Page last updated: 2024-11-13

cr4056

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

Cross-References

ID Source	ID
PubMed CID	24898732
CHEMBL ID	2179398
SCHEMBL ID	936291
MeSH ID	M000604701

Synonyms (20)

Synonym
CHEMBL2179398
bdbm113058
us8633208, 1
6-(1h-imidazol-1-yl)-2-phenylquinazoline
CSZGXYBGYFNSCO-UHFFFAOYSA-N
SCHEMBL936291
1004997-71-0
cr4056
CS-8107
HY-100179
quinazoline, 6-(1h-imidazol-1-yl)-2-phenyl-
w9sq1x2npz ,
unii-w9sq1x2npz
2-phenyl-6-(1h-imidazol-1-yl)quinazoline
gtpl10453
6-imidazol-1-yl-2-phenylquinazoline
cr-4056
EX-A7657
DTXSID301274308
AKOS040741573

Research Excerpts

Overview

CR4056 is a novel imidazoline-2 (I2 ) ligand exhibiting potent analgesic activity in animal models of pain. It is under development for postoperative pain both as stand-alone treatment and in association with morphine.

Excerpt	Reference	Relevance
"CR4056 is a first-in-class imidazoline-2 (I"	( CR4056, a powerful analgesic imidazoline-2 receptor ligand, inhibits the inflammation-induced PKCε phosphorylation and membrane translocation in sensory neurons. Caselli, G; Giacomoni, C; Lanza, M; Letari, O; Milia, C; Rovati, LC; Sabatini, C; Vellani, V, 2020)	3.44
"CR4056 is a selective imidazoline-2 (I2) receptor ligand with potent analgesic activity in animal pain models. "	( Efficacy and safety of the first-in-class imidazoline-2 receptor ligand CR4056 in pain from knee osteoarthritis and disease phenotypes: a randomized, double-blind, placebo-controlled phase 2 trial. Blicharski, T; Bonazzi, A; Brambilla, N; Connell, J; D'Amato, M; Giacovelli, G; Girolami, F; Rovati, LC; Vitalini, C, 2020)	2.23
"CR4056 is a novel imidazoline-2 (I2 ) ligand exhibiting potent analgesic activity in animal models of pain. "	( Modulation of imidazoline I2 binding sites by CR4056 relieves postoperative hyperalgesia in male and female rats. Caselli, G; Ferrari, F; Lanza, M; Menghetti, I; Tremolada, D, 2014)	2.1
"CR4056 is a novel pharmacological agent under development for postoperative pain both as stand-alone treatment and in association with morphine. "	( Modulation of imidazoline I2 binding sites by CR4056 relieves postoperative hyperalgesia in male and female rats. Caselli, G; Ferrari, F; Lanza, M; Menghetti, I; Tremolada, D, 2014)	2.1

Toxicity

Excerpt	Reference	Relevance
"Prolonged use of opioids causes analgesic tolerance and adverse effects including constipation and dependence."	( Improved efficacy, tolerance, safety, and abuse liability profile of the combination of CR4056 and morphine over morphine alone in rodent models. Bonazzi, A; Borsi Franchini, M; Caselli, G; Comi, E; Ferrari, F; Lanza, M; Milia, C; Rovati, LC; Sabatini, C; Sala, E, 2020)	0.78
" Opioid-induced adverse effects were assessed in rodent models of morphine-induced constipation, sedation (open field, sedation rating scale, and rotarod), physical dependence (naloxone-induced withdrawal), and abuse (conditioned place preference-associated reward)."	( Improved efficacy, tolerance, safety, and abuse liability profile of the combination of CR4056 and morphine over morphine alone in rodent models. Bonazzi, A; Borsi Franchini, M; Caselli, G; Comi, E; Ferrari, F; Lanza, M; Milia, C; Rovati, LC; Sabatini, C; Sala, E, 2020)	0.78

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

Bioassays (8)

