Compounds > n-cyclobutyl-6-((3-fluorophenyl)ethynyl)nicotinamide
Page last updated: 2024-11-13

n-cyclobutyl-6-((3-fluorophenyl)ethynyl)nicotinamide

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

Description

N-cyclobutyl-6-((3-fluorophenyl)ethynyl)nicotinamide: an mGlu5 agonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID53318624
CHEMBL ID1684242
SCHEMBL ID19411346
MeSH IDM0585926

Synonyms (14)

Synonym
CHEMBL1684242 ,
vu0360172
n-cyclobutyl-6-((3-fluorophenyl)ethynyl)nicotinamide
bdbm50337958
n-cyclobutyl-6-[2-(3-fluorophenyl)ethynyl]pyridine-3-carboxamide
gtpl6400
NCGC00379106-01
SCHEMBL19411346
Q27089182
MS-24214
HY-120589
EX-A6246
1310012-12-4
AKOS040749768

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)		0.51

Dosage Studied

ExcerptRelevanceReference
" Consistent with this observation, VU0360172 could also enhance thalamic GAT-1 protein expression, depending on the dosing regimen."( Pharmacological activation of mGlu5 receptors with the positive allosteric modulator VU0360172, modulates thalamic GABAergic transmission.
Bruno, V; Cannella, M; Celli, R; Ciruela, F; Di Menna, L; Mascio, G; Ngomba, RT; Nicoletti, F; Pittaluga, A; Santolini, I; van Luijtelaar, G; Vergassola, M; Wall, MJ, 2020)		0.56
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (3)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency3.37860.01237.983543.2770AID1645841
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Metabotropic glutamate receptor 5Rattus norvegicus (Norway rat)Ki0.19500.00050.19643.7600AID690984
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Metabotropic glutamate receptor 5Rattus norvegicus (Norway rat)EC50 (µMol)0.02750.00151.653710.0000AID690983; AID773845
Metabotropic glutamate receptor 5Homo sapiens (human)EC50 (µMol)0.01600.00190.61454.1000AID578606
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (20)

Processvia Protein(s)Taxonomy
desensitization of G protein-coupled receptor signaling pathwayMetabotropic glutamate receptor 5Homo sapiens (human)
regulation of DNA-templated transcriptionMetabotropic glutamate receptor 5Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathwayMetabotropic glutamate receptor 5Homo sapiens (human)
protein kinase C-activating G protein-coupled receptor signaling pathwayMetabotropic glutamate receptor 5Homo sapiens (human)
phospholipase C-activating G protein-coupled glutamate receptor signaling pathwayMetabotropic glutamate receptor 5Homo sapiens (human)
G protein-coupled glutamate receptor signaling pathwayMetabotropic glutamate receptor 5Homo sapiens (human)
chemical synaptic transmissionMetabotropic glutamate receptor 5Homo sapiens (human)
learning or memoryMetabotropic glutamate receptor 5Homo sapiens (human)
learningMetabotropic glutamate receptor 5Homo sapiens (human)
locomotory behaviorMetabotropic glutamate receptor 5Homo sapiens (human)
positive regulation of MAPK cascadeMetabotropic glutamate receptor 5Homo sapiens (human)
positive regulation of long-term neuronal synaptic plasticityMetabotropic glutamate receptor 5Homo sapiens (human)
synapse organizationMetabotropic glutamate receptor 5Homo sapiens (human)
positive regulation of calcium-mediated signalingMetabotropic glutamate receptor 5Homo sapiens (human)
cognitionMetabotropic glutamate receptor 5Homo sapiens (human)
regulation of postsynaptic membrane potentialMetabotropic glutamate receptor 5Homo sapiens (human)
regulation of postsynaptic cytosolic calcium ion concentrationMetabotropic glutamate receptor 5Homo sapiens (human)
cellular response to amyloid-betaMetabotropic glutamate receptor 5Homo sapiens (human)
regulation of synaptic transmission, glutamatergicMetabotropic glutamate receptor 5Homo sapiens (human)
trans-synaptic signaling by endocannabinoid, modulating synaptic transmissionMetabotropic glutamate receptor 5Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (10)

