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Details

Stereochemistry ACHIRAL
Molecular Formula C22H28N6O3S.CH4O3S
Molecular Weight 552.667
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DELAVIRDINE MESYLATE

SMILES

CS(O)(=O)=O.CC(C)NC1=C(N=CC=C1)N2CCN(CC2)C(=O)C3=CC4=C(N3)C=CC(NS(C)(=O)=O)=C4

InChI

InChIKey=MEPNHSOMXMALDZ-UHFFFAOYSA-N
InChI=1S/C22H28N6O3S.CH4O3S/c1-15(2)24-19-5-4-8-23-21(19)27-9-11-28(12-10-27)22(29)20-14-16-13-17(26-32(3,30)31)6-7-18(16)25-20;1-5(2,3)4/h4-8,13-15,24-26H,9-12H2,1-3H3;1H3,(H,2,3,4)

HIDE SMILES / InChI

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C22H28N6O3S
Molecular Weight 456.561
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Delavirdine is a nonnucleoside reverse transcriptase inhibitor (NNRTI). Delavirdine binds directly to reverse transcriptase (RT) and blocks RNA-dependent and DNA-dependent DNA polymerase activities. Delavirdine does not compete with template:primer or deoxynucleoside triphosphates. HIV-2 RT and human cellular DNA polymerases alfa, gamma, or delta are not inhibited by delavirdine. In addition, HIV-1 group O, a group of highly divergent strains that are uncommon in North America, may not be inhibited by delavirdine. Delavirdine is marketed under the trade name Rescriptor, indicated for the treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted. .

Originator

Curator's Comment: # Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RESCRIPTOR

Approved Use

RESCRIPTOR Tablets are indicated for the treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted. The following should be considered before initiating therapy with RESCRIPTOR in treatment-naive patients. There are insufficient data directly comparing antiretroviral regimens containing RESCRIPTOR with currently preferred 3-drug regimens for initial treatment of HIV. In studies comparing regimens consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) (currently considered suboptimal) to RESCRIPTOR plus 2 NRTIs, the proportion of patients receiving the regimen containing RESCRIPTOR who achieved and sustained an HIV-1 RNA level <400 copies/mL over 1 year of therapy was relatively low (see DESCRIPTION OF CLINICAL STUDIES). Resistant virus emerges rapidly when RESCRIPTOR is administered as monotherapy. Therefore, RESCRIPTOR should always be administered in combination with other antiretroviral agents.

Launch Date

8.6011203E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.18 μM
200 mg 3 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
N-DESISOPROPYL DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.88 μM
300 mg 3 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
N-DESISOPROPYL DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.23 μM
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
N-DESISOPROPYL DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
35 μM
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
12.6 μM
200 mg 3 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
18.8 μM
300 mg 3 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
26.6 μM
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
180 μM × h
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.71 h
200 mg 3 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
N-DESISOPROPYL DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6.18 h
300 mg 3 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
N-DESISOPROPYL DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7.5 h
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
N-DESISOPROPYL DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
5.8 h
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.59 h
200 mg 3 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.33 h
300 mg 3 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4.12 h
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.3%
200 mg 3 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.3%
300 mg 3 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.3%
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAVIRDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Disc. AE: Rash, Oral lesion...
Other AEs: Fever, Thrombocytopenia...
AEs leading to
discontinuation/dose reduction:
Rash (grade 3-4, 36%)
Oral lesion (1 patient)
Function liver abnormal (2 patients)
Headache (grade 4, 1 patient)
Other AEs:
Fever (grade 3, 1 patient)
Thrombocytopenia (1 patient)
Nausea (1 patient)
Fatigue (1 patient)
Sources:
400 mg 3 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: multiple
Dose: 400 mg, 3 times / day
Sources:
unhealthy
n = 412
Health Status: unhealthy
Population Size: 412
Sources:
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (3.2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Fatigue 1 patient
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Nausea 1 patient
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Thrombocytopenia 1 patient
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Oral lesion 1 patient
Disc. AE
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Function liver abnormal 2 patients
Disc. AE
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Fever grade 3, 1 patient
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Rash grade 3-4, 36%
Disc. AE
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Headache grade 4, 1 patient
Disc. AE
400 mg 3 times / day steady, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, >18 years
n = 30
Health Status: unhealthy
Condition: HIV infection
Age Group: >18 years
Sex: M+F
Population Size: 30
Sources:
Rash 3.2%
Disc. AE
400 mg 3 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 3 times / day
Route: oral
Route: multiple
Dose: 400 mg, 3 times / day
Sources:
unhealthy
n = 412
Health Status: unhealthy
Population Size: 412
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
negligible
yes [Inhibition 16.7 uM]
yes [Inhibition 16.7 uM]
yes [Inhibition 16.7 uM]
yes [Ki 12.8 uM]
yes [Ki 2.6 uM]
yes [Ki 24 uM]
yes [Ki 9.5 uM]
yes (co-administration study)
Comment: coadministration of amprenavir with delavirdine resulted in an approximately 4-fold increase in amprenavir AUC to infinity (AUC∞) and a 6-fold increase in amprenavir Cmin
Page: 3.0
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
no
yes
yes (co-administration study)
Comment: Coadministration of RESCRIPTOR and drugs that induce CYP3A, such as rifampin, may decrease delavirdine plasma concentrations and reduce its therapeutic effect. With rifampin: 97% decrease in AUC
Page: 3.0
PubMed

