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Identification
NamePiclamilast
Accession NumberDB01791  (EXPT02600)
TypeSmall Molecule
GroupsExperimental
DescriptionPiclamilast (RP-73,401), is a selective PDE4 inhibitor. It is comparable to other PDE4 inhibitors for its anti-inflammatory effects. It has been investigated for its applications to the treatment of conditions such as chronic obstructive pulmonary disease, bronchopulmonary dysplasia and asthma. It is a second generation compound that exhibits structural functionalities of the PDE4 inhibitors cilomilast and roflumilast. The structure for piclamilast was first elucidated in a 1995 European patent application.
Structure
Thumb
Synonyms
RP 73-401
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIWM58D7C3ZT
CAS number144035-83-6
WeightAverage: 381.253
Monoisotopic: 380.069447866
Chemical FormulaC18H18Cl2N2O3
InChI KeyRRRUXBQSQLKHEL-UHFFFAOYSA-N
InChI
InChI=1S/C18H18Cl2N2O3/c1-24-15-7-6-11(8-16(15)25-12-4-2-3-5-12)18(23)22-17-13(19)9-21-10-14(17)20/h6-10,12H,2-5H2,1H3,(H,21,22,23)
IUPAC Name
3-(cyclopentyloxy)-N-(3,5-dichloropyridin-4-yl)-4-methoxybenzamide
SMILES
COC1=CC=C(C=C1OC1CCCC1)C(=O)NC1=C(Cl)C=NC=C1Cl
Pharmacology
IndicationNot Available
Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of action
TargetKindPharmacological actionActionsOrganismUniProt ID
cAMP-specific 3',5'-cyclic phosphodiesterase 4AProteinunknownNot AvailableHumanP27815 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4BProteinunknownNot AvailableHumanQ07343 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4CProteinunknownNot AvailableHumanQ08493 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4DProteinunknownNot AvailableHumanQ08499 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9913
Blood Brain Barrier+0.9833
Caco-2 permeable+0.5977
P-glycoprotein substrateNon-substrate0.6981
P-glycoprotein inhibitor INon-inhibitor0.7
P-glycoprotein inhibitor IINon-inhibitor0.8927
Renal organic cation transporterNon-inhibitor0.7945
CYP450 2C9 substrateNon-substrate0.7619
CYP450 2D6 substrateNon-substrate0.802
CYP450 3A4 substrateSubstrate0.6911
CYP450 1A2 substrateInhibitor0.8545
CYP450 2C9 inhibitorInhibitor0.693
CYP450 2D6 inhibitorNon-inhibitor0.7242
CYP450 2C19 inhibitorInhibitor0.8203
CYP450 3A4 inhibitorInhibitor0.8592
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8983
Ames testNon AMES toxic0.5678
CarcinogenicityNon-carcinogens0.9193
BiodegradationNot ready biodegradable0.9944
Rat acute toxicity2.3047 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9765
hERG inhibition (predictor II)Non-inhibitor0.5623
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0061 mg/mLALOGPS
logP4.65ALOGPS
logP4.09ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)8.25ChemAxon
pKa (Strongest Basic)2.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.45 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity98.38 m3·mol-1ChemAxon
Polarizability37.23 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-arylamides. These are organic compounds that contain a carboxamide group that is N-linked to a aryl group. They have the generic structure RC(=O)N(R')H, R = organyl group and R'= aryl group.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassN-arylamides
Sub ClassNot Available
Direct ParentN-arylamides
Alternative Parents
Substituents
  • N-arylamide
  • Benzoic acid or derivatives
  • Benzamide
  • Methoxybenzene
  • Polyhalopyridine
  • Phenol ether
  • Benzoyl
  • Anisole
  • Aminopyridine
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Molecular Weight:
98142.155 Da
References
  1. Beeh KM, Beier J, Lerch C, Schulz AK, Buhl R: Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable COPD patients. Lung. 2004;182(6):369-77. [PubMed:15765929 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Gene Name:
PDE4B
Uniprot ID:
Q07343
Molecular Weight:
83342.695 Da
References
  1. Beeh KM, Beier J, Lerch C, Schulz AK, Buhl R: Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable COPD patients. Lung. 2004;182(6):369-77. [PubMed:15765929 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4C
Uniprot ID:
Q08493
Molecular Weight:
79900.795 Da
References
  1. Beeh KM, Beier J, Lerch C, Schulz AK, Buhl R: Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable COPD patients. Lung. 2004;182(6):369-77. [PubMed:15765929 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ubiquitin protein ligase binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4D
Uniprot ID:
Q08499
Molecular Weight:
91114.1 Da
References
  1. Beeh KM, Beier J, Lerch C, Schulz AK, Buhl R: Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable COPD patients. Lung. 2004;182(6):369-77. [PubMed:15765929 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23