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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H37N3O7S.C2H6O
Molecular Weight 593.732
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DARUNAVIR ETHANOLATE

SMILES

CCO.CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CO[C@H]3OCC[C@@H]23)S(=O)(=O)C4=CC=C(N)C=C4

InChI

InChIKey=QWSHKNICRJHQCY-VBTXLZOXSA-N
InChI=1S/C27H37N3O7S.C2H6O/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26;1-2-3/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32);3H,2H2,1H3/t22-,23-,24+,25-,26+;/m0./s1

HIDE SMILES / InChI

Molecular Formula C2H6O
Molecular Weight 46.0684
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C27H37N3O7S
Molecular Weight 547.664
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23708741 | http://adisinsight.springer.com/drugs/800016726

Darunavir (trade name Prezista) is an orally active bis-furan-sulfonamide inhibitor of human immunodeficiency virus (HIV-1) protease. Darunavir was developed by Tibotec Pharmaceuticals (now Janssen R&D Ireland). Darunavir is indicated for the treatment of HIV-1 infection in adult and pediatric patients 3 years of age and older. The drug is co-administered with low-dose ritonavir and other anti-HIV agents. It is the only antiretroviral that has been registered at two different doses, 800/100 mg once-daily or 600/100 mg twice-daily, allowing its administration throughout the entire course of HIV disease, from naive subjects without any HIV-1 resistance to heavily treatment-experienced subjects with widespread triple-class family resistance.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.5 pM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PREZISTA

Approved Use

PREZISTA is a human immunodeficiency virus (HIV-1) protease inhibitor indicated for the treatment of HIV-1 infection in adult patients. PREZISTA is also indicated for the treatment of HIV-1 infection in pediatric patients 3 years of age and older. PREZISTA must be co-administered with ritonavir (PREZISTA/ritonavir) and with other antiretroviral agents.

Launch Date

2006
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5272 ng/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
57055 ng × h/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
93026 ng × h/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
124698 ng × h/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
126377 ng × h/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15 h
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
15 h
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5%
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy, 43
Health Status: unhealthy
Age Group: 43
Sex: M+F
Sources:
Disc. AE: Headache, Gastrointestinal disorder NOS...
AEs leading to
discontinuation/dose reduction:
Headache (grade 3, 0.79%)
Gastrointestinal disorder NOS (5.51%)
Sources:
3200 mg single, oral
Overdose
Dose: 3200 mg
Route: oral
Route: single
Dose: 3200 mg
Sources:
healthy
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Drug-induced hepatitis, Hepatitis acute...
AEs leading to
discontinuation/dose reduction:
Drug-induced hepatitis
Hepatitis acute
Cytolytic hepatitis
Reaction skin (grade 1-3)
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Diabetes mellitus
Hyperglycemia
Fat redistribution
Fat tissue increased
Immune reconstitution syndrome
Sources:
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (grade 1-2, 0.5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal disorder NOS 5.51%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy, 43
Health Status: unhealthy
Age Group: 43
Sex: M+F
Sources:
Headache grade 3, 0.79%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy, 43
Health Status: unhealthy
Age Group: 43
Sex: M+F
Sources:
Cytolytic hepatitis Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Diabetes mellitus Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Drug-induced hepatitis Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Fat redistribution Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Fat tissue increased Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Hepatitis acute Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Hyperglycemia Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Immune reconstitution syndrome Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Stevens-Johnson syndrome Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Toxic epidermal necrolysis Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Reaction skin grade 1-3
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Rash grade 1-2, 0.5%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
PubMed

PubMed

TitleDatePubMed
Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro.
2003 Oct
[New drugs--hope for salvage patients?].
2005 Apr 25
[Protease inhibitors].
2005 Dec
Stereoselective and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol.
2005 Dec 22
A lame duck, a dark horse, and a goat.
2005 May-Jun
Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs.
2005 Oct
Report from the 13th retrovirus conference. New data on TMC114 and TMC125.
2006 Apr
Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385.
2006 Apr 1
Anti-HIV agents. Darunavir shows its strength.
2006 Aug-Sep
Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M.
2006 Feb 23
FDA approves new PI.
2006 Jun
Drug interactions. Interactions with TMC114 and TMC125.
2006 Jun-Jul
New HIV treatment.
2006 Sep-Oct
Clinical pharmacokinetics of darunavir.
2007
Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers.
2007
Pharmacokinetic interaction between TMC114/r and efavirenz in healthy volunteers.
2007
Fast and simultaneous determination of darunavir and eleven other antiretroviral drugs for therapeutic drug monitoring: method development and validation for the determination of all currently approved HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in human plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
2007
Pharmacokinetics of darunavir (TMC114) and atazanavir during coadministration in HIV-negative, healthy volunteers.
2007
Antiretroviral treatment of HIV infection: Swedish recommendations 2007.
2007
AIDS in the Third World: how to stop the HIV infection?
2007
Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir.
2007 Apr 1
Darunavir (TMC114): a new HIV-1 protease inhibitor.
2007 Aug
Darunavir: a second-generation protease inhibitor.
2007 Aug 1
Overview of boosted protease inhibitors in treatment-experienced HIV-infected patients.
2007 Dec
Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV.
2007 Dec 15
Darunavir (TMC114) approved by the FDA.
2007 Feb
Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1.
2007 Feb 19
A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism.
2007 Jan
Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance.
2007 Jul 11
Safety, tolerability, and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced, hepatitis B or C co-infected patients in POWER 1 and 3.
2007 Jul-Aug
A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro.
2007 Jun
Prediction of clinical benefits of ritonavir-boosted TMC114 from treatment effects on CD4 counts and HIV RNA.
2007 May
Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors.
2007 Oct
Quantification of darunavir (TMC114) in human plasma by high-performance liquid chromatography with ultra-violet detection.
2007 Oct 1
Predicting HIV care costs using CD4 counts from clinical trials.
2007 Sep
Lessons Learned From 2 Patients With Multidrug-Resistant HIV-1 Infection Successfully Treated With a Darunavir-Containing Antiretroviral Treatment Regimen.
2007 Sep
Tipranavir: a new option for the treatment of drug-resistant HIV infection.
2007 Sep 15
Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease.
2007 Sep 6
Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance.
2008 Jan
Quality control of protease inhibitors.
2008 Jun
Patents

