Page last updated: 2024-12-11

t-226296

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

Description

T-226296: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID Source	ID
PubMed CID	9865843
CHEMBL ID	178707
SCHEMBL ID	5582818
MeSH ID	M0428509

Synonyms (21)

Synonym
n-(6-((dimethylamino)methyl)-5,6,7,8-tetrahydronaphthalen-2-yl)-4''-fluorobiphenyl-4-carboxamide
bdbm50150715
4''-fluoro-biphenyl-4-carboxylic acid (6-dimethylaminomethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-amide
4''''-fluoro-biphenyl-4-carboxylic acid (6-dimethylaminomethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-amide
gtpl1314
t226296
n-[6-(dimethylaminomethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-4-(4-fluorophenyl)benzamide
t 226296
PDSP2_000965
t-226296
PDSP1_000981 ,
CHEMBL178707 ,
GXAQELJVODWLDD-UHFFFAOYSA-N
4'-fluoro-n-[6-[(n,n-dimethylamino)methyl]-5,6,7,8-tetrahydro-2-naphthalenyl][1,1'-biphenyl]-4-carboxamide
4'-fluoro-n-[6-[(n,n-dimethylamino)methyl]-5,6,7,8-tetrahydro-2-naphthalenyl)[1,1'-biphenyl]-4-carboxamide
SCHEMBL5582818
n-(6-((dimethylamino)methyl)-5,6,7,8-tetrahydronaphthalen-2-yl)-4'-fluoro-[1,1'-biphenyl]-4-carboxamide
331758-35-1
Q27088915
n-[6-[(dimethylamino)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]-4-(4-fluorophenyl)benzamide
AKOS040749598

Research Excerpts

Bioavailability

Excerpt	Reference	Relevance
" We attempted to replicate the effects previously reported with SNAP-7941 and expanded the investigation to three other orally bioavailable MCH-1 receptor antagonists with good brain penetration."	( Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety. Basso, AM; Bratcher, NA; Brune, ME; Collins, CA; Cowart, MD; Esbenshade, TA; Fox, GB; Gallagher, KB; Hancock, AA; Iyengar, R; Kym, PR; Rueter, LE; Schmidt, M; Souers, AJ; Sun, M; Vasudevan, A; Zhao, C, 2006)	0.33
" Pharmacokinetic analysis confirmed that 2s had good oral bioavailability and brain penetrance."	( Discovery, synthesis, and structure-activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists. Asami, A; Endo, S; Imaeda, T; Ishihara, Y; Kamata, M; Kato, K; Miyamoto, M; Nagisa, Y; Nakano, Y; Ogino, H; Ora, T; Suzuki, N; Takekawa, S; Tanaka, T; Tawada, M; Terauchi, J; Watanabe, K; Yamashita, T, 2011)	0.37

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Melanin-concentrating hormone receptor 1	Rattus norvegicus (Norway rat)	IC50 (µMol)	0.0240	0.0240	0.0240	0.0240	AID614322
Melanin-concentrating hormone receptor 1	Homo sapiens (human)	IC50 (µMol)	0.1172	0.0005	0.2363	3.5000	AID242077; AID242643; AID248949; AID353587; AID443384; AID551220; AID614320; AID614321; AID630087
Melanin-concentrating hormone receptor 1	Homo sapiens (human)	Ki	0.0217	0.0028	0.0154	0.0380	AID239711; AID307524
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (8)

Process	via Protein(s)	Taxonomy
generation of precursor metabolites and energy	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
cell surface receptor signaling pathway	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
G protein-coupled receptor signaling pathway	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
positive regulation of cytosolic calcium ion concentration	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
feeding behavior	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
positive regulation of calcium ion transport	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
neuropeptide signaling pathway	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (6)

Process	via Protein(s)	Taxonomy
signaling receptor binding	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
neuropeptide receptor activity	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
melanin-concentrating hormone receptor activity	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
hormone binding	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
G protein-coupled receptor activity	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
neuropeptide binding	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Process	via Protein(s)	Taxonomy
plasma membrane	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
cilium	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
ciliary membrane	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
non-motile cilium	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
neuron projection	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
plasma membrane	Melanin-concentrating hormone receptor 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (16)

