Compounds > xv 638
Page last updated: 2024-11-08

xv 638

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

XV638 : A member of the class of diazepanones that is 1,3-diazepane which is substituted by a 3-(1,3-thiazol-2-ylcarbamoyl)benzyl group at positions 1 and 3, oxo group at position 2, hydroxy groups at positions 5S and 6S, and benzyl groups at positions 4R and 7R. It is a potent HIV-1 protease inhibitor. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID441046
CHEMBL ID57375
CHEBI ID10050
MeSH IDM0290653

Synonyms (27)

Synonym
chembl57375 ,
3-{[(4r,5s,6s,7r)-4,7-dibenzyl-5,6-dihydroxy-2-oxo-3-{[3-(1,3-thiazol-2-ylcarbamoyl)phenyl]methyl}-1,3-diazepan-1-yl]methyl}-n-(1,3-thiazol-2-yl)benzamide
bdbm154
[4r-(4alpha,5alpha,6beta,7beta)]-3,3'-[[tetrahydro-5,6-dihydroxy-2-oxo-4,7-bis(phenylmethyl)-1h-1,3-diazepine-1,3(2h)-diyl] bis(methylene)]bis[n-2-thiazolylbenzamide]
[4r-(4alpha,5alpha,6beta,7beta)]-3,3'-[[tetrahydro-5,6-dihydroxy-2-oxo-4,7-bis(phenylmethyl)-1h-1,3-diazepine-1,3(2h)-d iyl] bis(methylene)]bis[n-2-thiazolylbenzamide]
xv6 ,
C06488
xv638
[4r-(4alpha,5alpha,6beta,7beta)]-3,3'-[[tetrahydro-5,6-dihydroxy-2-oxo-4,7-bis(phenylmethyl)-1h-1,3-diazepine-1,3(2h)-diyl]bis(methylene)]bis[n-2-thiazolylbenzamide]
183854-11-7
3-[[(4r,5s,6s,7r)-4,7-dibenzyl-5,6-dihydroxy-2-oxo-3-[[3-(thiazol-2-ylcarbamoyl)phenyl]methyl]-1,3-diazepan-1-yl]methyl]-n-thiazol-2-yl-benzamide
1BWA ,
1BV9
DB02702
1BV7
1QBR
3-[[(4r,5s,6s,7r)-4,7-dibenzyl-5,6-dihydroxy-2-oxo-3-[[3-(1,3-thiazol-2-ylcarbamoyl)phenyl]methyl]-1,3-diazepan-1-yl]methyl]-n-(1,3-thiazol-2-yl)benzamide
(4r-(4alpha,5alpha,6beta,7beta))-3,3'-((tetrahydro-5,6-dihydroxy-2-oxo-4,7-bis(phenylmethyl)-1h-1,3-diazepine-1,3(2h)-diyl)-bis(methylene))bis(n-2-thiazolylbenzamide)
3,3'-{[(4r,5s,6s,7r)-4,7-dibenzyl-5,6-dihydroxy-2-oxo-1,3-diazepane-1,3-diyl]bis(methylene)}bis[n-(1,3-thiazol-2-yl)benzamide]
CHEBI:10050
xv-638
DTXSID90171490
[4r-(4alpha,5alpha,6beta,7beta)]-3,3'-[[tetrahydro-5,6-dihydroxy-2-oxo-4,7-bis(phenylmethyl)-1h-1,3-diazepine-1,3(2h)-d
3,3'-{[(4r,5s,6s,7r)-4,7-dibenzyl-5,6-dihydroxy-2-oxo-1,3-diazepane-1,3-diyl]dimethanediyl}bis(n-1,3-thiazol-2-ylbenzamide)
iyl] bis(methylene)]bis[n-2-thiazolylbenzamide]
Q27467642
AKOS040754477

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
" The small size probably contributes to the observed good oral bioavailability in animals."( Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.
Aldrich, PE; Bacheler, LT; Chang, CH; Confalone, PN; Daneker, WF; DeLucca, GV; Emmett, G; Eyermann, CJ; Han, Q; Hodge, CN; Holler, ER; Jadhav, PK; Klabe, RM; Kornhauser, DM; Lam, PY; Li, L; Li, R; Markwalder, JA; McHugh, RJ; Rayner, MM; Ru, Y; Seitz, SP; Sharpe, TR; Shum, L; Winslow, DL, 1996)		0.29
" Using this approach several very potent (IC90 11 nM) and orally bioavailable (F% 93-100%) compounds were discovered (21, 22)."( Nonsymmetric P2/P2' cyclic urea HIV protease inhibitors. Structure-activity relationship, bioavailability, and resistance profile of monoindazole-substituted P2 analogues.
Bacheler, LT; Cordova, B; De Lucca, GV; Erickson-Viitanen, S; Garber, S; Kim, UT; Klabe, RM; Ko, SS; Lam, GN; Liang, J; Logue, KA; Trainor, GL; Wright, MR, 1998)		0.3
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
HIV protease inhibitorAn inhibitor of HIV protease, an enzyme required for production of proteins needed for viral assembly.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (7)

