Compounds > ditekiren
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ditekiren

Description

ditekiren: orally active renin inhibitor [MeSH]

Cross-References

ID SourceID
PubMed CID5464201
CHEMBL ID303323
CHEMBL ID1790497
SCHEMBL ID122368
MeSH IDM0145103

Synonyms (35)

Synonym
l-histidinamide, 1-((1,1-dimethylethoxy)carbonyl)-l-prolyl-l-phenylalanyl-n-(2-hydroxy-5-methyl-1-(2-methylpropyl)-4-(((2-methyl-1-(((2-pyridinylmethyl)amino)carbonyl)butyl)amino)carbonyl)hexyl)-n(sup alpha)-methyl-, (1s-(1r*,2r*,4r*(1r*,2r*)))-
ditekirenum [inn-latin]
ditiquireno [inn-spanish]
tert-butyl (2s)-2-(((alphas)-alpha-(((1s)-1-(((1s,2s,4s)-2-hydroxy-1-isobutyl-5-methyl-4-(((1s,2s)-2-methyl-1-((2-pyridylmethyl)carbamoyl)butyl)carbamoyl)hexyl)carbamoyl)-2-imidazol-4-ylethyl)methylcarbamoyl)phenethyl)carbamoyl)-1-pyrrolidinecarboxylate
ditekiren [usan:inn]
ditekiren
l-histidinamide, 1-((1,1-dimethylethoxy)carbonyl)-l-prolyl-l-phenylalanyl-n-(2-hydroxy-5-methyl-1-(2-methylpropyl)-4-(((2-methyl-1-(((2-pyridinylemthyl)amino)carbonyl)butyl)amino)carbonyl)hexyl)-nalpha-methyl-, (1s-(1r*,2r*,4r*(1r*,2r*)))-
ditekirene [inn-french]
ditekiren (usan)
D03741
103336-05-6
u-71038
u 71038
tert-butyl (2s)-2-[[(2s)-1-[[(2s)-1-[[(4s,5s,7s)-5-hydroxy-2,8-dimethyl-7-[[(2s,3s)-3-methyl-1-oxo-1-(pyridin-2-ylmethylamino)pentan-2-yl]carbamoyl]nonan-4-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]p
bdbm50024156
chembl303323
2-(1-{[1-(2-hydroxy-1-isobutyl-5-methyl-4-{2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-hexylcarbamoyl)-2-(3h-imidazol-4-yl)-ethyl]-methyl-carbamoyl}-2-phenyl-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
mcmc-6317
CHEMBL1790497 ,
unii-5355s3w1is
ditekirenum
ditekirene
5355s3w1is ,
ditiquireno
bdbm50368278
l-histidinamide, 1-((1,1-dimethylethoxy)carbonyl)-l-prolyl-l-phenylalanyl-n-(2-hydroxy-5-methyl-1-(2-methylpropyl)-4-(((2-methyl-1-(((2-pyridinylmethyl)amino)carbonyl)butyl)amino)carbonyl)hexyl)-n(sup .alpha.)-methyl-, (1s-(1r*,2r*,4r*(1r*,2r*)))-
ditekiren [usan]
ditekiren [inn]
tert-butyl (2s)-2-[[(alphas)-alpha-[[(1s)-1-[[(1s,2s,4s)-2-hydroxy-1-isobutyl-5-methyl-4-[[(1s,2s)-2-methyl-1-[(2-pyridylmethyl)carbamoyl]butyl]carbamoyl]hexyl]carbamoyl]-2-imidazol-4-ylethyl]methylcarbamoyl]phenethyl]carbamoyl]-1-pyrrolidinecarboxylate
SCHEMBL122368
DTXSID40145787
Q27261065
tert-butyl (s)-2-(((4s,7s,9s,10s,13s,16s)-13-((1h-imidazol-4-yl)methyl)-4-((s)-sec-butyl)-9-hydroxy-10-isobutyl-7-isopropyl-14-methyl-3,6,12,15-tetraoxo-17-phenyl-1-(pyridin-2-yl)-2,5,11,14-tetraazaheptadecan-16-yl)carbamoyl)pyrrolidine-1-carboxylate
AT38268
AKOS040746778

