Compounds > ml 00253764
Page last updated: 2024-11-11

ml 00253764

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

Description

2-(2-(2-(5-bromo-2-methoxyphenyl)ethyl)-3-fluorophenyl)-4,5-dihydro-1H-imidazole: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9842665
CHEMBL ID40711
SCHEMBL ID3728758
MeSH IDM0465584

Synonyms (16)

Synonym
ml-00253764
bdbm50142895
2-{2-[2-(5-bromo-2-methoxy-phenyl)-ethyl]-3-fluoro-phenyl}-4,5-dihydro-1h-imidazole
2-(2-(5-bromo-2-methoxyphenethyl)-3-fluorophenyl)-4,5-dihydro-1h-imidazole
CHEMBL40711 ,
ml-253764
SCHEMBL3728758
2-[2-[2-(5-bromo-2-methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1h-imidazole
unii-ee3s6557v5
ml00253764
ee3s6557v5 ,
1h-imidazole, 2-(2-(2-(5-bromo-2-methoxyphenyl)ethyl)-3-fluorophenyl)-4,5-dihydro-
2-(2-(2-(5-bromo-2-methoxyphenyl)ethyl)-3-fluorophenyl)-4,5-dihydro-1h-imidazole
CS-0087524
HY-124740
AKOS040745239

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic properties of these MC4R antagonists, including brain penetration, were studied in mice after oral and intravenous administrations."( Pharmacological and pharmacokinetic characterization of 2-piperazine-alpha-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists.
Arellano, M; Bozigian, H; Chen, C; Chen, CW; Chen, T; Fleck, BA; Foster, AC; Harman, J; Hoare, SR; Jiang, W; Johns, M; Marinkovic, D; Markison, S; Marks, D; Saunders, J; Tran, JA; Tucci, FC; Wen, J, 2008)		0.35

Compound-Compound Interactions

ExcerptReferenceRelevance
" Proliferation, cell cycle, and apoptotic assays were performed with ML00253764, whereas the synergism of the simultaneous combination with temozolomide was evaluated by the combination index method."( Melanocortin Receptor-4 and Glioblastoma Cells: Effects of the Selective Antagonist ML00253764 Alone and in Combination with Temozolomide In Vitro and In Vivo.
Bocci, G; Di Desidero, T; Giuliani, D; Guarini, S; Orlandi, P; Ottani, A; Pacini, S; Pardini, C; Pasqualetti, F; Vaglini, F, 2018)		0.48

Dosage Studied

ExcerptRelevanceReference
" Similar in vivo effects were also observed when 11d was dosed orally at 20mg/kg."( Pharmacological and pharmacokinetic characterization of 2-piperazine-alpha-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists.
Arellano, M; Bozigian, H; Chen, C; Chen, CW; Chen, T; Fleck, BA; Foster, AC; Harman, J; Hoare, SR; Jiang, W; Johns, M; Marinkovic, D; Markison, S; Marks, D; Saunders, J; Tran, JA; Tucci, FC; Wen, J, 2008)		0.35
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Melanocortin receptor 4Homo sapiens (human)IC50 (µMol)1.79200.00020.64136.1900AID259554; AID259555; AID259556; AID259557; AID259558; AID259559; AID259560; AID259561; AID259562; AID259563; AID407583; AID407584
Melanocortin receptor 4Homo sapiens (human)Ki0.92010.00000.30864.8860AID239362; AID259534; AID259535; AID259536; AID259537; AID259538; AID259539; AID259540; AID259541; AID259542; AID259543
Melanocortin receptor 4Mus musculus (house mouse)Ki0.16000.16000.16000.1600AID109286
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (13)

Processvia Protein(s)Taxonomy
diet induced thermogenesisMelanocortin receptor 4Homo sapiens (human)
energy reserve metabolic processMelanocortin receptor 4Homo sapiens (human)
adenylate cyclase-modulating G protein-coupled receptor signaling pathwayMelanocortin receptor 4Homo sapiens (human)
adenylate cyclase-activating G protein-coupled receptor signaling pathwayMelanocortin receptor 4Homo sapiens (human)
feeding behaviorMelanocortin receptor 4Homo sapiens (human)
insulin secretionMelanocortin receptor 4Homo sapiens (human)
response to insulinMelanocortin receptor 4Homo sapiens (human)
positive regulation of bone resorptionMelanocortin receptor 4Homo sapiens (human)
regulation of eating behaviorMelanocortin receptor 4Homo sapiens (human)
response to melanocyte-stimulating hormoneMelanocortin receptor 4Homo sapiens (human)
negative regulation of feeding behaviorMelanocortin receptor 4Homo sapiens (human)
regulation of grooming behaviorMelanocortin receptor 4Homo sapiens (human)
regulation of metabolic processMelanocortin receptor 4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (6)

Processvia Protein(s)Taxonomy
melanocortin receptor activityMelanocortin receptor 4Homo sapiens (human)
melanocyte-stimulating hormone receptor activityMelanocortin receptor 4Homo sapiens (human)
protein bindingMelanocortin receptor 4Homo sapiens (human)
peptide hormone bindingMelanocortin receptor 4Homo sapiens (human)
ubiquitin protein ligase bindingMelanocortin receptor 4Homo sapiens (human)
neuropeptide bindingMelanocortin receptor 4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (3)

Processvia Protein(s)Taxonomy
plasma membraneMelanocortin receptor 4Homo sapiens (human)
membraneMelanocortin receptor 4Homo sapiens (human)
plasma membraneMelanocortin receptor 4Homo sapiens (human)
cytoplasmMelanocortin receptor 4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (30)

Assay IDTitleYearJournalArticle
AID259539Displacement of [125I]NDP-alpha-MSH from mutant MC4R F184A expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259540Displacement of [125I]NDP-alpha-MSH from mutant MC4R F184L expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID407583Binding affinity at MC4R2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Pharmacological and pharmacokinetic characterization of 2-piperazine-alpha-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists.
AID259554Antagonist activity at the human wild type MC4R expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID11431Cmax in rat at the dose of 1 mg/kg i.v.2004Bioorganic & medicinal chemistry letters, Jul-16, Volume: 14, Issue:14
Synthesis and biological evaluation of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R).
AID259556Antagonist activity at the mutant MC4R Y268F expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259534Displacement of [125I]NDP-alpha-MSH from human wild type MC4R expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259561Antagonist activity at the mutant MC4R I125A expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259537Displacement of [125I]NDP-alpha-MSH from mutant MC4R Y287A expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259560Antagonist activity at the mutant MC4R F184L expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259558Antagonist activity at the mutant MC4R Y287F expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID109286Antagonistic activity against mice melanocortin 4 receptor using [125I][NDP]-R-MSH as radioligand in a membrane filtration assay2004Journal of medicinal chemistry, Mar-25, Volume: 47, Issue:7
Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model.
AID259543Displacement of [125I]NDP-alpha-MSH from mutant MC4R I291A expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID263805Oral bioavailability in rat2006Bioorganic & medicinal chemistry letters, Apr-15, Volume: 16, Issue:8
Identification and structure-activity relationships of a new series of Melanocortin-4 receptor antagonists.
AID259555Antagonist activity at the mutant MC4R Y268A expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259538Displacement of [125I]NDP-alpha-MSH from mutant MC4R Y287F expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID239362Binding affinity for melanocortin-4 receptor transfected in HEK 293 cells using [125I]NDP-MSH as radioligand2005Bioorganic & medicinal chemistry letters, May-16, Volume: 15, Issue:10
A potent and selective nonpeptide antagonist of the melanocortin-4 receptor induces food intake in satiated mice.
AID259562Antagonist activity at the mutant MC4R I125L expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID114584Functional antagonism measured by inhibition of cAMP production induced by [NDP]-R-MSH in a whole cell assay in mice at a dose of 30mg/kg, sc for 6 hr2004Journal of medicinal chemistry, Mar-25, Volume: 47, Issue:7
Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model.
AID259563Antagonist activity at the mutant MC4R I291A expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID263806Plasma half life in iv dosed rat2006Bioorganic & medicinal chemistry letters, Apr-15, Volume: 16, Issue:8
Identification and structure-activity relationships of a new series of Melanocortin-4 receptor antagonists.
AID15523Plasma clearance was determined2004Bioorganic & medicinal chemistry letters, Jul-16, Volume: 14, Issue:14
Synthesis and biological evaluation of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R).
AID259557Antagonist activity at the mutant MC4R Y287A expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259542Displacement of [125I]NDP-alpha-MSH from mutant MC4R I129A expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID13513AUC was determined2004Bioorganic & medicinal chemistry letters, Jul-16, Volume: 14, Issue:14
Synthesis and biological evaluation of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R).
AID259535Displacement of [125I]NDP-alpha-MSH from mutant MC4R Y268A expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259541Displacement of [125I]NDP-alpha-MSH from mutant MC4R I125A expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID407584Antagonist activity at MC4R2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Pharmacological and pharmacokinetic characterization of 2-piperazine-alpha-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists.
AID259536Displacement of [125I]NDP-alpha-MSH from mutant MC4R Y268F expressed in HEK293 cells2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
AID259559Antagonist activity at the mutant MC4R F184A expressed in HEK293 cells by cAMP accumulation2006Journal of medicinal chemistry, Feb-09, Volume: 49, Issue:3
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (12)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's8 (66.67)29.6817
2010's4 (33.33)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: 11.81

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 Index11.81 (24.57)
Research Supply Index2.56 (2.92)
Research Growth Index4.37 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.81)

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%
Other12 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
temozolomide
[no description available]		2.1710imidazotetrazine;
monocarboxylic acid amide;
triazene derivative		alkylating agent;
antineoplastic agent;
prodrug
alpha-msh
[no description available]		2.0310peptide hormoneanti-inflammatory agent
msh, 4-nle-7-phe-alpha-
[no description available]		2.4620polypeptidedermatologic drug
ConditionIndicatedRelationship StrengthStudiesTrials
Emaciation
Clinical manifestation of excessive LEANNESS usually caused by disease or a lack of nutrition (MALNUTRITION).		02.0210
Benign Neoplasms
[description not available]		02.0210
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		02.0210
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		02.4320
Carcinoma, Lewis Lung
A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.		02.4420
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.0410
Cachexia
General ill health, malnutrition, and weight loss, usually associated with chronic disease.		02.4420
Benign Neoplasms, Brain
[description not available]		02.1710
Astrocytoma, Grade IV
[description not available]		02.1710
Brain Neoplasms
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.		02.1710
Glioblastoma
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.		02.1710
Morbid Obesity
[description not available]		02.110
Obesity, Morbid
The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.		02.110
Obesity
A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).		02.0510