DELAVIRDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H28N6O3S
Molecular Weight	456.561
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

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

InChI

InChIKey=WHBIGIKBNXZKFE-UHFFFAOYSA-N

InChI=1S/C22H28N6O3S/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/h4-8,13-15,24-26H,9-12H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C22H28N6O3S
Molecular Weight	456.561
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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. .

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 reverse transcriptase	Inhibitor		21.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection	Primary		Approved	RESCRIPTOR

C_max

Value	Dose	Analyte	Population
12.6 μM	200 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
18.8 μM	300 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
26.6 μM	400 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
2.18 μM	200 mg 3 times / day steady-state, oral	N-DESISOPROPYL DELAVIRDINE plasma	Homo sapiens
2.88 μM	300 mg 3 times / day steady-state, oral	N-DESISOPROPYL DELAVIRDINE plasma	Homo sapiens
3.23 μM	400 mg 3 times / day steady-state, oral	N-DESISOPROPYL DELAVIRDINE plasma	Homo sapiens
35 μM	400 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
180 μM × h	400 mg 3 times / day steady-state, oral		DELAVIRDINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
2.59 h	200 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
3.33 h	300 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
4.12 h	400 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
4.71 h	200 mg 3 times / day steady-state, oral	N-DESISOPROPYL DELAVIRDINE plasma	Homo sapiens
6.18 h	300 mg 3 times / day steady-state, oral	N-DESISOPROPYL DELAVIRDINE plasma	Homo sapiens
7.5 h	400 mg 3 times / day steady-state, oral	N-DESISOPROPYL DELAVIRDINE plasma	Homo sapiens
5.8 h	400 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens

F_unbound

Value	Dose	Analyte	Population
2.3%	200 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
2.3%	300 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
2.3%	400 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens
2%	400 mg 3 times / day steady-state, oral	DELAVIRDINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
400 mg 3 times / day steady, oral Highest studied dose	unhealthy, >18 years	Disc. AE: Rash, Oral lesion... Other AEs: Fever, Thrombocytopenia...
400 mg 3 times / day multiple, oral Highest studied dose	unhealthy	Disc. AE: Rash...

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AEs

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AE	Significance	Dose	Population
Fatigue	1 patient	400 mg 3 times / day steady, oral Highest studied dose	unhealthy, >18 years
Nausea	1 patient	400 mg 3 times / day steady, oral Highest studied dose	unhealthy, >18 years
Thrombocytopenia	1 patient	400 mg 3 times / day steady, oral Highest studied dose	unhealthy, >18 years
Oral lesion	1 patient Disc. AE	400 mg 3 times / day steady, oral Highest studied dose	unhealthy, >18 years
Function liver abnormal	2 patients Disc. AE	400 mg 3 times / day steady, oral Highest studied dose	unhealthy, >18 years

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor	substrate inhibitor

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A CYP2C19 P-gp MRP1 MRP2 MRP3 CYP1A2	CYP3A P-gp	P-gp

Drug as perpetrator

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Target	Modality	Activity
CYP1A2	inhibitor	negligible
MRP1	inhibitor	yes [Inhibition 16.7 uM]
MRP2	inhibitor	yes [Inhibition 16.7 uM]
MRP3	inhibitor	yes [Inhibition 16.7 uM]
CYP2D6	inhibitor	yes [Ki 12.8 uM]

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Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP2D6	substrate	likely
P-gp	substrate	no
CYP3A	substrate	yes	yes (co-administration study)

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:119573	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:119573
ChemicalBook	CB8292151	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8292151
eMolecules	1989427	https://www.emolecules.com/cgi-bin/more?vid=1989427
MolPort	MolPort-003-846-188	https://www.molport.com/shop/molecule-link/MolPort-003-846-188
ZINC	ZINC000018516586	http://zinc15.docking.org/substances/ZINC000018516586

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PubMed

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Title	Date	PubMed
Novel 2,2-dioxide-4,4-disubstituted-1,3-H-2,1,3-benzothiadiazines as non-nucleoside reverse transcriptase inhibitors.	2000 Jan 17	10673109
Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260).	2000 Mar	10681363
Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives.	2000 Mar 9	10715167
Inhibition of clinically relevant mutant variants of HIV-1 by quinazolinone non-nucleoside reverse transcriptase inhibitors.	2000 May 18	10821714
Clinical pharmacokinetics of non-nucleoside reverse transcriptase inhibitors.	2001	11735608

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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 Use Guide

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
Record UNII	DOL5F9JD3E
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DELAVIRDINE

Official Name

English

DELAVIRDINE [VANDF]

Common Name

English

Delavirdine [WHO-DD]

Common Name

English

PIPERAZINE, 1-(3-((1-METHYLETHYL)AMINO)-2-PYRIDINYL)-4-((5-((METHYLSULFONYL)AMINO)-1H-INDOL-2-YL)CARBONYL)-

Systematic Name

English

delavirdine [INN]

Common Name

English

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Classification Tree

Code System

Code

Reverse Transcriptase Inhibitors

NDF-RT

N0000009948

Non-nucleoside reverse transcriptase inhibitors

WHO-VATC

QJ05AG02

Antiviral: HIV

LIVERTOX

NBK547899

Analogs/Derivatives

NDF-RT

N0000175460

Reverse Transcriptase Inhibitor

NCI_THESAURUS

C97453

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Code System

Code

Type

Description

SMS_ID

100000083479

PRIMARY

CHEBI

119573

PRIMARY

DRUG BANK

DB00705

PRIMARY

NCI_THESAURUS

C65366

PRIMARY

LACTMED

Delavirdine

PRIMARY

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Related Record

Type

Details


					A3Z87NSO0U

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 POLYMERASE

TARGET ORGANISM->INHIBITOR

Comments:

Delavirdine has demonstrated an IC50 of 0.26 micromolar against recombinant reverse transcriptase; at 3 micromolar, it halted the spread of virus in MT-4 cells and blocked replication of primary HIV-1 isolates in peripheral blood lymphocytes, including zidovudine-resistant variants.


					L9DP834D1P

CYTOCHROME P450 2C9

METABOLIC ENZYME -> INDUCER


					421105KRQE

DELAVIRDINE MESYLATE

SALT/SOLVATE -> PARENT

Amount:


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MAJOR


					76UB6O122H

ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2

TRANSPORTER -> INHIBITOR

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Related Record

Type

Details


					TV9X4GSK6W

N-DESISOPROPYL DELAVIRDINE

METABOLITE -> PARENT

Comments:

Delavirdine is primarily metabolized by cytochrome P450 3A (CYP3A), but in vitro data suggest that delavirdine may also be metabolized by CYP2D6

Interaction Type:

MAJOR

Amount:

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Related Record

Type

Details


					DOL5F9JD3E

DELAVIRDINE

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Parameters
Biological Half-life	PHARMACOKINETIC	5.8 hours [2 to 11] (average)	3 TIMES DAILY DOSE 400 mg (average)

Tmax	PHARMACOKINETIC	1 hours (average)	ORAL ADMINISTRATION

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator