Compounds > n,n'-((5-(2-amino-5-(2-methylpropyl)-4-thiazolyl)-2-furanyl)phosphinylidene)bis(alanine) diethyl ester
Page last updated: 2024-12-11

n,n'-((5-(2-amino-5-(2-methylpropyl)-4-thiazolyl)-2-furanyl)phosphinylidene)bis(alanine) diethyl ester

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Description

N,N'-((5-(2-amino-5-(2-methylpropyl)-4-thiazolyl)-2-furanyl)phosphinylidene)bis(alanine) diethyl ester: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9811837
CHEMBL ID259771
SCHEMBL ID2669405
MeSH IDM0487958

Synonyms (26)

Synonym
CHEMBL259771 ,
mb06322
bdbm50322043
(2s,2''s)-diethyl 2,2''-((5-(2-amino-5-isobutylthiazol-4-yl)furan-2-yl)phosphoryl)bis(azanediyl)dipropanoate
ethyl (2s)-2-[({5-[2-amino-5-(2-methylpropyl)-1,3-thiazol-4-yl]furan-2-yl}({[(2s)-1-ethoxy-1-oxopropan-2-yl]amino})phosphoryl)amino]propanoate
mb 06322
r132917 ,
r 132917
mb-6322
cs 917
gp-3034
gp 3034
cs917 cpd
mb-06322 ,
n,n'-((5-(2-amino-5-(2-methylpropyl)-4-thiazolyl)-2-furanyl)phosphinylidene)bis(alanine) diethyl ester
r-132917
gp3034
managlinat dialanetil [inn]
3w93f83k7s ,
unii-3w93f83k7s
diethyl n,n'-(5-(2-amino-5-(2-methylpropyl)-1,3-thiazol-4-yl)furan-2-ylphosphonoyl)di-l-alaninate
SCHEMBL2669405
DB05518
ethyl (2s)-2-[[[5-[2-amino-5-(2-methylpropyl)-1,3-thiazol-4-yl]furan-2-yl]-[[(2s)-1-ethoxy-1-oxopropan-2-yl]amino]phosphoryl]amino]propanoate
Q27258128
AKOS040742098

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
"The purpose of this analysis was to develop a population pharmacokinetic model for CS-917, an oral hypoglycemic prodrug, and its 3 metabolites."( Population pharmacokinetic model for a novel oral hypoglycemic formed in vivo: comparing the use of active metabolite data alone versus using data of upstream and downstream metabolites.
Carrothers, TJ; Habtemariam, B; Kastrissios, H; Khariton, T; Kshirsagar, S; Mager, DE; Rohatagi, S; Walker, JR, 2012)		0.38

Bioavailability

ExcerptReferenceRelevance
"Like most phosphonic acids, the recently discovered potent and selective thiazole phosphonic acid inhibitors of fructose 1,6-bisphosphatase (FBPase) exhibited low oral bioavailability (OBAV) and therefore required a prodrug to achieve oral efficacy."( Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors.
Cashion, DK; Dang, Q; Erion, MD; Fan, K; Fujitaki, JM; Jiang, T; Kasibhatla, SR; Liu, Y; Potter, SC; Reddy, KR; Schulz, W; Taplin, F; van Poelje, PD, 2008)		0.35
" Various phosphonate prodrugs were explored without success, until a novel phosphonic diamide prodrug approach was implemented, which delivered compound 30j with good oral bioavailability (OBAV) (22-47%)."( Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of fructose-1,6-bisphosphatase.
Cashion, DK; Dang, Q; DaRe, J; Erion, MD; Fan, Y; Gibson, T; Jacintho, JD; Jiang, T; Kasibhatla, SR; Lemus, R; Li, H; Li, W; Liu, Y; Potter, SC; Sun, Z; Taplin, F; Tian, F; van Poelje, PD, 2011)		0.37

Dosage Studied

ExcerptRelevanceReference
" In addition, we describe acute effect of CS-917 on fasting hyperglycemia in overnight-fasted GK rats and chronic effect of CS-917 in multiple dosing GK rats."( CS-917, a fructose 1,6-bisphosphatase inhibitor, improves postprandial hyperglycemia after meal loading in non-obese type 2 diabetic Goto-Kakizaki rats.
Fujiwara, T; Hagisawa, Y; Izumi, M; Ohsumi, J; Okuno, A; Takahashi, K; Yoshida, T, 2008)		0.35
" The population pharmacokinetic model was used to predict exposure of the active moiety R-125338 and thus to identify potential CS-917 dosage reduction criteria."( Population pharmacokinetic model for a novel oral hypoglycemic formed in vivo: comparing the use of active metabolite data alone versus using data of upstream and downstream metabolites.
Carrothers, TJ; Habtemariam, B; Kastrissios, H; Khariton, T; Kshirsagar, S; Mager, DE; Rohatagi, S; Walker, JR, 2012)		0.38
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Fructose-1,6-bisphosphatase 1Homo sapiens (human)IC50 (µMol)0.01000.01002.00979.8000AID492056
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (20)

Processvia Protein(s)Taxonomy
negative regulation of transcription by RNA polymerase IIFructose-1,6-bisphosphatase 1Homo sapiens (human)
fructose 6-phosphate metabolic processFructose-1,6-bisphosphatase 1Homo sapiens (human)
gluconeogenesisFructose-1,6-bisphosphatase 1Homo sapiens (human)
regulation of gluconeogenesisFructose-1,6-bisphosphatase 1Homo sapiens (human)
dephosphorylationFructose-1,6-bisphosphatase 1Homo sapiens (human)
negative regulation of cell growthFructose-1,6-bisphosphatase 1Homo sapiens (human)
response to nutrient levelsFructose-1,6-bisphosphatase 1Homo sapiens (human)
cellular response to insulin stimulusFructose-1,6-bisphosphatase 1Homo sapiens (human)
negative regulation of glycolytic processFructose-1,6-bisphosphatase 1Homo sapiens (human)
negative regulation of Ras protein signal transductionFructose-1,6-bisphosphatase 1Homo sapiens (human)
cellular response to magnesium ionFructose-1,6-bisphosphatase 1Homo sapiens (human)
cellular response to cAMPFructose-1,6-bisphosphatase 1Homo sapiens (human)
cellular response to xenobiotic stimulusFructose-1,6-bisphosphatase 1Homo sapiens (human)
cellular hyperosmotic salinity responseFructose-1,6-bisphosphatase 1Homo sapiens (human)
cellular hypotonic salinity responseFructose-1,6-bisphosphatase 1Homo sapiens (human)
cellular response to raffinoseFructose-1,6-bisphosphatase 1Homo sapiens (human)
cellular response to phorbol 13-acetate 12-myristateFructose-1,6-bisphosphatase 1Homo sapiens (human)
fructose 1,6-bisphosphate metabolic processFructose-1,6-bisphosphatase 1Homo sapiens (human)
fructose metabolic processFructose-1,6-bisphosphatase 1Homo sapiens (human)
sucrose biosynthetic processFructose-1,6-bisphosphatase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (7)

Processvia Protein(s)Taxonomy
protein bindingFructose-1,6-bisphosphatase 1Homo sapiens (human)
AMP bindingFructose-1,6-bisphosphatase 1Homo sapiens (human)
fructose 1,6-bisphosphate 1-phosphatase activityFructose-1,6-bisphosphatase 1Homo sapiens (human)
identical protein bindingFructose-1,6-bisphosphatase 1Homo sapiens (human)
metal ion bindingFructose-1,6-bisphosphatase 1Homo sapiens (human)
monosaccharide bindingFructose-1,6-bisphosphatase 1Homo sapiens (human)
RNA polymerase II-specific DNA-binding transcription factor bindingFructose-1,6-bisphosphatase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (4)