Assay ID	Title	Year	Journal	Article
AID1561258	Displacement of [3H]RX821002 from alpha2-AR in human brain frontal cortex incubated for 30 mins by liquid scintillation spectrometry	2020	Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7	Bicyclic α-Iminophosphonates as High Affinity Imidazoline I
AID1561256	Displacement of [3H]2-BFI from I2IR in Wistar rat brain cortex incubated for 90 mins by radioligand binding assay	2020	Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7	Bicyclic α-Iminophosphonates as High Affinity Imidazoline I
AID1561262	Displacement of [3H]2-BFI from I2IR in human brain frontal cortex assessed as binding affinity at low affinity site incubated for 45 mins by liquid scintillation spectrometry	2020	Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7	Bicyclic α-Iminophosphonates as High Affinity Imidazoline I
AID1561261	Displacement of [3H]2-BFI from I2IR in human brain frontal cortex assessed as binding affinity at high affinity site incubated for 45 mins by liquid scintillation spectrometry	2020	Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7	Bicyclic α-Iminophosphonates as High Affinity Imidazoline I
AID1561263	Displacement of [3H]2-BFI from I2IR in human brain frontal cortex assessed as binding affinity at high affinity site incubated for 45 mins by liquid scintillation spectrometry relative to control	2020	Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7	Bicyclic α-Iminophosphonates as High Affinity Imidazoline I
AID1561310	Selectivity ratio of Ki for alpha2-AR high binding site in human brain frontal cortex to Ki for I2IR high binding site in human brain frontal cortex	2020	Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7	Bicyclic α-Iminophosphonates as High Affinity Imidazoline I
AID710412	Displacement of [3H]idazoxan from rat cerebral cortex imidazole receptor 2 at 10 uM in presence of 1 uM yohimbine	2012	Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22	Identification of small molecule inhibitors of amyloid β-induced neuronal apoptosis acting through the imidazoline I(2) receptor.
AID710419	Displacement of [3H]2-BFI from rat imidazole receptor 2 in rat whole brain at 10 uM in presence of 1 uM yohimbine	2012	Journal of medicinal chemistry, Nov-26, Volume: 55, Issue:22	Identification of small molecule inhibitors of amyloid β-induced neuronal apoptosis acting through the imidazoline I(2) receptor.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (12)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	6 (50.00)	24.3611
2020's	6 (50.00)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 19.57

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 moderate demand-to-supply ratio for research on this compound.

Metric	This Compound (vs All)
Research Demand Index	19.57 (24.57)
Research Supply Index	2.64 (2.92)
Research Growth Index	4.57 (4.65)
Search Engine Demand Index	15.26 (26.88)
Search Engine Supply Index	2.00 (0.95)

