Price
$404
Updated
2021/12/16
Cayman Chemical
Product number
15369
Product name
Amprenavir
Purity
≥95%
Packaging
25mg
Price
$319
Updated
2021/12/16
Cayman Chemical
Product number
15369
Product name
Amprenavir
Purity
≥95%
Packaging
5mg
Price
$75
Updated
2021/12/16
Cayman Chemical
Product number
15369
Product name
Amprenavir
Purity
≥95%
Packaging
50mg
Price
$600
Updated
2021/03/22
More
Less

AMPRENAVIR Chemical Properties,Usage,Production

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.

Description

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.

Chemical Properties

Off-White to Pale Yellow

Originator

Vertex Pharm (US)

Uses

A selective HIV protease inhibitor. An analogue of Ritonavir

Uses

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).

Manufacturing Process

(1-Oxiranyl-2-phenylethyl)-carbamic acid t-butyl ester may be synthesized from available starting materials (see B. E. Evans et al., J. Org. Chem., 50, p.4615 (1985)). The amprenavir may be preparated with the next steps.
1. (1-Benzyl-3-isobutylaminopropyl)-carbamic acid t-butylester. A solution of 4.1 g of epoxide (1-oxiranyl-2-phenylethyl)-carbamic acid t-butyl ester in 30 ml of ethanol was treated with 22.4 ml of isobutylamine and heated under reflux for 1 h. The mixture was concentrated to yield the title compound as a white solid which was used without subsequent purification.
2. To a solution of the above compound (2.5 g, 7.43 mmol) in CH2Cl2 (50 ml) was added triethylamine (2.1 ml, 14.9 mmol) followed by addition of benzyl chloroformate (1.2 ml, 8.1 mmol). The mixture was allowed to stir at ambient temperature for 6 h. The solution was diluted with 1 L of CH2Cl2 and washed with water. The organics were dried over anhydrous MgSO4, concentrated under reduced pressure, then purified via silica gel chromatography. Gradient solvent system: CH2Cl2 followed by 3:97 methanol/CH2Cl2. (3-t- Butoxycabonylamino-4-phenylbutyl)-isobutylcarbamic acid benzyl ester (2.97 g) was obtained as a colorless oil. TLC: Rf= 0.14, 3:97 methanol/CH2Cl2. 3. BOC - protecting group was removed as followed: to a solution of 1.5 g (3.187 mmol) of the above compound of in ethyl acetate (25 ml) at - 20°C was bubbled anhydrous HCl gas for 10 min. The ice bath was removed and after an additional 15 min the reaction mixture was sparged with nitrogen, then concentrated in vacuo to provide 1.29 g of deprotected product as a white solid which was used directly for the next reaction TLC: Rf= 0.14, 10% methanol/CH2Cl2.
4. Isobutyl[4-phenyl-(S)-3-tetrahydrofuran-3-yl-oxycarbonylamino)-butyl]- carbamic acid benzyl ester. To a solution of 1.077 g of the above resultant crude compound (2.647 mmol) in acetonitrile (10 ml) was added sequentially at ambient temperature under an atmosphere of nitrogen, 1.61 ml (9.263 mmol) of diisopropylethylamine and 910 mg (3.97 mmol) of the Nsuccinimidyl-( S)-3-tetrahydrocfuryl carbonate. The last one was prepared from phosgene and (S)-(+)-3-hydroxytetrahydrofuran by usual procedure. After stirring for 3 h, an additional 223 mg (0.973 mmol) of the N-succinimidyl-(S)- 3-tetrahydrocfuryl carbonate was added. The mixture was stirred for 16 h and then concentrated in vacuo. The residue was taken up in ethyl acetate and washed with water, 0.5 N HCl, saturated sodium bicarbonate, saturated brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by low pressure silica gel column chromatography using a gradient 10% to 25% ethyl acetate in CH2Cl2 eluent to yield 1.025 g of the title product as a white solid. TLC: Rf= 0.10, 10% ethyl acetate/CH2Cl2.
5. A solution of 872 mg (1.799 mmol) isobutyl[4-phenyl-(S)-3- tetrahydrofuran-3-yl-oxycarbonylamino)-butyl]-carbamic acid benzyl ester in (10 ml) of ethyl alcohol was added, at ambient temperature under a nitrogen atmosphere, to a slurry of 87 mg (10% by weight) of 10% palladium on carbon in (5 ml) ethyl alcohol and hydrogenated for 16 h under a slight positive pressure of hydrogen. The mixture was filtered and concentrated in vacuo to yield 553.2 mg of the carbamic acid as a colorless glass which was used directly for ensuing reaction. TLC: Rf = 0.46, 10% methanol/CH2Cl2.
6. A solution of 102 mg of the resultant compound of a step 5 in 4:1 CH2Cl2/saturated aqueous NaHCO3 was treated sequentially, at ambient temperature under an atmosphere of nitrogen, with 65 mg of pnitrobenzenesulfonyl chloride and 51 mg of sodium bicarbonate. The mixture was stirred for 14 h, diluted with CH2Cl2, washed with saturated NaCl, then dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by low pressure silica gel chromatography using 20% diethyl ether/CH2Cl2 as eluent to provide 124 mg of the 1-benzyl-3-[isobutyl-(4- nitrobenzenesylfonyl)-amino]-propylcarbamic acid tetrahydrofuran-3(S)-yl] ester as a white solid. TLC: Rf = 0.36, 20% diethyl ether/CH2Cl2, HPLC: Rt = 15.15 min. (1H)-NMR (CDCl3) consist with structure.
7. A solution of 124 mg of the resultant compound of the step 6 in ethyl acetate was treated, at ambient temperature, with 13 mg of 10% palladium on carbon. The mixture was stirred for 14 h under an atmosphere of hydrogen, filtered through a pad of celite filter agent, and concentrated in vacuo. The residue was subjected to preparative HPLC to yield 82 mg of the ((1S,2R)-3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1- (phenylmethyl)propyl)-, (3S)-tetrahydro-3-furanyl carbamic ester a white solid. TLC: Rf= 0.10, 20% ether/CH2Cl2, HPLC: Rt= 13.16 min. (1H)-NMR (CDCl3) consistent with structure.