Processvia Protein(s)Taxonomy
nucleusFructose-1,6-bisphosphatase 1Homo sapiens (human)
cytoplasmFructose-1,6-bisphosphatase 1Homo sapiens (human)
cytosolFructose-1,6-bisphosphatase 1Homo sapiens (human)
extracellular exosomeFructose-1,6-bisphosphatase 1Homo sapiens (human)
cytoplasmFructose-1,6-bisphosphatase 1Homo sapiens (human)
cytosolFructose-1,6-bisphosphatase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (20)

Assay IDTitleYearJournalArticle
AID492058Antidiabetic activity in monkey hepatocytes assessed as inhibition of glucose production after 4 hrs2010Bioorganic & medicinal chemistry, Jul-15, Volume: 18, Issue:14
Discovery of potent and orally active tricyclic-based FBPase inhibitors.
AID344060Half life in cryopreserved human hepatocytes at 100 uM2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors.
AID492057Inhibition of monkey FBase2010Bioorganic & medicinal chemistry, Jul-15, Volume: 18, Issue:14
Discovery of potent and orally active tricyclic-based FBPase inhibitors.
AID344061Stability in human liver S9 fractions assessed as prodrug conversion per mg of protein2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors.
AID554219Antidiabetic activity in Sprague-Dawley rat assessed as decrease in glucose Cmax at 10 mg/kg, po2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of fructose-1,6-bisphosphatase.
AID554307Antihyperglycemic activity in Zucker fa/fa rat assessed as reduction in glucose level at 0.4 % w/w administered as food mixture2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of fructose-1,6-bisphosphatase.
AID598034Antidiabetic activity in db/db C57BLKS mouse assessed as reduction of plasma glucose level at 200 mg/kg, po administered 4 hrs after food removal measured after 6 hrs postdose relative to control2011Bioorganic & medicinal chemistry letters, Jun-01, Volume: 21, Issue:11
Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase.
AID554217Oral bioavailability in Sprague-Dawley rat at 10 mg/kg2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of fructose-1,6-bisphosphatase.
AID597862Antidiabetic activity in db/db C57BLKS mouse assessed as reduction of plasma glucose level at 200 mg/kg, po administered 4 hrs after food removal measured after 2 hrs postdose (Rbv = 22.73 +/- 0.73 mM)2011Bioorganic & medicinal chemistry letters, Jun-01, Volume: 21, Issue:11
Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase.
AID492056Inhibition of human FBase2010Bioorganic & medicinal chemistry, Jul-15, Volume: 18, Issue:14
Discovery of potent and orally active tricyclic-based FBPase inhibitors.
AID344056Reduction in blood glucose level in fasted Sprague-Dawley rat at 30 mg/kg, po relative to control2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors.
AID328937Oral bioavailability in rat2008Journal of medicinal chemistry, Apr-24, Volume: 51, Issue:8
Prodrugs of phosphates and phosphonates.
AID344055Bioavailability in fasted Sprague-Dawley rat assessed as urinary excretion of phosphoric acid at 10 to 50 mg/kg, po after 24 hrs by HPLC relative to iv dosed phosphoric acid2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors.
AID597863Antidiabetic activity in db/db C57BLKS mouse assessed as reduction of plasma glucose level at 200 mg/kg, po administered 4 hrs after food removal measured after 4 hrs postdose (Rbv = 26.58 +/- 1.09 mM)2011Bioorganic & medicinal chemistry letters, Jun-01, Volume: 21, Issue:11
Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase.
AID328938Aqueous stability assessed as time to reach 90% of starting dose at pH 72008Journal of medicinal chemistry, Apr-24, Volume: 51, Issue:8
Prodrugs of phosphates and phosphonates.
AID344057Reduction in blood glucose level in Sprague-Dawley rat assessed as time of maximum glucose lowering at 30 mg/kg, po2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors.
AID597864Antidiabetic activity in db/db C57BLKS mouse assessed as reduction of plasma glucose level at 200 mg/kg, po administered 4 hrs after food removal measured after 6 hrs postdose (Rbv = 23.84 +/- 0.98 mM)2011Bioorganic & medicinal chemistry letters, Jun-01, Volume: 21, Issue:11
Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase.
AID344059Drug uptake in cryopreserved human hepatocytes per million cells at 100 uM after 60 mins2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors.
AID328940Metabolic stability in rat liver S9 fraction assessed as esterase conversion rate2008Journal of medicinal chemistry, Apr-24, Volume: 51, Issue:8
Prodrugs of phosphates and phosphonates.
AID328939Aqueous stability assessed as time to reach 90% of starting dose at pH 3.0 to 7.42008Journal of medicinal chemistry, Apr-24, Volume: 51, Issue:8
Prodrugs of phosphates and phosphonates.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (14)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's7 (50.00)29.6817
2010's7 (50.00)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: 11.68