Protein Targets (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
Pepsin ASus scrofa (pig)IC506.8000AID156723
ReninHomo sapiens (human)IC500.0003AID198478
ReninHomo sapiens (human)Ki0.0000AID198986
Cathepsin D Bos taurus (cattle)IC506.3000AID47824

Other Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
Multidrug resistance protein 1aRattus norvegicus (Norway rat)Km19.1000AID681452

Bioassays (10)

Assay IDTitleYearJournalArticle
AID681668TP_TRANSPORTER: increase in Calcein-AM intracellular accumulation (Calcein-AM: 1 uM, Ditekiren: 20 uM) in Bsep-expressing LLC-PK1 cells2000Molecular pharmacology, Jan, Volume: 57, Issue:1
ISSN: 0026-895X		Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.
AID156723Inhibition of porcine pepsin1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
ISSN: 0022-2623		Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo.
AID198470Inhibition of human plasma renin1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
ISSN: 0022-2623		Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo.
AID198512In vitro inhibitory activity against human plasma renin1988Journal of medicinal chemistry, Jan, Volume: 31, Issue:1
ISSN: 0022-2623		Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu psi[CH(OH)CH2]Val or leu psi[CH2NH]Val substitutions.
AID47824Inhibition of bovine cathepsin D1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
ISSN: 0022-2623		Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo.
AID679778TP_TRANSPORTER: increase in Calcein-AM intracellular accumulation (Calcein-AM: 1 uM, Ditekiren: 20 uM) in MDR1-expressing LLC-PK1 cells2000Molecular pharmacology, Jan, Volume: 57, Issue:1
ISSN: 0026-895X		Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.
AID198478In vitro inhibition of human renin by radio-immuno assay of angiotensin I (ANG I)1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
ISSN: 0022-2623		Determination of dissociation constants of high affinity (pM) human renin inhibitors: application to analogues of ditekiren (U-71,038).
AID17660The dissociation constant determined by fluorescence displacement assay1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
ISSN: 0022-2623		Determination of dissociation constants of high affinity (pM) human renin inhibitors: application to analogues of ditekiren (U-71,038).
AID681452TP_TRANSPORTER: uptake, inhibited by Cyclosporine, Nicardipine, Daunomycin, Verapamil, Reserpine, Rhodamine 123 and Vinblastine in bile canalicular membrane vesicles1997The Journal of pharmacology and experimental therapeutics, Apr, Volume: 281, Issue:1
ISSN: 0022-3565		Characterization of the hepatic canalicular membrane transport of a model oligopeptide: ditekiren.
AID198986In vitro inhibition constants using recombinant human renin assay1991Journal of medicinal chemistry, Jul, Volume: 34, Issue:7
ISSN: 0022-2623		Determination of dissociation constants of high affinity (pM) human renin inhibitors: application to analogues of ditekiren (U-71,038).

Research

Studies (23)

