Compounds > mdl 100240
Page last updated: 2024-12-08

mdl 100240

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

Description

MDL 100240: a prodrug of MDL 100173; MDL 100142 is the (R)-isomer; MDL 100240 is the (S)-isomer; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID133985
SCHEMBL ID4135357
MeSH IDM0227337

Synonyms (22)

Synonym
142695-08-7
pyrido(2,1-a)(2)benzazepine-4-carboxylic acid, 7-((2-(acetylthio)-1-oxo-3-phenylpropyl)amino)-1,2,3,4,6,7,8,12b-octahydro-6-oxo-, (4s-(4alph,7alpha(r*),12bbeta))-
0k57643y3a ,
unii-0k57643y3a
mdl 100,142
mdl 100,240
m-100240
mdl-100240
mdl 100240
(4s,7s,12br)-7-[[(2s)-2-acetylsulfanyl-3-phenylpropanoyl]amino]-6-oxo-2,3,4,7,8,12b-hexahydro-1h-pyrido[2,1-a][2]benzazepine-4-carboxylic acid
SCHEMBL4135357
m 100240 [who-dd]
pyrido(2,1-a)(2)benzazepine-4-carboxylic acid, 7-((2-(acetylthio)-1-oxo-3-phenylpropyl)amino)-1,2,3,4,6,7,8,12b-octahydro-6-oxo-, (4s-(4.alpha.,7.alpha.(r*),12b.beta.))-
hoechst-marion roussel 100240
m 100240
pyrido(2,1-a)(2)benzazepine-4-carboxylic acid, 7-(((2s)-2-(acetylthio)-1-oxo-3-phenylpropyl)amino)-1,2,3,4,6,7,8,12b-octahydro-6-oxo-, (4s,7s,12br)-
m100240 ,
DTXSID00931603
7-{[2-(acetylsulfanyl)-1-hydroxy-3-phenylpropylidene]amino}-6-oxo-1,2,3,4,6,7,8,12b-octahydropyrido[2,1-a][2]benzazepine-4-carboxylic acid
(4s,7s,12br)-7-((s)-2-(acetylthio)-3-phenylpropanamido)-6-oxo-1,2,3,4,6,7,8,12b-octahydrobenzo[c]pyrido[1,2-a]azepine-4-carboxylic acid
Q27236888
AKOS040748895

Research Excerpts

Overview

MDL 100240 is a pro-drug that, upon conversion to MDL 100173, acts as a potent dual inhibitor of ACE and NEP.

ExcerptReferenceRelevance
"MDL 100240 is a pro-drug that, upon conversion to MDL 100173, acts as a potent dual inhibitor of ACE and NEP with a balanced activity on both enzymes."( Dual ACE and NEP inhibitors: a review of the pharmacological properties of MDL 100240.
Rossi, GP, 2003)		1.27

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic data were obtained from 12 young (ages 18-45 years, 10 male, 2 female) and 12 elderly (ages 65-85 years, 7 male, 5 female) healthy subjects in a parallel-group, open-label study."( Pharmacokinetics of M100240 and MDL 100,173, a dual angiotensin-converting enzyme/neutral endopeptidase inhibitor, in healthy young and elderly volunteers.
Argenti, R; Emmons, GT; Jensen, BK; Martin, LL; Martin, NE, 2004)		0.32
" Serial plasma concentrations of M100240 and MDL 100,173 were analyzed, and pharmacokinetic parameters were calculated with noncompartmental methods."( The effect of food on the pharmacokinetics of a dual angiotensin-converting enzyme/neutral endopeptidase inhibitor, M100240.
Barrett, JS; Brennan, B; Cirillo, I; Martin, NE, 2004)		0.32

Bioavailability

ExcerptReferenceRelevance
" The oral bioavailability of MDL 100,240 was estimated at 85%, not statistically different from 100%."( Bioavailability of repeated oral administration of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase in healthy volunteers.
Biollaz, J; Brunner, HR; Brunner-Ferber, F; Buclin, T; Nussberger, J; Rousso, P, 2000)		0.31
" In addition, the absolute bioavailability of an immediate-release formulation of M100240 was assessed."( Pharmacoscintigraphic assessment of the regional drug absorption of the dual angiotensin-converting enzyme/neutral endopeptidase inhibitor, M100240, in healthy volunteers.
Barrett, JS; Collison, KR; Martin, LL; Martin, NE; Tardif, S; Wilding, I; Wray, H, 2003)		0.32
"We predicted M100240 is likely to be well absorbed via passive diffusion across the human gastrointestinal tract following oral administration."( Permeation prediction of M100240 using the parallel artificial membrane permeability assay.
Hwang, KK; Jiang, L; Martin, NE; Zhu, C, )		0.13

Dosage Studied

ExcerptRelevanceReference
" Thus, severe hypertension and related CVD were regressed by MDL-100,240, which resulted to be as effective as a full dosage of ramipril in TGRen2."( Comparative effects of the dual ACE-NEP inhibitor MDL-100,240 and ramipril on hypertension and cardiovascular disease in endogenous angiotensin II-dependent hypertension.
Agabiti-Rosei, E; Bova, S; Neri, G; Nussdorfer, GG; Pessina, AC; Rizzoni, D; Rossi, GP; Sacchetto, A, 2002)		0.31
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (18)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's7 (38.89)18.2507
2000's11 (61.11)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: 10.97

