Compounds > dmp 450
Page last updated: 2024-09-26

dmp 450

Description

DMP 450: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID154044
CHEMBL ID223824
SCHEMBL ID3455127
MeSH IDM0262000

Synonyms (27)

Synonym
bdbm151
chembl223824 ,
174391-92-5
mozenavir (inn)
D05538
mozenavir (*bismesylate salt*)
dmp450
xm412
dmp-450
(4r,5s,6s,7r)-1,3-bis[(3-aminophenyl)methyl]-4,7-dibenzyl-5,6-dihydroxy-1,3-diazepan-2-one
dmp 450
[4r-(4.alpha.,5.alpha.,6.beta.,7.beta.)]-1,3- bis[(3-aminophenyl)methyl]-hexahydro-5,6-dihydroxy-4,7-bis(phenylmethyl)-2h-1,3-diazepin-2-one dimethanesulfonate
[4-r-(-4-alpha,5-alpha,6-beta,7-beta)]-hexahydro-5,6-bis(hydroxy)-1,3-bis([(3-amino)phenyl]methyl)-4,7-bis(phenylmethyl)-2h-1,3-diazepinone
dmp450(inhibitor of dupont merck)
DB02102
mozenavir
1DMP
mozenavir [inn]
64oo8946er ,
(4r,5s,6s,7r)-1,3-bis(3-aminobenzyl)-4,7-dibenzylhexahydro-5,6-dihydroxy-2h-1,3-diazepin-2-one
unii-64oo8946er
SCHEMBL3455127
DTXSID40169822
(4r,5s,6s,7r)-1,3-bis(3-aminobenzyl)-4,7-dibenzyl-5,6-dihydroxy-1,3-diazepan-2-one
Q63390512
KYRSNWPSSXSNEP-ZRTHHSRSSA-N
2h-1,3-diazepin-2-one, 1,3-bis[(3-aminophenyl)methyl]hexahydro-5,6-dihydroxy-4,7-bis(phenylmethyl)-, (4r,5s,6s,7r)-

Research Excerpts

Overview

ExcerptReference
"DMP 450 is a significant advance within the cyclic urea class of HIV protease inhibitors due to its exceptional oral bioavailability. "( Aldrich, PE; Bacheler, LT; Chang, CH; Erickson-Viitanen, S; Eyermann, CJ; Garber, S; Grubb, M; Hodge, CN; Jackson, DA; Jadhav, PK; Korant, B; Lam, PY; Maurin, MB; Meek, JL; Otto, MJ; Rayner, MM; Reid, C; Sharpe, TR; Shum, L; Winslow, DL, 1996)

Protein Targets (6)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, HIV-1 PROTEASEHuman immunodeficiency virus 1Ki0.00030.00030.00030.0003AID977610
Chain B, HIV-1 PROTEASEHuman immunodeficiency virus 1Ki0.00030.00030.00030.0003AID977610
Gag-Pol polyproteinHuman immunodeficiency virus type 1 (BRU ISOLATE)Ki0.00030.00000.08283.3000AID1795214
Gag-Pol polyproteinHIV-1 M:B_HXB2RKi0.00030.00000.51449.0000AID1795292
Protease Human immunodeficiency virus 1Ki0.00030.00000.04433.1000AID160292; AID160316; AID160454; AID160458; AID160474; AID162710; AID163483; AID82912
[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)
Thromboxane-A synthaseRattus norvegicus (Norway rat)IC90 (µMol)0.12500.01040.07030.1250AID210277
Protease Human immunodeficiency virus 1IC90 (µMol)0.12250.00200.67847.3000AID105206; AID210277
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (2)

Processvia Protein(s)Taxonomy
viral life cycleGag-Pol polyproteinHIV-1 M:B_HXB2R
establishment of integrated proviral latencyGag-Pol polyproteinHIV-1 M:B_HXB2R
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (2)

Processvia Protein(s)Taxonomy
peptidase activityGag-Pol polyproteinHIV-1 M:B_HXB2R
integrase activityGag-Pol polyproteinHIV-1 M:B_HXB2R
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (41)