brand name

Agenerase (GlaxoSmithKline).

Therapeutic Function

Antiviral

Acquired resistance

Mutations at position 50, 76 and 84 of the protease enzyme gene are associated with significantly reduced susceptibility.

General Description

Amprenavir is a second-generation drug derived from hydroxyethylamine sulfonamide.

Pharmaceutical Applications

A synthetic compound formulated as the calcium salt of the oral prodrug fosamprenavir.

Biochem/physiol Actions

Protease inhibition results in inactive and immature virus.

Pharmacokinetics

Oral absorption: Not known/available
Cmax 700 mg + ritonavir 100 mg:c. 6.08 mg/L
twice daily
Cmin 700 mg + ritonavir 100 mg:c. 2.12 mg/L
twice daily
Plasma half-life: c. 7.7 h
Volume of distribution: c. 430 L
Plasma protein binding: c. 90%
Absorption
Fosamprenavir is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate by cellular phosphatases in the gut epithelium as it is absorbed. Absolute bioavailability has not been established. It can be taken without regard to food.
Distribution
It penetrates moderately well into the CNS. The semen:plasma ratio is negligible. It is not known if it is distributed into breast milk.
Metabolism and excretion
It is extensively metabolized by the cytochrome P450 (CYP) 3A4 enzyme system. Two major metabolites have been identified that appear to result from the oxidation of the tetrahydrofuran and aniline moieties. Around 14% of a dose is eliminated in the urine and 75% in feces, <3% as unchanged drug. Metabolites account for >90% of administered drug found in fecal samples. It should be used with caution and at reduced doses in adults with mild or moderate hepatic impairment; it is contraindicated in patients with severe hepatic impairment.

Clinical Use

Treatment of HIV infection (in combination with other antiretroviral drugs)

Side effects

The most common adverse events in patients receiving boosted fosamprenavir were diarrhea, nausea, headache, fatigue, vomiting and rash. Ritonavir-boosted fosamprenavir is associated with a dyslipidemia profile characteristic of those treated with other protease inhibitors boosted with 200 mg of ritonavir.

AMPRENAVIR Preparation Products And Raw materials

Raw materials

Preparation Products

More
Less

AMPRENAVIR Suppliers

Shanghai Boyle Chemical Co., Ltd.
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2926
Advantage
55
J & K SCIENTIFIC LTD.
Tel
010-82848833- ;010-82848833-
Fax
86-10-82849933
Email
jkinfo@jkchemical.com;market6@jkchemical.com
Country
China
ProdList
96815
Advantage
76
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel
821-50328103-801
Fax
86-21-50328109
Email
3bsc@sina.com
Country
China
ProdList
15877
Advantage
69
Alabiochem Tech.Co., Ltd.
Tel
0512-58900862;0512-56727736
Fax
0086-512-56765862
Email
sales@alabiochem.com;sales@alabiochem.com
Country
China
ProdList
1005
Advantage
59
Chembest Research Laboratories Limited
Tel
021-20908456-
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
5947
Advantage
61
Capot Chemical Co., Ltd
Tel
+86 (0) 571 85 58 67 18
Fax
0086-571-85864795
Email
sales@capotchem.com
Country
China
ProdList
18227
Advantage
66
Shanghai Scientia Pharmaceutical Technology Co., Ltd.
Tel
21-54301573- ;21-61721573-
Fax
(86)21-51861981
Email
sales@scientiapharm.com;scientiapharm@gmail.com
Country
China
ProdList
254
Advantage
62
JinYan Chemicals(ShangHai) Co.,Ltd.
Tel
13817811078;021-50426030
Fax
86-021-50426522,50426273
Email
sales@jingyan-chemical.com
Country
China
ProdList
10006
Advantage
60
Chemsky(shanghai)International Co.,Ltd.
Tel
021-50135380
Email
shchemsky@sina.com
Country
China
ProdList
32358
Advantage
50
China DongFan Chemical Co.,LTD
Tel
86-0571-85151182
Fax
86-0571-85151182
Email
sales@dongfan-chem.com
Country
China
ProdList
5702
Advantage
66
Jinan Trio PharmaTech Co., Ltd.
Tel
+86 (531) 88811783;
Fax
+86 (531) 55696010 QQ 1762738062
Email
sales@trio-pharmatech.com (International market);trio@trio-pharmatech.com(Domestic market)
Country
China
ProdList
1856
Advantage
62
Shanghai Sunway Pharmaceutical Technology Co., Ltd
Tel
Fax
021 51613951
Email
vivian.zhu@3wpharm.com
Country
China
ProdList
9879
Advantage
57
Dalian Meilun Biotech Co., Ltd.
Tel
0411-62910999- ;0411-62910999-
Email
sales@meilune.com;sales@meilune.com
Country
China
ProdList
3754
Advantage
58
T&W GROUP
Tel
021-61551611-
Fax
+86 21-50676805
Email
contact@trustwe.com
Country
China
ProdList
9758
Advantage
58
Hangzhou Sage Chemical Co., Ltd.
Tel
0571-86818502
Fax
Pls mail us for more information!
Email
info@sagechem.com
Country
China
ProdList
10277
Advantage
58
Suzhou Sibian Chemical Technology Co.,Ltd.
Tel
0512-65617459 18915409046
Fax
0512-65617459
Email
sales@sibian-chem.com
Country
China
ProdList
1930
Advantage
55
Beijing HuaMeiHuLiBiological Chemical
Tel
010-56205725;010-86181995
Fax
010-65763397
Email
waley188@sohu.com
Country
China
ProdList
12341
Advantage
58
NCE Biomedical Co.,Ltd.
Tel
4000-027-021 |24 hour enquiry :+86-13986109188 |English:+86-15623472865 |Japanese:+81-08033611988
Fax
+86-27-87599188
Email
sales@ncebiomed.com
Country
China
ProdList
1496
Advantage
55
Shanghai T&W Pharmaceutical Co., Ltd.
Tel
+86 21 61551611
Fax
+86 21 50676805
Country
China
ProdList
9914
Advantage
58
Nanjing Norris-Pharm Technology Co., Ltd
Tel
25-66112885-
Fax
+86-25-52131256
Email
sales@norris-pharm.com
Country
China
ProdList
9914
Advantage
55
Haoyuan Chemexpress Co., Ltd.
Tel
86-21-58998985
Fax
(86) 21-58955996
Email
apisales@chemexpress.com.cn
Country
China
ProdList
7557
Advantage
61
Shanghai Aladdin Bio-Chem Technology Co.,LTD
Tel
400-62063333-1
Fax
021-50323701
Email
market@aladdin-e.com
Country
China
ProdList
24980
Advantage
65
China Nobel Chem Co., Limited
Tel
+86(0)21 60484900
Fax
+86(0)21 60484900
Email
sales@nobelchem.com
Country
China
ProdList
765
Advantage
50
Shanghai TaoShu Biochemical Technology Co., Ltd.
Tel
021-33632979-
Fax
021-33632979
Email
service1@targetmol.com
Country
China
ProdList
7962
Advantage
58