ClassDescription
1,3-thiazoles
benzamides
ureas
diazepanone
secondary carboxamideA carboxamide resulting from the formal condensation of a carboxylic acid with a primary amine; formula RC(=O)NHR(1).
diolA compound that contains two hydroxy groups, generally assumed to be, but not necessarily, alcoholic. Aliphatic diols are also called glycols.
secondary alcoholA secondary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has two other carbon atoms attached to it.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (16)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, PROTEIN (HIV-1 PROTEASE)Human immunodeficiency virus 1Ki0.00100.00010.00100.0025AID977610
Chain B, PROTEIN (HIV-1 PROTEASE)Human immunodeficiency virus 1Ki0.00100.00010.00100.0025AID977610
Chain A, PROTEIN (HIV-1 PROTEASE)Human immunodeficiency virus 1Ki0.00100.00010.00100.0025AID977610
Chain B, PROTEIN (HIV-1 PROTEASE)Human immunodeficiency virus 1Ki0.00100.00010.00100.0025AID977610
Chain A, PROTEIN (HIV-1 PROTEASE)Human immunodeficiency virus 1Ki0.00100.00010.00100.0025AID977610
Chain B, PROTEIN (HIV-1 PROTEASE)Human immunodeficiency virus 1Ki0.00100.00010.00100.0025AID977610
Chain A, PROTEIN (HIV-1 PROTEASE)Human immunodeficiency virus 1Ki0.00100.00010.00100.0025AID977610
Chain B, PROTEIN (HIV-1 PROTEASE)Human immunodeficiency virus 1Ki0.00100.00010.00100.0025AID977610
Chain A, HIV-1 PROTEASEHuman immunodeficiency virus 1Ki0.00000.00000.00000.0000AID977610
Chain B, HIV-1 PROTEASEHuman immunodeficiency virus 1Ki0.00000.00000.00000.0000AID977610
Chain A, HIV-1 PROTEASEHuman immunodeficiency virus 1Ki0.00000.00000.00000.0000AID977610
Chain B, HIV-1 PROTEASEHuman immunodeficiency virus 1Ki0.00000.00000.00000.0000AID977610
Chain A, HIV-1 PROTEASEHuman immunodeficiency virus 1Ki0.00000.00000.00000.0000AID977610
Chain B, HIV-1 PROTEASEHuman immunodeficiency virus 1Ki0.00000.00000.00000.0000AID977610
Gag-Pol polyproteinHuman immunodeficiency virus type 1 (BRU ISOLATE)Ki0.00000.00000.08283.3000AID1795214
Protease Human immunodeficiency virus 1Ki0.00000.00000.04433.1000AID160292; AID160316; AID160474; AID163487
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Protease Human immunodeficiency virus 1IC90 (µMol)0.00420.00200.67847.3000AID105206
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (20)