TimeframeStudies, This Drug (%)All Drugs %
pre-19906 (26.09)18.7374
1990's16 (69.57)18.2507
2000's1 (4.35)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (3.85%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other25 (96.15%)84.16%
SubstanceStudiesClassesRolesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
reserpine
1
alkaloid ester;
methyl ester;
yohimban alkaloid		adrenergic uptake inhibitor;
antihypertensive agent;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
environmental contaminant;
first generation antipsychotic;
plant metabolite;
xenobiotic		2000200024.0low001000
vincristine
1
acetate ester;
formamides;
methyl ester;
organic heteropentacyclic compound;
organic heterotetracyclic compound;
tertiary alcohol;
tertiary amino compound;
vinca alkaloid		antineoplastic agent;
drug;
microtubule-destabilising agent;
plant metabolite;
tubulin modulator		2000200024.0low001000
taurocholic acid
1
amino sulfonic acid;
bile acid taurine conjugate		human metabolite2000200024.0low001000
vinblastine
1
2000200024.0low001000
daunorubicin
1
aminoglycoside antibiotic;
anthracycline;
p-quinones;
tetracenequinones		antineoplastic agent;
bacterial metabolite		2000200024.0low001000
paclitaxel
1
taxane diterpenoid;
tetracyclic diterpenoid		antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent		2000200024.0low001000
h 142
1
1988198836.0low010000
digoxin
1
cardenolide glycoside;
steroid saponin		anti-arrhythmia drug;
cardiotonic drug;
EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor;
epitope		2000200024.0low001000
tamoxifen
1
stilbenoid;
tertiary amino compound		angiogenesis inhibitor;
antineoplastic agent;
bone density conservation agent;
EC 1.2.3.1 (aldehyde oxidase) inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
estrogen antagonist;
estrogen receptor antagonist;
estrogen receptor modulator		2000200024.0low001000
cyclosporine
1
homodetic cyclic peptideanti-asthmatic drug;
anticoronaviral agent;
antifungal agent;
antirheumatic drug;
carcinogenic agent;
dermatologic drug;
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
geroprotector;
immunosuppressive agent;
metabolite		2000200024.0low001000
pepstatin
2
pentapeptide;
secondary carboxamide		bacterial metabolite;
EC 3.4.23.* (aspartic endopeptidase) inhibitor		1986198837.0low020000
rhodamine 123
1
organic chloride salt;
xanthene dye		fluorochrome2000200024.0low001000
SubstanceStudiesClassesRolesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
urea
1
isourea;
monocarboxylic acid amide;
one-carbon compound		Daphnia magna metabolite;
Escherichia coli metabolite;
fertilizer;
flour treatment agent;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite		1990199034.0low001000
phenobarbital
1
barbituratesanticonvulsant;
drug allergen;
excitatory amino acid antagonist;
sedative		1997199727.0low001000
tromethamine
1
primary amino compound;
triol		buffer1990199034.0low001000
captopril
3
alkanethiol;
L-proline derivative;
N-acylpyrrolidine;
pyrrolidinemonocarboxylic acid		antihypertensive agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor		1989199134.0medium012000
enalkiren
1
peptide1991199133.0low001000
angiotensin ii
1
amino acid zwitterion;
angiotensin II		human metabolite1991199133.0low001000
glucosamine
1
D-glucosamineEscherichia coli metabolite;
geroprotector;
mouse metabolite		1990199034.0low001000
ro 42-5892
1
cyclopropanes;
diol;
L-histidine derivative;
secondary carboxamide;
sulfone		antihypertensive agent;
EC 3.4.23.15 (renin) inhibitor;
peptidomimetic;
vasodilator agent		1991199133.0low001000
renin inhibitory peptide
2
1990199034.0medium002000
angiotensin i
2
angiotensin;
peptide zwitterion		human metabolite;
neurotransmitter agent		1990199332.5low002000
ConditionIndicatedStudiesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
Anesthesia0
1
1990199034.0medium001000
Blood Pressure, High0
2
1989199134.0high011000
Blood Pressure, Low0
1
1991199133.0medium001000
Extravascular Hemolysis0
1
1991199133.0medium001000
Hemolysis0
1
1991199133.0medium001000
Hypertension0
2
1989199134.0high011000
Hypotension0
1
1991199133.0medium001000

Pharmacokinetics (1)

ArticleYear
Development of a sensitive activity assay for high-volume evaluation of human renin inhibitory peptides in rat serum: results with U-71,038.
Pharmaceutical research, , Volume: 7, Issue:4		1990

Bioavailability (2)

ArticleYear
A primate bioassay for the determination of renin inhibitory peptides in serum.
Analytical biochemistry, , Volume: 186, Issue:1		1990
Renin inhibitors in hypertension.
Clinical nephrology, , Volume: 36, Issue:4		1991

Dosage (5)

ArticleYear
Hepatic elimination in the rat of ditekiren (U-71038), a renin inhibitor pseudohexapeptide.
Drug metabolism and disposition: the biological fate of chemicals, , Volume: 21, Issue:1
Disposition, metabolism, and excretion of U-71038, a novel renin inhibitor peptide, in the rat.
Drug metabolism and disposition: the biological fate of chemicals, , Volume: 17, Issue:5
Development of a sensitive activity assay for high-volume evaluation of human renin inhibitory peptides in rat serum: results with U-71,038.
Pharmaceutical research, , Volume: 7, Issue:4		1990
A primate bioassay for the determination of renin inhibitory peptides in serum.
Analytical biochemistry, , Volume: 186, Issue:1		1990
Renin inhibitors in hypertension.
Clinical nephrology, , Volume: 36, Issue:4		1991