Shanghai JONLN Reagent Co., Ltd.
Tel
400-0066400;021-60496031
Fax
021-55660885
Email
422131432@qq.com;422131432@qq.com
Country
China
ProdList
9998
Advantage
55
Bide Pharmatech Ltd.
Tel
021-61629020-8031;
Fax
+86-21-61629029
Email
sales@bldpharm.com;product07@bidepharm.com
Country
China
ProdList
44285
Advantage
60
HangZhou YuHao Chemical Technology Co., Ltd.
Tel
0571-82693216-
Fax
0571-82880190
Email
info@yuhaochemical.com
Country
China
ProdList
1853
Advantage
58
Wuhan Dahua Pharmaceutical Co., Ltd.
Tel
027-59262863 13277907145 QQ:3091977954
Fax
027-59420980
Email
dh.luna@whdhwy.com
Country
China
ProdList
4957
Advantage
58
Shanghai HuanChuan Industry Co.,Ltd.
Tel
021-61478794
Fax
021-61478794
Email
sales@hcshhai.com
Country
China
ProdList
9804
Advantage
50
AdooQ Bioscience CHINA
Tel
025-58849295
Fax
025-68650336
Email
info@adooq.cn
Country
China
ProdList
3007
Advantage
60
Hubei Jusheng Technology Co.,Ltd
Tel
027-59599241- ;027-59599240-
Fax
027-59599241
Email
1400878000@qq.com;1400868000@qq.com
Country
China
ProdList
9842
Advantage
58
LETOPHARM LIMITED
Tel
+86-21-5821 5861
Fax
+86-21-5106 2861
Email
sales@letopharm.com
Country
China
ProdList
2388
Advantage
58
Sigma-Aldrich
Tel
021-61415566- ;
Email
orderCN@merckgroup.com;orderCN@merckgroup.com
Country
China
ProdList
50837
Advantage
80
Shanghai Lollane Biological Technology Co.,Ltd.
Tel
021-52996696
Fax
+86-21-52996696
Email
2311958233@qq.com
Country
China
ProdList
3150
Advantage
55
AN PharmaTech Co Ltd
Tel
86(21)68097365
Fax
86(21)33321566
Email
sales@anpharma.net
Country
China
ProdList
4907
Advantage
55
Codow Chemical Co.,Ltd.
Tel
1862-009-9427
Fax
+86-20-62619665
Email
amy@howeipharm.com
Country
China
ProdList
18949
Advantage
55
Pharmacodia (Beijing) Co.,Ltd
Tel
+86-400-851-9921;+86-10-82826195
Fax
+86-10-82826195
Email
sales@pharmacodia.com
Country
China
ProdList
2320
Advantage
55
Shanghai EFE Biological Technology Co., Ltd.
Tel
021-65675885
Fax
021-65675885
Email
info@efebio.com
Country
China
ProdList
9918
Advantage
58
Guangzhou QiYun Biotechnology Co., Ltd.
Tel
020-61288194 61288195
Fax
020-61288700
Email
505721671@qq.com
Country
China
ProdList
3872
Advantage
58
Shanghai YuanYe Biotechnology Co., Ltd.
Tel
021-61312824-
Fax
QQ:3008007432
Email
3008007432@qq.com
Country
China
ProdList
30311
Advantage
60
Chengdu Dianchun Technology Co., Ltd
Tel
400-1196-196;028-84555506- ;028-84555506-
Fax
QQ:800101999
Email
cdhxsj@163.com;cdhxsj@163.com;cdhxsj@163.com
Country
China
ProdList
14604
Advantage
60
ShangHai Biochempartner Co.,Ltd
Tel
137-20134139-
Fax
QQ:2853530911
Email
candy@biochempartner.com
Country
China
ProdList
8060
Advantage
62
Amadis Chemical Company Limited
Tel
0086-571-89925085
Fax
0086-571-89925065
Email
sales@amadischem.com
Country
China
ProdList
132148
Advantage
58
Beijing Jin Ming Biotechnology Co., Ltd.
Tel
010-60605840-
Fax
010-60605840
Email
psaitong@jm-bio.com
Country
China
ProdList
12313
Advantage
58
Shenzhen SUNGENING Bio-Medical Co., Ltd.
Tel
0755-28967200-8056;0755-28967200-8062
Fax
0755-28967200
Email
hnsale203@sungening.com;wxf@sungening.com
Country
China
ProdList
9606
Advantage
60
Alpha Biopharmaceuticals Co., Ltd
Tel
0086-411-39042497
Fax
0086-411-39042693
Email
sales@alphabiopharm.com
Country
China
ProdList
896
Advantage
58
Guangzhou LES biological Technology Co.,Ltd.
Tel
;
Fax
-
Email
3307355104@qq.com;3307355104@qq.com
Country
China
ProdList
3652
Advantage
58
Capot Chemical Co.,Ltd.
Tel
+86-571-85586718
Fax
+86-571-85864795
Email
sales@capotchem.com
Country
China
ProdList
20012
Advantage
60
Aikon International Limited
Tel
025-58859352-
Fax
02557626880
Email
hywu@aikonchem.com
Country
China
ProdList
16029
Advantage
58
Wuhan FengyaoTonghui Chemical Products Co., Ltd.
Tel
027-87466205
Email
2678564200@qq.com
Country
China
ProdList
18991
Advantage
58
More
Less