Assay IDTitleYearJournalArticle
AID16449Calculated partition coefficient (clogP)1996Journal of medicinal chemistry, Oct-11, Volume: 39, Issue:21
HIV protease inhibitory bis-benzamide cyclic ureas: a quantitative structure-activity relationship analysis.
AID160474Inhibitory activity against HIV protease1998Journal of medicinal chemistry, Jun-18, Volume: 41, Issue:13
Nonsymmetric P2/P2' cyclic urea HIV protease inhibitors. Structure-activity relationship, bioavailability, and resistance profile of monoindazole-substituted P2 analogues.
AID163487Inhibitory activity against HIV-1 protease1996Journal of medicinal chemistry, Oct-11, Volume: 39, Issue:21
HIV protease inhibitory bis-benzamide cyclic ureas: a quantitative structure-activity relationship analysis.
AID235096Resistance of constructed mutant 82F virus was calculated as (IC90 for a mutant virus / IC90 of wt HXB2 virus). 1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID210298The concentration required to inhibit HIV-1 RNA synthesis by 90%. Viral RNA quantified by a sandwich hybridization assay1996Journal of medicinal chemistry, Oct-11, Volume: 39, Issue:21
HIV protease inhibitory bis-benzamide cyclic ureas: a quantitative structure-activity relationship analysis.
AID160292Inhibition of HIV-1 protease1999Journal of medicinal chemistry, Jan-28, Volume: 42, Issue:2
Three-dimensional quantitative structure-activity relationship study on cyclic urea derivatives as HIV-1 protease inhibitors: application of comparative molecular field analysis.
AID235098Resistance of constructed mutant ABT538 virus was calculated as (IC90 for a mutant virus / IC90 of wt HXB2 virus)1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID235093Resistance of constructed mutant 461/47V/50V virus was calculated as (IC90 for a mutant virus / IC90 of wt HXB2 virus). 1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID235094Resistance of constructed mutant 48V/90M virus was calculated as (IC90 for a mutant virus / IC90 of wt HXB2 virus)1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID105206Inhibitory concentration against accumulation of viral p24 antigen following infection of MT-4 cells1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID104226Antiviral potency evaluated by measuring accumulation of viral RNA transcripts 3 days after infection of MT-2 cells with HIV-1 RF1998Journal of medicinal chemistry, Jun-18, Volume: 41, Issue:13
Nonsymmetric P2/P2' cyclic urea HIV protease inhibitors. Structure-activity relationship, bioavailability, and resistance profile of monoindazole-substituted P2 analogues.
AID235099Resistance of constructed mutant MK639 virus was calculated as (IC90 for a mutant virus / IC90 of wt HXB2 virus). 1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID235097Resistance of constructed mutant 84V virus was calculated as (IC90 for a mutant virus / IC90 of wt HXB2 virus). 1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID235095Resistance of constructed mutant 82A virus was calculated as (IC90 for a mutant virus / IC90 of wt HXB2 virus). 1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID160316Binding affinity to inhibit the purified wild-type HIV-1 Protease1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID1811Experimentally measured binding affinity data derived from PDB1998Biochemistry, Oct-27, Volume: 37, Issue:43
Counteracting HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with XV638 and SD146, cyclic urea amides with broad specificities.
AID977610Experimentally measured binding affinity data (Ki) for protein-ligand complexes derived from PDB1998Biochemistry, Oct-27, Volume: 37, Issue:43
Counteracting HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with XV638 and SD146, cyclic urea amides with broad specificities.
AID977610Experimentally measured binding affinity data (Ki) for protein-ligand complexes derived from PDB1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID1811Experimentally measured binding affinity data derived from PDB1997Journal of medicinal chemistry, Jan-17, Volume: 40, Issue:2
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
AID1795214Protease Inhibition Assay from Article 10.1021/jm9602571: \\Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.\\1996Journal of medicinal chemistry, Aug-30, Volume: 39, Issue:18
Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (6)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's6 (100.00)18.2507
2000's0 (0.00)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 12.50

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index12.50 (24.57)
Research Supply Index1.95 (2.92)
Research Growth Index4.45 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (12.50)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other6 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
amprenavir
[no description available]		2.3920carbamate ester;
sulfonamide;
tetrahydrofuryl ester		antiviral drug;
HIV protease inhibitor
dmp 323
(4R,5S,6S,7R)-4,7-dibenzyl-5,6-dihydroxy-1,3-bis[4-(hydroxymethyl)benzyl]-1,3-diazepan-2-one : A 1,3-diazepanone ring with two 4-(hydroxymethyl)benzyl groups as substituents at positions N-1 and N-4, two benzyl groups at C-4 and C-7, and two hydroxy groups at C-5 and C-6 respectively.		3.0950diazepanone;
ureas		anti-HIV agent;
metabolite
dmp 450
DMP 450: structure in first source		2.9140
ritonavir
Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.. ritonavir : An L-valine derivative that is L-valinamide in which alpha-amino group has been acylated by a [(2-isopropyl-1,3-thiazol-4-yl)methyl]methylcarbamoyl group and in which a hydrogen of the carboxamide amino group has been replaced by a (2R,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl group. A CYP3A inhibitor and antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS, it is often used as a fixed-dose combination with another protease inhibitor, lopinavir. Also used in combination with dasabuvir sodium hydrate, ombitasvir and paritaprevir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.		2.39201,3-thiazoles;
carbamate ester;
carboxamide;
L-valine derivative;
ureas		antiviral drug;
environmental contaminant;
HIV protease inhibitor;
xenobiotic
saquinavir
Saquinavir: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.. saquinavir : An aspartic acid derivative obtained by formal condensation of the primary amino group of (2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl]-3-hydroxy-1-phenylbutan-2-ylamine with the carboxy group of N(2)(-quinolin-2-ylcarbonyl)-L-asparagine. An inhibitor of HIV-1 protease.		2.3920L-asparagine derivative;
quinolines		antiviral drug;
HIV protease inhibitor
xk 263
[no description available]		2.6930
indinavir sulfate
Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.		2.3920dicarboxylic acid diamide;
N-(2-hydroxyethyl)piperazine;
piperazinecarboxamide		HIV protease inhibitor
ConditionIndicatedRelationship StrengthStudiesTrials
Sensitivity and Specificity
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)		01.9910