Assay ID	Title	Year	Journal	Article
AID1346168	Human MCH1 receptor (Melanin-concentrating hormone receptors)	2002	European journal of pharmacology, Mar-08, Volume: 438, Issue:3	T-226296: a novel, orally active and selective melanin-concentrating hormone receptor antagonist.
AID614320	Displacement of [125I]-MCH from human MCHR1 expressed in CHO cells after 60 mins by scintillation counting	2011	Bioorganic & medicinal chemistry, Sep-15, Volume: 19, Issue:18	Discovery, synthesis, and structure-activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists.
AID551401	Suppression of spontaneous food intake in diet-induced obese C57BL/6 mouse model at 30 mg/kg, po after 24 hrs	2011	Bioorganic & medicinal chemistry, Jan-15, Volume: 19, Issue:2	Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists.
AID630087	Displacement of [125I]-MCH(4-19) from human MCHR1 expressed in CHO cells	2011	Bioorganic & medicinal chemistry, Nov-01, Volume: 19, Issue:21	Melanin-concentrating hormone receptor 1 antagonists: synthesis, structure-activity relationship, docking studies, and biological evaluation of 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives.
AID614321	Antagonist activity at human MCHR1 expressed in CHO cells assessed as inhibition of MCH-induced GTPgammaS binding after 60 mins by scintillation counting	2011	Bioorganic & medicinal chemistry, Sep-15, Volume: 19, Issue:18	Discovery, synthesis, and structure-activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists.
AID239711	Displacement of [125I]MCH from human Melanin-concentrating hormone 1 (MCH1) receptor modified for optimal expression in HEK293 cells	2005	Bioorganic & medicinal chemistry letters, Feb-15, Volume: 15, Issue:4	Bis(aminopyrrolidine)-derived ureas (APUs) as potent MCH1 receptor antagonists.
AID614322	Displacement of [125I]-MCH from rat MCHR1 expressed in CHO cells after 60 mins by scintillation counting	2011	Bioorganic & medicinal chemistry, Sep-15, Volume: 19, Issue:18	Discovery, synthesis, and structure-activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists.
AID242077	Inhibition of Melanin-concentrating hormone 1 receptor expressed in CHO cells	2004	Journal of medicinal chemistry, Jul-29, Volume: 47, Issue:16	A virtual screening approach to finding novel and potent antagonists at the melanin-concentrating hormone 1 receptor.
AID242643	Concentration required to inhibit binding of [125I]-MCH radioligand to human Melanin-concentrating hormone receptor 1 in IMR-32 I3.4.2 cell membranes	2004	Bioorganic & medicinal chemistry letters, Oct-04, Volume: 14, Issue:19	Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 2.
AID248949	Concentration required to inhibit 50% of melanin-concentrating hormone induced [Ca2+] flux in IMR-32 cells measured by using a fluorometric imaging plate reader	2004	Bioorganic & medicinal chemistry letters, Oct-04, Volume: 14, Issue:19	Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 2.
AID252268	Suppression of Melanin concentrating hormone receptor-stimulated food intake in lean rats after 30 mg/kg dose	2005	Journal of medicinal chemistry, Apr-07, Volume: 48, Issue:7	Discovery of bicycloalkyl urea melanin concentrating hormone receptor antagonists: orally efficacious antiobesity therapeutics.
AID307524	Displacement of [125I][Phe13, Tyr19]MCH from human recombinant MCHR1 expressed in CHO cells	2007	Bioorganic & medicinal chemistry letters, Jul-01, Volume: 17, Issue:13	Design and synthesis of novel hydantoin-containing melanin-concentrating hormone receptor antagonists.
AID443384	Antagonist activity at CART form of human MCH1 receptor expressed in HEK293 cells coexpressing Galphaq assessed as inhibition of MCH-induced intracellular calcium level by FLIPR assay	2009	Bioorganic & medicinal chemistry letters, Nov-01, Volume: 19, Issue:21	Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation.
AID551220	Displacement of [125I]MCH from human MCHR1 expressed in CHO cells by competition binding assay	2011	Bioorganic & medicinal chemistry, Jan-15, Volume: 19, Issue:2	Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists.
AID614324	Antiobesity activity in KKAy mouse assessed as inhibition of food intake at 30 mg/kg, po after 2 hrs	2011	Bioorganic & medicinal chemistry, Sep-15, Volume: 19, Issue:18	Discovery, synthesis, and structure-activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists.
AID353587	Antagonist activity at MCH1R by [35S]GTPgammaS binding assay	2009	Journal of medicinal chemistry, Apr-09, Volume: 52, Issue:7	Novel approach for chemotype hopping based on annotated databases of chemically feasible fragments and a prospective case study: new melanin concentrating hormone antagonists.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (16)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	12 (75.00)	29.6817
2010's	4 (25.00)	24.3611
2020's	0 (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: 11.49