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 Index11.68 (24.57)
Research Supply Index2.71 (2.92)
Research Growth Index4.39 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.68)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews2 (14.29%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other12 (85.71%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
lactic acid
Lactic Acid: A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed). 2-hydroxypropanoic acid : A 2-hydroxy monocarboxylic acid that is propanoic acid in which one of the alpha-hydrogens is replaced by a hydroxy group.		2.74302-hydroxy monocarboxylic acidalgal metabolite;
Daphnia magna metabolite
metformin
Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.		2.0510guanidinesenvironmental contaminant;
geroprotector;
hypoglycemic agent;
xenobiotic
alanine
Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.. alanine : An alpha-amino acid that consists of propionic acid bearing an amino substituent at position 2.		5.36100alanine zwitterion;
alanine;
L-alpha-amino acid;
proteinogenic amino acid;
pyruvate family amino acid		EC 4.3.1.15 (diaminopropionate ammonia-lyase) inhibitor;
fundamental metabolite
adenosine monophosphate
Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.		2.0210adenosine 5'-phosphate;
purine ribonucleoside 5'-monophosphate		adenosine A1 receptor agonist;
cofactor;
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
EC 3.1.3.11 (fructose-bisphosphatase) inhibitor;
fundamental metabolite;
micronutrient;
nutraceutical
thiazoles
[no description available]		2.97401,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
fructose-6-phosphate
fructose-6-phosphate: RN given refers to parent cpd with unspecified isomeric designation. fructose 6-phosphate : A ketohexose monophosphate consisting of fructose having a phosphate group located at the 6-position.		2.0410D-fructose 6-phosphate
cgs 25462
CGS 25462: a neutral endopeptidase (NEP) inhibitor; structure given in first source		2.0410
organophosphonates
hydrogenphosphite : A divalent inorganic anion resulting from the removal of a proton from two of the hydroxy groups of phosphorous acid.		5.36100divalent inorganic anion;
phosphite ion
gs-7340
tenofovir alafenamide: component of Biktarvy. tenofovir alafenamide : An L-alanine derivative that is isopropyl L-alaninate in which one of the amino hydrogens is replaced by an (S)-({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)(phenoxy)phosphoryl group. A prodrug for tenofovir, it is used (as the fumarate salt) in combination therapy for the treatment of HIV-1 infection.		2.44206-aminopurines;
ether;
isopropyl ester;
L-alanine derivative;
phosphoramidate ester		antiviral drug;
HIV-1 reverse transcriptase inhibitor;
prodrug
cp 91149
CP 91149: inhibits liver glycogen phosphorylase; structure in first source		2.0610
mb 05032
[no description available]		2.4620
fructose-1,6-diphosphate
fructose-1,6-diphosphate: RN refers to (D)-isomer		2.0410
ConditionIndicatedRelationship StrengthStudiesTrials
Diabetes Mellitus, Adult-Onset
[description not available]		05.22110
Diabetes Mellitus, Type 2
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.		05.22110
Alloxan Diabetes
[description not available]		02.0610
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.0610
Hyperglycemia, Postprandial
Abnormally high BLOOD GLUCOSE level after a meal.		02.4420
Hyperglycemia
Abnormally high BLOOD GLUCOSE level.		02.4420
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		02.0310