Sample Use Guides

Treatment-naïve adult patients and treatment-experienced adult patients with no darunavir resistance associated substitutions: 800 mg (two 400 mg tablets) taken with ritonavir 100 mg once daily and with food. Treatment-experienced adult patients with at least one darunavir resistance associated substitution: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food. Pediatric patients (3 to less than 18 years of age and weighing at least 10 kg): dosage of PREZISTA and ritonavir is based on body weight and should not exceed the treatmentexperienced adult dose. Do not use once daily dosing in pediatric patients. PREZISTA should be taken with ritonavir twice daily and with food.
Route of Administration: Oral
Darunavir exhibits activity against laboratory strains and clinical isolates of HIV-1 and laboratory strains of HIV-2 in acutely infected T-cell lines, human peripheral blood mononuclear cells and human monocytes/macrophages with median EC50 values ranging from 1.2 to 8.5 nM (0.7 to 5.0 ng/mL). Darunavir demonstrates antiviral activity in cell culture against a broad panel of HIV-1 group M (A, B, C, D, E, F, G), and group O primary isolates with EC50 values ranging from less than 0.1 to 4.3 nM.
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:08:25 GMT 2025
Edited
by admin
on Mon Mar 31 18:08:25 GMT 2025
Record UNII
33O78XF0BW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DARUNAVIR ETHANOLATE
JAN   MART.   ORANGE BOOK   VANDF   WHO-DD  
Common Name English
DARUNAVIR MONOETHANOLATE
MI  
Preferred Name English
PREZISTA
Brand Name English
(3R,3AS,6AR)-HEXAHYDROFURO(2,3-B)FURAN-3-YL ((1S,2R)-3-(((4-AMINOPHENYL)SULFONYL)(ISOBUTYL)AMINO)-1-BENZYL-2-HYDROXYPROPYL)CARBAMATE - ETHANOL (1:1)
Common Name English
DARUNAVIR MONOETHANOLATE [MI]
Common Name English
Darunavir Ethanolate [WHO-DD]
Common Name English
REZOLSTA
Brand Name English
CARBAMIC ACID, ((1S,2R)-3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-, (3R,3AS,6AR)-HEXAHYDROFURO(2,3-B)FURAN-3-YL ESTER, COMPD. WITH ETHANOL (1:1)
Common Name English
DARUNAVIR ETHANOLATE [JAN]
Common Name English
DARUNAVIR (AS ETHANOLATE)
Common Name English
TMC114 ETHANOLATE
Common Name English
((1S,2R)-3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)- CARBAMIC ACID (3R,3AS,6AR)-HEXAHYDROFURO(2,3-B)FURAN-3-YL ESTER MONOETHANOLATE
Common Name English
DARUNAVIR ETHANOLATE [ORANGE BOOK]
Common Name English
DARUNAVIR ETHANOLATE [VANDF]
Common Name English
SYMTUZA COMPONENT DARUNAVIR
Common Name English
PREZCOBIX COMPONENT DARUNAVIR ETHANOLATE
Brand Name English
DARUNAVIR ETHANOLATE [MART.]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS REZOLSTA (AUTHORIZED: HIV INFECTIONS)
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
NCI_THESAURUS C783
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
EMA ASSESSMENT REPORTS PREZISTA (AUTHORIZED: HIV INFECTIONS)
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
Code System Code Type Description
PUBCHEM
23725083
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
MERCK INDEX
m4099
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY Merck Index
RXCUI
644682
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY RxNorm
FDA UNII
33O78XF0BW
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
DAILYMED
33O78XF0BW
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
DRUG BANK
DBSALT001338
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
EVMPD
SUB23573
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
SMS_ID
100000091852
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
ChEMBL
CHEMBL1323
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
CAS
635728-49-3
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
NCI_THESAURUS
C77389
Created by admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
PRIMARY
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ANHYDROUS->SOLVATE
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