Piclamilast

Identification

Name
Piclamilast
Accession Number
DB01791  (EXPT02600)
Type
Small Molecule
Groups
Experimental
Description

Piclamilast (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 IDs
RP 73401
Categories
UNII
WM58D7C3ZT
CAS number
144035-83-6
Weight
Average: 381.253
Monoisotopic: 380.069447866
Chemical Formula
C18H18Cl2N2O3
InChI Key
RRRUXBQSQLKHEL-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

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UcAMP-specific 3',5'-cyclic phosphodiesterase 4ANot AvailableHuman
UcAMP-specific 3',5'-cyclic phosphodiesterase 4BNot AvailableHuman
UcAMP-specific 3',5'-cyclic phosphodiesterase 4CNot AvailableHuman
UcAMP-specific 3',5'-cyclic phosphodiesterase 4DNot 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
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
154575
PubChem Substance
46508612
ChemSpider
136184
BindingDB
14775
ChEBI
47619
ChEMBL
CHEMBL42126
HET
PIL
Wikipedia
Piclamilast
PDB Entries
1xm4 / 1xon / 4phl

Clinical Trials

Clinical Trials
Not Available

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 Solubility0.0061 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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Benzamides
Alternative Parents
Polyhalopyridines / Phenoxy compounds / Methoxybenzenes / Benzoyl derivatives / Anisoles / Alkyl aryl ethers / Aryl chlorides / Heteroaromatic compounds / Secondary carboxylic acid amides / Azacyclic compounds
show 5 more
Substituents
Benzamide / Phenoxy compound / Anisole / Benzoyl / Phenol ether / Methoxybenzene / Polyhalopyridine / Alkyl aryl ether / Aryl chloride / Aryl halide
show 18 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, monocarboxylic acid amide, benzamides, chloropyridine (CHEBI:47619)

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
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
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 f...
Gene Name
PDE4B
Uniprot ID
Q07343
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
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
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4C
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
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4D
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]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 13:09