Assay IDTitleYearJournalArticle
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.
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.
AID14284Bioavailability as maximal plasma concentration in rats after 10 mg/kg oral dose1998Journal of medicinal chemistry, Jun-04, Volume: 41, Issue:12
Cyclic HIV protease inhibitors: design and synthesis of orally bioavailable, pyrazole P2/P2' cyclic ureas with improved potency.
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.
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.
AID104232The antiviral potency (IC90) was assessed by measuring their effect on the accumulation of viral RNA transcripts on HIV-1 RF infected MT-2 cells1998Journal of medicinal chemistry, Apr-23, Volume: 41, Issue:9
Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: synthesis, structure-activity relationships, and X-ray crystal structure studies.
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.
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.
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.
AID163483Binding affinity for HIV-1 protease enzyme was measured by using fluorescent peptide substrate1998Journal of medicinal chemistry, Apr-23, Volume: 41, Issue:9
Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: synthesis, structure-activity relationships, and X-ray crystal structure studies.
AID82610Antiviral activity against mutant virus HIV-1 mutant (84V) strain1998Journal 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.
AID82609Antiviral activity against indinavir virus (HIV-1 mutated at 10R/63P/71V/82F/84V and resistant to indinavir)1998Journal 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.
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.
AID25130Half life (10 mg/kg, intravenously) determined by administering intravenously in dogs1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
AID19831Partition coefficient (logP) (HPLC)1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
AID18200Oral bioavailability in dog (dose 10 mg/kg)1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
AID104224Antiviral activity by measuring its effect on the accumulation of viral RNA transcripts on infection of MT-2 cells with HIV-1 RF.1999Journal of medicinal chemistry, Jan-14, Volume: 42, Issue:1
Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors.
AID82611Antiviral activity against mutant virus HIV-1 mutant (84V/82F) strain1998Journal 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.
AID160458Inhibition of HIV protease, measured by assaying the cleavage of a fluorescent peptide substrate using HPLC1998Journal of medicinal chemistry, Jun-04, Volume: 41, Issue:12
Cyclic HIV protease inhibitors: design and synthesis of orally bioavailable, pyrazole P2/P2' cyclic ureas with improved potency.
AID210277Inhibition of HIV RNA synthesis in T-cell line1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
AID22996Apparent volume of distribution of compound (10 mg/kg, intravenously) in dogs1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
AID82612Antiviral activity against ritonavir virus (HIV-1 mutated at 46I/63P/71V/82F/84V and resistant to ritonavir)1998Journal 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.
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.
AID15511Clearance (10 mg/kg, intravenously) in dog plasma1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
AID227243Whole cell antiviral activity.1998Bioorganic & medicinal chemistry letters, Apr-07, Volume: 8, Issue:7
The synthesis and evaluation of cyclic ureas as HIV protease inhibitors: modifications of the P1/P1' residues.
AID14055Maximum concentration (10 mg/kg, orally) in plasma of dogs1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
AID25131Half life (10 mg/kg, orally) determined by administering intravenously in dog plasma1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
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.
AID14635The maximum plasma concentration (Cmax) is the observed peak plasma concentration after an oral dose on rat.1999Journal of medicinal chemistry, Jan-14, Volume: 42, Issue:1
Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors.
AID82912HIV protease inhibition.1998Bioorganic & medicinal chemistry letters, Apr-07, Volume: 8, Issue:7
The synthesis and evaluation of cyclic ureas as HIV protease inhibitors: modifications of the P1/P1' residues.
AID162710Affinity against HIV protease1997Journal of medicinal chemistry, Dec-05, Volume: 40, Issue:25
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
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.
AID104229Concentration which reduced the concentration of HIV viral RNA by 90% from the level measured in an untreated infected culture1998Journal of medicinal chemistry, Jun-04, Volume: 41, Issue:12
Cyclic HIV protease inhibitors: design and synthesis of orally bioavailable, pyrazole P2/P2' cyclic ureas with improved potency.
AID282343Inhibition of HIV1 protease2004Journal of medicinal chemistry, Dec-30, Volume: 47, Issue:27
A combined QM/MM approach to protein--ligand interactions: polarization effects of the HIV-1 protease on selected high affinity inhibitors.
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.
AID160454Inhibition constant of HIV protease inhibitors1999Journal of medicinal chemistry, Jan-14, Volume: 42, Issue:1
Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors.
AID977610Experimentally measured binding affinity data (Ki) for protein-ligand complexes derived from PDB1996Chemistry & biology, Apr, Volume: 3, Issue:4
Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450.
AID1811Experimentally measured binding affinity data derived from PDB1996Chemistry & biology, Apr, Volume: 3, Issue:4
Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450.
AID1799449Protease Inhibtion Assay from Article 10.1016/s1074-5521(98)90117-x: \\Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors.\\1998Chemistry & biology, Oct, Volume: 5, Issue:10
Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors.
AID1795292Protease Inhibition Assay from Article 10.1021/jm9803626: \\Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors.\\1999Journal of medicinal chemistry, Jan-14, Volume: 42, Issue:1
Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors.
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 (23)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's18 (78.26)18.2507
2000's4 (17.39)29.6817
2010's1 (4.35)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (4.35%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other22 (95.65%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceDescriptionRelationhip StrengthStudiesTrialsClassesRoles
dmp 323[no description available]medium150diazepanone;
ureas		anti-HIV agent;
metabolite
xv 638[no description available]medium401,3-thiazoles;
benzamides;
diazepanone;
diol;
secondary alcohol;
secondary carboxamide;
ureas		HIV protease inhibitor
xk 263[no description available]medium40
amprenavir[no description available]medium40carbamate ester;
sulfonamide;
tetrahydrofuryl ester		antiviral drug;
HIV protease inhibitor
ritonavir[no description available]medium501,3-thiazoles;
carbamate ester;
carboxamide;
L-valine derivative;
ureas		antiviral drug;
environmental contaminant;
HIV protease inhibitor;
xenobiotic
saquinavir[no description available]medium30L-asparagine derivative;
quinolines		antiviral drug;
HIV protease inhibitor
indinavir sulfate[no description available]medium40dicarboxylic acid diamide;
N-(2-hydroxyethyl)piperazine;
piperazinecarboxamide		HIV protease inhibitor
nelfinavir[no description available]medium30aryl sulfide;
benzamides;
organic heterobicyclic compound;
phenols;
secondary alcohol;
tertiary amino compound		antineoplastic agent;
HIV protease inhibitor
dmp 850[no description available]medium20
tipranavir[no description available]medium10sulfonamideantiviral drug;
HIV protease inhibitor
urea[no description available]medium140isourea;
monocarboxylic acid amide;
one-carbon compound		Daphnia magna metabolite;
Escherichia coli metabolite;
fertilizer;
flour treatment agent;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
hexacarbonyltungsten[no description available]medium10
tungsten[no description available]medium10chromium group element atommicronutrient
acetonitrile[no description available]medium10aliphatic nitrile;
volatile organic compound		EC 3.5.1.4 (amidase) inhibitor;
NMR chemical shift reference compound;
polar aprotic solvent
potassium phosphate[no description available]medium10inorganic phosphate salt;
inorganic potassium salt
methanol[no description available]medium10alkyl alcohol;
one-carbon compound;
primary alcohol;
volatile organic compound		amphiprotic solvent;
Escherichia coli metabolite;
fuel;
human metabolite;
mouse metabolite;
Mycoplasma genitalium metabolite
efavirenz[no description available]medium10acetylenic compound;
benzoxazine;
cyclopropanes;
organochlorine compound;
organofluorine compound		antiviral drug;
HIV-1 reverse transcriptase inhibitor
indazoles[no description available]medium10indazole
lactose[no description available]medium10lactose
dimethylacetamide[no description available]medium10acetamides;
monocarboxylic acid amide		human metabolite
carbamates[no description available]medium10amino-acid anion
ConditionIndicatedRelationship StrengthStudiesTrials
HIV0low30
HIV Coinfection0low10
HIV Infections0low10
HTLV-III Infections0low10
HTLV-III-LAV Infections0low10
Sensitivity and Specificity0low20
T-Lymphotropic Virus Type III Infections, Human0low10

