Identification

Name
Cimicoxib
Accession Number
DB05095
Type
Small Molecule
Groups
Investigational
Description

Cimicoxib is a selective COX-2 inhibitor being developed by Affectis as a treatment for depression and schizophrenia. If approved, Cimicoxib would be the first drug in decades to treat depression by a new mechanism of action.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
W7FHJ107MC
CAS number
265114-23-6
Weight
Average: 381.809
Monoisotopic: 381.035017899
Chemical Formula
C16H13ClFN3O3S
InChI Key
KYXDNECMRLFQMZ-UHFFFAOYSA-N
InChI
InChI=1S/C16H13ClFN3O3S/c1-24-14-7-2-10(8-13(14)18)15-16(17)20-9-21(15)11-3-5-12(6-4-11)25(19,22)23/h2-9H,1H3,(H2,19,22,23)
IUPAC Name
4-[4-chloro-5-(3-fluoro-4-methoxyphenyl)-1H-imidazol-1-yl]benzene-1-sulfonamide
SMILES
COC1=C(F)C=C(C=C1)C1=C(Cl)N=CN1C1=CC=C(C=C1)S(N)(=O)=O

Pharmacology

Indication

Investigated for use/treatment in depression.

Pharmacodynamics
Not Available
Mechanism of action

Depression and schizophrenia are inflammatory diseases. Increased levels of pro-inflammatory cytokines and prostaglandin E (PGE) have repeatedly been described in major depression. COX-2 inhibitors inhibit production of both. Cimicoxib is a selective COX-2 inhibitor. The mechanism by which some COX-2 inhibitors work in depression could be linked to their anti-inflammatory mechanisms.

TargetActionsOrganism
UProstaglandin G/H synthase 2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when (4R)-limonene is combined with Cimicoxib.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Cimicoxib.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Cimicoxib.
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Cimicoxib.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Cimicoxib is combined with Abciximab.
AcebutololCimicoxib may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Cimicoxib.
AcemetacinThe risk or severity of adverse effects can be increased when Acemetacin is combined with Cimicoxib.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Cimicoxib is combined with Acenocoumarol.
AcetaminophenCimicoxib may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Chegaev K, Lazzarato L, Tosco P, Cena C, Marini E, Rolando B, Carrupt PA, Fruttero R, Gasco A: NO-donor COX-2 inhibitors. New nitrooxy-substituted 1,5-diarylimidazoles endowed with COX-2 inhibitory and vasodilator properties. J Med Chem. 2007 Apr 5;50(7):1449-57. Epub 2007 Mar 3. [PubMed:17335184]
  2. Almansa C, Bartroli J, Belloc J, Cavalcanti FL, Ferrando R, Gomez LA, Ramis I, Carceller E, Merlos M, Garcia-Rafanell J: New water-soluble sulfonylphosphoramidic acid derivatives of the COX-2 selective inhibitor cimicoxib. A novel approach to sulfonamide prodrugs. J Med Chem. 2004 Oct 21;47(22):5579-82. [PubMed:15481993]
External Links
PubChem Compound
213053
PubChem Substance
175426942
ChemSpider
184745
BindingDB
50131593
ChEBI
76127
ChEMBL
CHEMBL435381
Wikipedia
Cimicoxib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentMajor Depressive Disorder (MDD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.018 mg/mLALOGPS
logP3.21ALOGPS
logP2.12ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)10.8ChemAxon
pKa (Strongest Basic)3.69ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area87.21 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity103.72 m3·mol-1ChemAxon
Polarizability35.53 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8514
Caco-2 permeable+0.5426
P-glycoprotein substrateNon-substrate0.8067
P-glycoprotein inhibitor INon-inhibitor0.8166
P-glycoprotein inhibitor IINon-inhibitor0.8338
Renal organic cation transporterNon-inhibitor0.8166
CYP450 2C9 substrateNon-substrate0.6906
CYP450 2D6 substrateNon-substrate0.7202
CYP450 3A4 substrateNon-substrate0.548
CYP450 1A2 substrateNon-inhibitor0.7055
CYP450 2C9 inhibitorInhibitor0.7067
CYP450 2D6 inhibitorNon-inhibitor0.8442
CYP450 2C19 inhibitorInhibitor0.6281
CYP450 3A4 inhibitorNon-inhibitor0.6542
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8298
Ames testNon AMES toxic0.6842
CarcinogenicityNon-carcinogens0.7004
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4869 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8934
hERG inhibition (predictor II)Non-inhibitor0.5473
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylimidazoles. These are polycyclic aromatic compounds containing a benzene ring linked to an imidazole ring through a CC or CN bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Phenylimidazoles
Alternative Parents
Benzenesulfonamides / Benzenesulfonyl compounds / Phenoxy compounds / Anisoles / Methoxybenzenes / Alkyl aryl ethers / Fluorobenzenes / Organosulfonamides / Aryl chlorides / Aryl fluorides
show 10 more
Substituents
5-phenylimidazole / 1-phenylimidazole / 4-phenylimidazole / Benzenesulfonamide / Benzenesulfonyl group / Anisole / Phenol ether / Phenoxy compound / Methoxybenzene / Halobenzene
show 28 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, aromatic ether, sulfonamide, imidazoles, organochlorine compound (CHEBI:76127)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Almansa C, Bartroli J, Belloc J, Cavalcanti FL, Ferrando R, Gomez LA, Ramis I, Carceller E, Merlos M, Garcia-Rafanell J: New water-soluble sulfonylphosphoramidic acid derivatives of the COX-2 selective inhibitor cimicoxib. A novel approach to sulfonamide prodrugs. J Med Chem. 2004 Oct 21;47(22):5579-82. [PubMed:15481993]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Chegaev K, Lazzarato L, Tosco P, Cena C, Marini E, Rolando B, Carrupt PA, Fruttero R, Gasco A: NO-donor COX-2 inhibitors. New nitrooxy-substituted 1,5-diarylimidazoles endowed with COX-2 inhibitory and vasodilator properties. J Med Chem. 2007 Apr 5;50(7):1449-57. Epub 2007 Mar 3. [PubMed:17335184]

Drug created on October 21, 2007 16:23 / Updated on October 01, 2018 13:59