This Compound (19.57)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	1 (8.33%)	5.53%
Reviews	0 (0.00%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	11 (91.67%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
bu 224 BU 224: a selective imidazoline 2-receptor blocker	2.52	2	0	quinolines
memantine [no description available]	2.07	1	0	adamantanes; primary aliphatic amine	antidepressant; antiparkinson drug; dopaminergic agent; neuroprotective agent; NMDA receptor antagonist
methadone Methadone: A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3). methadone : A racemate comprising equimolar amounts of dextromethadone and levomethadone. It is a opioid analgesic which is used as a painkiller and as a substitute for heroin in the treatment of heroin addiction.. 6-(dimethylamino)-4,4-diphenylheptan-3-one : A ketone that is heptan-3-one substituted by a dimethylamino group at position 6 and two phenyl groups at position 4.	2.1	1	0	benzenes; diarylmethane; ketone; tertiary amino compound
moxonidine moxonidine: structure given in first source	2.25	1	0	organohalogen compound; pyrimidines
reserpine Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.. reserpine : An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria.	2.21	1	0	alkaloid ester; methyl ester; yohimban alkaloid	adrenergic uptake inhibitor; antihypertensive agent; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; first generation antipsychotic; plant metabolite; xenobiotic
yohimbine Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.. yohimbine : An indole alkaloid with alpha2-adrenoceptor antagonist activity. It is produced by Corynanthe johimbe and Rauwolfia serpentina.	2.1	1	0	methyl 17-hydroxy-20xi-yohimban-16-carboxylate	alpha-adrenergic antagonist; dopamine receptor D2 antagonist; serotonergic antagonist
quinazolines Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives.	5.17	9	1	azaarene; mancude organic heterobicyclic parent; ortho-fused heteroarene; quinazolines
idazoxan Idazoxan: A benzodioxane-linked imidazole that has alpha-2 adrenoceptor antagonist activity.. idazoxan : A benzodioxine that is 2,3-dihydro-1,4-benzodioxine in which one of the hydrogens at position 2 has been replaced by a 4,5-dihydro-1H-imidazol-2-yl group.	2.86	3	0	benzodioxine; imidazolines	alpha-adrenergic antagonist
efaroxan efaroxan: RN given refers to parent cpd	2.1	1	0	1-benzofurans
1,2,3,4-tetrahydro-1-phenylisoquinoline 1,2,3,4-tetrahydro-1-phenylisoquinoline: structure in first source	2.07	1	0
benzofurans Benzofurans: Compounds that contain a BENZENE ring fused to a furan ring.	3.04	4	0
2-(2-benzofuranyl)-2-imidazoline 2-(2-benzofuranyl)-2-imidazoline: structure given in first source	3.07	4	0	benzofurans
naloxone Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.. naloxone : A synthetic morphinane alkaloid that is morphinone in which the enone double bond has been reduced to a single bond, the hydrogen at position 14 has been replaced by a hydroxy group, and the methyl group attached to the nitrogen has been replaced by an allyl group. A specific opioid antagonist, it is used (commonly as its hydrochloride salt) to reverse the effects of opioids, both following their use of opioids during surgery and in cases of known or suspected opioid overdose.	2.1	1	0	morphinane alkaloid; organic heteropentacyclic compound; tertiary alcohol	antidote to opioid poisoning; central nervous system depressant; mu-opioid receptor antagonist
morphine Meconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn.	7.82	3	0	morphinane alkaloid; organic heteropentacyclic compound; tertiary amino compound	anaesthetic; drug allergen; environmental contaminant; geroprotector; mu-opioid receptor agonist; opioid analgesic; plant metabolite; vasodilator agent; xenobiotic
dizocilpine maleate Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.. dizocilpine maleate : A maleate salt obtained by reaction of dizocilpine with one equivalent of maleic acid.	2.07	1	0	maleate salt; tetracyclic antidepressant	anaesthetic; anticonvulsant; neuroprotective agent; nicotinic antagonist; NMDA receptor antagonist
tracizoline tracizoline: RN given for (R-(R,R))-2,3-dihydroxybutanedionate (1:1); ligand for imidazoline receptor; structure in first source	2.55	2	0
2-(4,5-dihydro-1h-imidazol-2-yl)-1-methyl-1h-indole 2-(4,5-dihydro-1H-imidazol-2-yl)-1-methyl-1H-indole: PET imaging agent for the Imidazoline2 binding site; structure in first source	2.25	1	0

Condition	Relationship Strength	Studies	Trials
Acute Confusional Senile Dementia [description not available]	2.87	3	0
Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)	2.87	3	0
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	2.9	3	0
Depression, Involutional Form of depression in those MIDDLE AGE with feelings of ANXIETY.	2.6	1	0
Depressive Disorder, Major Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5)	2.6	1	0
Innate Inflammatory Response [description not available]	2.25	1	0
Ache [description not available]	2.88	3	0
Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	7.25	1	0
Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.	2.88	3	0
Joint Pain [description not available]	3.64	1	1
Osteoarthritis of Knee [description not available]	3.64	1	1
Arthralgia Pain in the joint.	3.64	1	1
Osteoarthritis, Knee Noninflammatory degenerative disease of the knee joint consisting of three large categories: conditions that block normal synchronous movement, conditions that produce abnormal pathways of motion, and conditions that cause stress concentration resulting in changes to articular cartilage. (Crenshaw, Campbell's Operative Orthopaedics, 8th ed, p2019)	3.64	1	1
Diffuse Myofascial Pain Syndrome [description not available]	2.21	1	0
Allodynia [description not available]	2.54	2	0
Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders.	2.21	1	0
Fibromyalgia A common nonarticular rheumatic syndrome characterized by myalgia and multiple points of focal muscle tenderness to palpation (trigger points). Muscle pain is typically aggravated by inactivity or exposure to cold. This condition is often associated with general symptoms, such as sleep disturbances, fatigue, stiffness, HEADACHES, and occasionally DEPRESSION. There is significant overlap between fibromyalgia and the chronic fatigue syndrome (FATIGUE SYNDROME, CHRONIC). Fibromyalgia may arise as a primary or secondary disease process. It is most frequent in females aged 20 to 50 years. (From Adams et al., Principles of Neurology, 6th ed, p1494-95)	2.21	1	0
Acute Post-operative Pain [description not available]	2.1	1	0
Pain, Postoperative Pain during the period after surgery.	2.1	1	0

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