PubMed

TitleDatePubMed
Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1.
1999 Dec
Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues.
1999 Oct 7
Structure-based design of non-nucleoside reverse transcriptase inhibitors of drug-resistant human immunodeficiency virus.
1999 Sep
Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors.
2000 Apr 10
Mutational analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors.
2000 May
A single amino acid change at Leu-188 in the reverse transcriptase of HIV-2 and SIV renders them sensitive to non-nucleoside reverse transcriptase inhibitors.
2001
Delavirdine: clinical pharmacokinetics and drug interactions.
2001
Identification of a putative binding site for [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)thymine (TSAO) derivatives at the p51-p66 interface of HIV-1 reverse transcriptase.
2001 Jun 7
A randomized trial of nelfinavir, ritonavir, or delavirdine in combination with saquinavir-SGC and stavudine in treatment-experienced HIV-1-infected patients.
2001 Mar-Apr
Combination therapy with indinavir, ritonavir, and delavirdine and nucleoside reverse transcriptase inhibitors in patients with HIV/AIDS who have failed multiple antiretroviral combinations.
2001 May-Jun
Drugs for HIV infection.
2001 Nov 26
HIV-protease inhibitors alter retinoic acid synthesis.
2001 Oct 19
Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection.
2002
Lack of hepatotoxicity associated with nonnucleoside reverse transcriptase inhibitors.
2002 Apr 1
Determination of delavirdine in very small volumes of plasma by high-performance liquid chromatography with fluorescence detection.
2002 Apr 5
Effect of delavirdine on plasma lipids and lipoproteins in patients receiving antiretroviral therapy.
2002 Sep 6
Pharmacokinetic interaction between amprenavir and delavirdine after multiple-dose administration in healthy volunteers.
2003 Jan
Modest decreases in NNRTI susceptibility do not influence virological outcome in patients receiving initial NNRTI-containing triple therapy.
2003 Oct
Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants.
2004 May 6
Patents

Sample Use Guides

In Vivo Use Guide
HIV-1 infection (part of combination): Oral: 400 mg 3 times/day
Route of Administration: Oral
In vitro anti-HIV-1 activity of delavirdine was assessed by infecting cell lines of lymphoblastic and monocytic origin and peripheral blood lymphocytes with laboratory and clinical isolates of HIV-1. IC50 and IC90 values (50% and 90% inhibitory concentrations) for laboratory isolates (n = 5) ranged from 0.005 to 0.030 uM and 0.04 to 0.10 uM, respectively. Mean IC50 of clinical isolates (n = 74) was 0.038 uM (range: 0.001 to 40 0.69 uM); 73 of 74 clinical isolates had an IC50
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:01:05 UTC 2023
Edited
by admin
on Wed Jul 05 23:01:05 UTC 2023
Record UNII
421105KRQE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DELAVIRDINE MESYLATE
HSDB   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
DELAVIRDINE MESILATE [JAN]
Common Name English
DELAVIRDINE METHANESULFONATE [MI]
Common Name English
DELAVIRDINE MESILATE
JAN   MART.  
Common Name English
DELAVIRDINE MESYLATE [ORANGE BOOK]
Common Name English
DELAVIRDINE METHANESULFONATE
MI  
Common Name English
U-90152S
Code English
DELAVIRDINE MESYLATE [VANDF]
Common Name English
RESCRIPTOR
Brand Name English
Delavirdine mesylate [WHO-DD]
Common Name English
PIPERAZINE, 1-(3-((1-METHYLETHYL)AMINO)-2-PYRIDINYL)-4-((5-((METHYLSULPHONYL)AMINO)-1H-INDOL-2-YL)CARBONYL)-, MONOMETHANESULPHONATE
Systematic Name English
DELAVIRDINE MESYLATE [USAN]
Common Name English
PIPERAZINE, 1-(3-((1-METHYLETHYL)AMINO)-2-PYRIDINYL)-4-((5-((METHYLSULFONYL)AMINO)-1H-INDOL-2-YL)CARBONYL)-, MONOMETHANESULFONATE
Systematic Name English
DELAVIRDINE MESYLATE [HSDB]
Common Name English
DELAVIRDINE MESILATE [MART.]
Common Name English
1-(3-(ISOPROPYLAMINO)-2-PYRIDYL)-4-((5-METHANESULPHONAMIDOINDOL-2-YL)CARBONYL)PIPERAZINE MONOMETHANESULPHONATE
Systematic Name English
1-[3-(Isopropylamino)-2-pyridyl]-4-[(5-methanesulfonamidoindol-2-yl)carbonyl]piperazine monomethanesulfonate
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C97453
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
Code System Code Type Description
SMS_ID
100000088391
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
HSDB
7162
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
CHEBI
4379
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
EVMPD
SUB01575MIG
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
PUBCHEM
441386
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
DRUG BANK
DBSALT000038
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
FDA UNII
421105KRQE
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
CAS
147221-93-0
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
EPA CompTox
DTXSID701017136
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
MERCK INDEX
M4152
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY Merck Index
NCI_THESAURUS
C28974
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
RXCUI
142152
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY RxNorm
ChEMBL
CHEMBL593
Created by admin on Wed Jul 05 23:01:05 UTC 2023 , Edited by admin on Wed Jul 05 23:01:05 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
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ACTIVE MOIETY