Processvia Protein(s)Taxonomy
G protein-coupled receptor activityMetabotropic glutamate receptor 5Homo sapiens (human)
protein bindingMetabotropic glutamate receptor 5Homo sapiens (human)
glutamate receptor activityMetabotropic glutamate receptor 5Homo sapiens (human)
protein tyrosine kinase activator activityMetabotropic glutamate receptor 5Homo sapiens (human)
A2A adenosine receptor bindingMetabotropic glutamate receptor 5Homo sapiens (human)
identical protein bindingMetabotropic glutamate receptor 5Homo sapiens (human)
protein tyrosine kinase bindingMetabotropic glutamate receptor 5Homo sapiens (human)
adenylate cyclase inhibiting G protein-coupled glutamate receptor activityMetabotropic glutamate receptor 5Homo sapiens (human)
neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentrationMetabotropic glutamate receptor 5Homo sapiens (human)
G protein-coupled receptor activity involved in regulation of postsynaptic membrane potentialMetabotropic glutamate receptor 5Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (9)

Processvia Protein(s)Taxonomy
dendriteMetabotropic glutamate receptor 5Homo sapiens (human)
cytoplasmMetabotropic glutamate receptor 5Homo sapiens (human)
plasma membraneMetabotropic glutamate receptor 5Homo sapiens (human)
dendritic spineMetabotropic glutamate receptor 5Homo sapiens (human)
dendritic shaftMetabotropic glutamate receptor 5Homo sapiens (human)
astrocyte projectionMetabotropic glutamate receptor 5Homo sapiens (human)
Schaffer collateral - CA1 synapseMetabotropic glutamate receptor 5Homo sapiens (human)
glutamatergic synapseMetabotropic glutamate receptor 5Homo sapiens (human)
postsynaptic density membraneMetabotropic glutamate receptor 5Homo sapiens (human)
plasma membraneMetabotropic glutamate receptor 5Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (13)

Assay IDTitleYearJournalArticle
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID773845Positive allosteric modulation of rat mGluR5 stably expressed in CHO cells assessed as calcium mobilization2013Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20
Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): discovery of 5-((3-fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide
AID690984Displacement of [3H]methoxyPEPy from rat mGluR5 expressed in human HEK293 cells after 1 hr by scintillation counter2012Bioorganic & medicinal chemistry letters, Oct-15, Volume: 22, Issue:20
Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover.
AID578607Positive allosteric modulation of mGlu5 receptor assessed as calcium mobilization at 30 uM relative to glutamate2011Bioorganic & medicinal chemistry letters, Mar-01, Volume: 21, Issue:5
Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold.
AID690983Positive allosteric modulation of rat mGluR5 expressed in human HEK293 cells assessed as calcium mobilization2012Bioorganic & medicinal chemistry letters, Oct-15, Volume: 22, Issue:20
Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover.
AID578606Positive allosteric modulation of mGlu5 receptor assessed as calcium mobilization2011Bioorganic & medicinal chemistry letters, Mar-01, Volume: 21, Issue:5
Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold.
AID773804Ratio of drug level in brain to plasma in (unknown origin)2013Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20
Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): discovery of 5-((3-fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide
AID773805Protein binding in (unknown origin) plasma2013Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20
Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): discovery of 5-((3-fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide
AID1346254Rat mGlu5 receptor (Metabotropic glutamate receptors)2010Molecular pharmacology, Dec, Volume: 78, Issue:6
Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity.
[information is prepared from bioassay 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's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's12 (66.67)24.3611
2020's6 (33.33)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 12.99

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 Index12.99 (24.57)
Research Supply Index3.00 (2.92)
Research Growth Index5.98 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (12.99)