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 Index10.97 (24.57)
Research Supply Index3.43 (2.92)
Research Growth Index4.40 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.97)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials9 (42.86%)5.53%
Reviews1 (4.76%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other11 (52.38%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
midazolam
Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.. midazolam : An imidazobenzodiazepine that is 4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted by a methyl, 2-fluorophenyl and chloro groups at positions 1, 6 and 8, respectively.		3.411imidazobenzodiazepine;
monofluorobenzenes;
organochlorine compound		anticonvulsant;
antineoplastic agent;
anxiolytic drug;
apoptosis inducer;
central nervous system depressant;
GABAA receptor agonist;
general anaesthetic;
muscle relaxant;
sedative
aldosterone
[no description available]		2.011011beta-hydroxy steroid;
18-oxo steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(4) steroid;
C21-steroid hormone;
mineralocorticoid;
primary alpha-hydroxy ketone;
steroid aldehyde		human metabolite;
mouse metabolite
mdl 100173
MDL 100173: (S)-isomer is MDL 100173; (R)-isomer is MDL 101628; RN refers to (4S-(4alpha,7alpha(R*),12bbeta)-isomer; structure given in first source		4.8642
angiotensin ii
Giapreza: injectable form of angiotensin II used to increase blood pressure in adult patients with septic or other distributive shock. Ile(5)-angiotensin II : An angiotensin II that acts on the central nervous system (PDB entry: 1N9V).		10.0452amino acid zwitterion;
angiotensin II		human metabolite
bradykinin
[no description available]		2.9140oligopeptidehuman blood serum metabolite;
vasodilator agent
ramipril
Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat.. ramipril : A dipeptide that is the prodrug for ramiprilat, the active metabolite obtained by hydrolysis of the ethyl ester group. An angiotensin-converting enzyme (ACE) inhibitor, used to treat high blood pressure and congestive heart failure.. quark : Quarks comprise one of two classes of the fundamental particles. Quarks possess fractional electric charges and are not observed in free state. The word "quark" first appears in James Joyce's Finnegans Wake and has been chosen by Murray Gell-Mann as a name for fundamental building blocks of particles.		2.9340azabicycloalkane;
cyclopentapyrrole;
dicarboxylic acid monoester;
dipeptide;
ethyl ester		bradykinin receptor B2 agonist;
cardioprotective agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor;
matrix metalloproteinase inhibitor;
prodrug
enalaprilat anhydrous
Enalaprilat: The active metabolite of ENALAPRIL and one of the potent, intravenously administered, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.. enalaprilat dihydrate : The dihydrate form of enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor that is used (often in the form of its prodrug, enalapril) in the treatment of hypertension and heart failure, for reduction of proteinuria and renal disease in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients. Unlike enalapril, enalaprilat is not absorbed by mouth but is administered by intravenous injection.. enalaprilat (anhydrous) : Enalapril in which the ethyl ester group has been hydrolysed to the corresponding carboxylic acid. Enalaprilat is an angiotensin-converting enzyme (ACE) inhibitor and is used (often in the form of its prodrug, enalapril) in the treatment of hypertension and heart failure, for reduction of proteinuria and renal disease in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients. Unlike enalapril, enalaprilat is not absorbed by mouth but is given by intravenous injection, usually as the dihydrate.		1.9910dicarboxylic acid;
dipeptide		antihypertensive agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor
icatibant
icatibant: a potent bradykinin (B2) receptor antagonist; WIN 65365 is an L-Tic(7) stereoisomer. icatibant : A ten-membered synthetic oligopeptide consisting of D-Arg, Arg, Pro, Hyp, Gly, Thi, Ser, D-Tic, Oic, and Arg residues joined in sequrence. A bradykinin receptor antagonist used as its acetate salt for the treatment of acute attacks of hereditary angioedema in adult patients.		2.4120
atrial natriuretic factor
Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.		4.341polypeptide
endothelin-1
Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)		1.9910
angiotensin i
Angiotensin I: A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.. angiotensin I : A ten amino acid peptide formed by renin cleavage of angiotensinogen. Angiotensin I has no direct biological function except that high levels can stimulate catecholamine production. It is metabolized to its biologically active byproduct angiotensin II, a potent vasoconstrictor, by angiotensin converting enzyme (ACE) through cleavage of the two terminal amino acids.. angiotensin I dizwitterion : A peptide zwitterion that is the dizwitterionic form of angiotensin I having both carboxy groups deprotonated and the aspartyl amino group and arginine side-chain protonated. It is the major species at pH 7.3.		8.7821angiotensin;
peptide zwitterion		human metabolite;
neurotransmitter agent
adrenomedullin
Adrenomedullin: A 52-amino acid peptide with multi-functions. It was originally isolated from PHEOCHROMOCYTOMA and ADRENAL MEDULLA but is widely distributed throughout the body including lung and kidney tissues. Besides controlling fluid-electrolyte homeostasis, adrenomedullin is a potent vasodilator and can inhibit pituitary ACTH secretion.		2.0110
cyclic gmp
Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed). 3',5'-cyclic GMP : A 3',5'-cyclic purine nucleotide in which the purine nucleobase is specified as guanidine.		3.38113',5'-cyclic purine nucleotide;
guanyl ribonucleotide		Escherichia coli metabolite;
human metabolite;
mouse metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
ConditionIndicatedRelationship StrengthStudiesTrials
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		02.4120
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.4220
Blood Pressure, High
[description not available]		05.8181
Hypertension
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.		05.8181
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.		03.3320
Cirrhosis
[description not available]		02.0310
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.		02.0310
Cardiac Failure
[description not available]		0210
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.		0210