View Lastest Price from AMPRENAVIR manufacturers

Zhuozhou Wenxi import and Export Co., Ltd
Product
Amprenavir 161814-49-9
Price
US $15.00-10.00/KG
Min. Order
1KG
Purity
99%+ HPLC
Supply Ability
Monthly supply of 1 ton
Release date
2021-07-10
Zhuozhou Wenxi import and Export Co., Ltd
Product
Amprenavir 161814-49-9
Price
US $15.00-10.00/KG
Min. Order
1KG
Purity
99%+ HPLC
Supply Ability
Monthly supply of 1 ton
Release date
2021-07-09
Dideu Industries Group Limited
Product
AMPRENAVIR USP/EP/BP 161814-49-9
Price
US $1.10/g
Min. Order
1g
Purity
99.9%
Supply Ability
100 Tons Min
Release date
2021-06-23

161814-49-9, AMPRENAVIRRelated Search:


  • KVX-478
  • AGENERASE
  • AMPRENAVIR
  • 141W94
  • PROZEI
  • 141W94, KVX-478, Agenerase, Prozei,
  • Carbamic acid, (1S,2R)-3-(4-aminophenyl)sulfonyl(2-methylpropyl)amino-2-hydroxy-1-(phenylmethyl)propyl-, (3S)-tetrahydro-3-furanyl ester
  • Angenerase
  • Carbamic acid, [3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-, tetrahydro-3-furanyl ester, [3S-[3R*(1R*,2S*)]]-
  • VX 478
  • AMPRENAVIR (VX-478)
  • CS-1052
  • (3S)-oxolan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-1-phenylbutan-2-yl]carbamate
  • [(3S)-Oxolan-3-yl] N-[(2S,3R)-4-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
  • N-[(1S,2R)-3-[[(4-AMinophenyl)sulfonyl](2-Methylpropyl)aMino]-2-hydroxy-1-(phenylMethyl)propyl]carbaMic Acid (3S)-Tetrahydro-3-furanyl Ester
  • AMprenavir(agenerase)
  • Amprenavir(KVX-478)
  • Carbamic acid, N-[(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-, (3S)-tetrahydro-3-furanyl ester
  • AMPRENAVIR USP/EP/BP
  • 161814-49-9
  • C25H35N3O6S
  • Inhibitor
  • peptides
  • API
  • Anti-viral Compounds
  • Anti-virals
  • Inhibitors
  • Intermediates & Fine Chemicals
  • Non-nucleoside Reverse Transcriptase
  • Pharmaceuticals