Research Highlights

Safety/Toxicity (1)

ArticleYear
Inhibitor docking screened by the modified SAFE_p scoring function: application to cyclic urea HIV-1 PR inhibitors.
Journal of computational chemistry, Volume: 28, Issue: 13		2007
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Pharmacokinetics (1)

ArticleYear
Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450.
Chemistry & biology, Volume: 3, Issue: 4		1996
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioavailability (7)

ArticleYear
Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors.
Journal of medicinal chemistry, Jan-14, Volume: 42, Issue: 1		1999
Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors.
Chemistry & biology, Volume: 5, Issue: 10		1998
Nonsymmetric P2/P2' cyclic urea HIV protease inhibitors. Structure-activity relationship, bioavailability, and resistance profile of monoindazole-substituted P2 analogues.
Journal of medicinal chemistry, Jun-18, Volume: 41, Issue: 13		1998
Cyclic HIV protease inhibitors: design and synthesis of orally bioavailable, pyrazole P2/P2' cyclic ureas with improved potency.
Journal of medicinal chemistry, Jun-04, Volume: 41, Issue: 12		1998
Nonsymmetrically substituted cyclic urea HIV protease inhibitors.
Journal of medicinal chemistry, Dec-05, Volume: 40, Issue: 25		1997
Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450.
Chemistry & biology, Volume: 3, Issue: 4		1996
Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.
Journal of medicinal chemistry, Aug-30, Volume: 39, Issue: 18		1996
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]