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.

Metric	This Compound (vs All)
Research Demand Index	11.49 (24.57)
Research Supply Index	2.83 (2.92)
Research Growth Index	4.32 (4.65)
Search Engine Demand Index	0.00 (26.88)
Search Engine Supply Index	0.00 (0.95)

This Compound (11.49)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	1 (6.25%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	15 (93.75%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
imipramine Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.. imipramine : A dibenzoazepine that is 5H-dibenzo[b,f]azepine substituted by a 3-(dimethylamino)propyl group at the nitrogen atom.	2.03	1	dibenzoazepine	adrenergic uptake inhibitor; antidepressant; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor
sibutramine sibutramine: serotonin and norepinephrine transporter inhibitor; Meridia is tradename for sibutramine hydrochloride	2.44	2	organochlorine compound; tertiary amino compound	anti-obesity agent; serotonin uptake inhibitor
indazoles Indazoles: A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.	2.03	1	indazole
1-(3-(4-chlorobenzoyl)propyl)-4-hydroxy-4-(4-chlorophenyl)piperidine 1-(3-(4-chlorobenzoyl)propyl)-4-hydroxy-4-(4-chlorophenyl)piperidine: RN given refers to parent cpd	2.02	1
arachidonic acid icosa-5,8,11,14-tetraenoic acid : Any icosatetraenoic acid with the double bonds at positions 5, 8, 11 and 14.. arachidonate : A long-chain fatty acid anion resulting from the removal of a proton from the carboxy group of arachidonic acid.	2.01	1	icosa-5,8,11,14-tetraenoic acid; long-chain fatty acid; omega-6 fatty acid	Daphnia galeata metabolite; EC 3.1.1.1 (carboxylesterase) inhibitor; human metabolite; mouse metabolite
11-cis-retinal Rhodopsin: A purplish-red, light-sensitive pigment found in RETINAL ROD CELLS of most vertebrates. It is a complex consisting of a molecule of ROD OPSIN and a molecule of 11-cis retinal (RETINALDEHYDE). Rhodopsin exhibits peak absorption wavelength at about 500 nm.. 11-cis-retinal : A retinal having 2E,4Z,6E,8E-double bond geometry.	2.02	1	retinal	chromophore; human metabolite; mouse metabolite
gw 803430 [no description available]	2.45	2
n-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3,4-difluorobenzamide hydrochloride [no description available]	2.44	2
snap7941 SNAP7941: structure in first source	4.23	5
piperidines Piperidines: A family of hexahydropyridines.	3.83	3
guanosine 5'-o-(3-thiotriphosphate) Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.	2.01	1	nucleoside triphosphate analogue

Condition	Relationship Strength	Studies
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).	4.05	5
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	2.44	2
Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders.	2.03	1
Weight Reduction [description not available]	2.05	1
Weight Loss Decrease in existing BODY WEIGHT.	2.05	1
Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	3.34	2
Depression, Endogenous [description not available]	2.03	1
Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.	2.03	1
Depressive Disorder An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.	2.03	1

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