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%
Other19 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
gamma-aminobutyric acid
gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.. gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4.		2.2510amino acid zwitterion;
gamma-amino acid;
monocarboxylic acid		human metabolite;
neurotransmitter;
Saccharomyces cerevisiae metabolite;
signalling molecule
glycine
[no description available]		2.5120alpha-amino acid;
amino acid zwitterion;
proteinogenic amino acid;
serine family amino acid		EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor;
fundamental metabolite;
hepatoprotective agent;
micronutrient;
neurotransmitter;
NMDA receptor agonist;
nutraceutical
niacinamide
nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.		3.93110pyridine alkaloid;
pyridinecarboxamide;
vitamin B3		anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
amphetamine
Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.. 1-phenylpropan-2-amine : A primary amine that is isopropylamine in which a hydrogen attached to one of the methyl groups has been replaced by a phenyl group.. amphetamine : A racemate comprising equimolar amounts of (R)-amphetamine (also known as levamphetamine or levoamphetamine) and (S)-amphetamine (also known as dexamfetamine or dextroamphetamine.		2.1110primary amine
phencyclidine
Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.. phencyclidine : A member of the class of piperidines that is piperidine in which the nitrogen is substituted with a 1-phenylcyclohexyl group. Formerly used as an anaesthetic agent, it exhibits both hallucinogenic and neurotoxic effects.		2.4110benzenes;
piperidines		anaesthetic;
neurotoxin;
NMDA receptor antagonist;
psychotropic drug
oxazoles
Oxazoles: Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.. 1,3-oxazole : A five-membered monocyclic heteroarene that is an analogue of cyclopentadiene with O in place of CH2 at position 1 and N in place of CH at position 3.. oxazole : An azole based on a five-membered heterocyclic aromatic skeleton containing one N and one O atom.		2.41101,3-oxazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
thiazoles
[no description available]		3.02401,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
2-chloro-5-hydroxyphenylglycine
2-chloro-5-hydroxyphenylglycine: activates mGlu(5) receptors; structure in first source		2.0810
am 281
AM 281: radioligand for cannabinoid CB1 receptors; structure in first source		2.0810pyrazoles;
ring assembly
arachidonyl-2-chloroethylamide
arachidonyl-2-chloroethylamide: a potent and selective agonist of the neuronal cannabinoid receptor; structure in first source. arachidonyl-2'-chloroethylamide : A fatty amide obtained by the formal condensation of arachidonic acid with 2-chloroethanamine. It is a potent agonist of the CB1 receptor (Ki = 1.4 nM) and also has a low affinity for the CB2 receptor (Ki = 3100 nM).		2.4920fatty amide;
organochlorine compound;
secondary carboxamide;
synthetic cannabinoid		CB1 receptor agonist;
CB2 receptor agonist;
neuroprotective agent
dinitrofluorobenzene
3,3'-difluorobenzaldazine: a selective positive allosteric modulator of mGluR5 activity; structure in first source		2.0810
n-(4-chloro-2-((1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)methyl)phenyl)-2-hydroxybenzamide
N-(4-chloro-2-((1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl)phenyl)-2-hydroxybenzamide: a positive allosteric modulator of mGluR5; structure in first source		2.0810
3-cyano-n-(1,3-diphenyl-1h-pyrazol-5-yl)benzamide
3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide: affects mGluR5 receptors; structure in first source		2.0810
adx 47273
[no description available]		2.0810
vu0092273
VU0092273: mGlu(5) positive allosteric modulator		2.4920
piperidines
Piperidines: A family of hexahydropyridines.		2.1110
vu0409106
VU0409106: a metabotropic glutamate receptor 5 antagonist; structure in first source		2.1110
vu0424465
[no description available]		2.0810
lsn2463359
[no description available]		2.0810
ConditionIndicatedRelationship StrengthStudiesTrials
Agitation, Psychomotor
[description not available]		02.0510
Psychomotor Agitation
A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.		02.0510
Psychoses
[description not available]		02.0710
Psychotic Disorders
Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)		02.0710
Congenital Zika Syndrome
[description not available]		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		03.0340
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510
Dementia Praecox
[description not available]		02.920
Schizophrenia
A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.		02.920
Encephalopathy, Traumatic
[description not available]		02.3110
Brain Injuries, Traumatic
A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.		02.3110
Autosomal Dominant Cerebellar Ataxia, Type II
[description not available]		02.0810
Spinocerebellar Ataxias
A group of predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)		02.0810
Adjuvant Arthritis
[description not available]		02.110
Ache
[description not available]		02.110
Pain
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.		02.110
Absence Seizure Disorder
[description not available]		02.4920
Epilepsy, Absence
A seizure disorder usually occurring in childhood characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736)		02.4920
Anankastic Personality
[description not available]		02.1310
Obsessive-Compulsive Disorder
An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.		02.1310