PICLAMILAST

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H18Cl2N2O3
Molecular Weight	381.253
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(OC2CCCC2)C=C(C=C1)C(=O)NC3=C(Cl)C=NC=C3Cl

InChI

InChIKey=RRRUXBQSQLKHEL-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C18H18Cl2N2O3
Molecular Weight	381.253
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://newdrugapprovals.org/2014/03/19/piclamilast/
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800004110 http://www.drugbank.ca/drugs/DB01791 https://www.ncbi.nlm.nih.gov/pubmed/7613200 https://www.ncbi.nlm.nih.gov/pubmed/9316851

Piclamilast (RP 73401), 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 asthma, dermatitis, rheumatoid arthritis. Emesis is the most commonly cited side effect of piclamilast.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphodiesterase 4B 11 Target ID: CHEMBL275 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15576036	Inhibitor 8504	0.041 nM [IC50]
Phosphodiesterase 4D 14 Target ID: CHEMBL288 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15576036	Inhibitor 8504	0.021 nM [IC50]
Phosphodiesterase 4A 13 Target ID: CHEMBL254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15339393	Inhibitor 8504
Phosphodiesterase 4 54 Target ID: CHEMBL2093863 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8762090 \| https://www.ncbi.nlm.nih.gov/pubmed/11259554	Inhibitor 8504	0.0012 µM [IC50]
Cytochrome P450 2B6 19 Target ID: CHEMBL4729 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9316851	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Allergic asthma 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16875702	Primary	Preclinical	Unknown Approved Use Unknown
Immunological dermatitis 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10748277 http://adisinsight.springer.com/drugs/800004110	Primary	Preclinical	Unknown Approved Use Unknown
Rheumatoid arthritis 320 Sources: http://adisinsight.springer.com/drugs/800004110 https://www.ncbi.nlm.nih.gov/pubmed/14998551	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Pharmacological validation of Trypanosoma brucei phosphodiesterases B1 and B2 as druggable targets for African sleeping sickness.	2011-12-08	22023548
PDE8 regulates rapid Teff cell adhesion and proliferation independent of ICER.	2010-08-09	20711499
Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice.	2010-05-05	20444277
Cytokine-dependent balance of mitogenic effects in primary human lung fibroblasts related to cyclic AMP signaling and phosphodiesterase 4 inhibition.	2010-05	20082309
Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury.	2009-04-29	19402887
Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking?	2008-10	18660832
Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue.	2008-03	18342202
Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung injury.	2008-03	18094015
ABCD of the phosphodiesterase family: interaction and differential activity in COPD.	2008	19281073
Effects of phosphodiesterase 4 inhibition on alveolarization and hyperoxia toxicity in newborn rats.	2008	18941502
Correlation between emetic effect of phosphodiesterase 4 inhibitors and their occupation of the high-affinity rolipram binding site in Suncus murinus brain.	2007-11-14	17658510
Inhibition of TGF-beta induced lung fibroblast to myofibroblast conversion by phosphodiesterase inhibiting drugs and activators of soluble guanylyl cyclase.	2007-10-15	17659276
Treating COPD with PDE 4 inhibitors.	2007	18268925
Inhibition of phosphodiesterase activity, airway inflammation and hyperresponsiveness by PDE4 inhibitor and glucocorticoid in a murine model of allergic asthma.	2006-10-26	16875702
Effects of ciclamilast, a new PDE 4 PDE4 inhibitor, on airway hyperresponsiveness, PDE4D expression and airway inflammation in a murine model of asthma.	2006-10-10	16956605
Phosphodiesterase type 4 inhibitors cause proinflammatory effects in vivo.	2006-10	16861399
Antidepressant-like effects of PDE4 inhibitors mediated by the high-affinity rolipram binding state (HARBS) of the phosphodiesterase-4 enzyme (PDE4) in rats.	2006-06	16586089
Inhibition of airway hyperresponsiveness and pulmonary inflammation by roflumilast and other PDE4 inhibitors.	2006	16257550
Pharmacological inhibition of phosphodiesterase 4 triggers ovulation in follicle-stimulating hormone-primed rats.	2005-01	15448112
Phosphodiesterase IV inhibition by piclamilast potentiates the cytodifferentiating action of retinoids in myeloid leukemia cells. Cross-talk between the cAMP and the retinoic acid signaling pathways.	2004-10-01	15292163
Selective inhibition of purified human phosphodiesterase 4A expressed in yeast cell GL62 by ciclamilast, piclamilast, and rolipram.	2004-09	15339393
Differential effect of phosphodiesterase IV inhibitor RP73401 on various inflammatory and immune responses relevent to rheumatoid arthritis.	2004-05	14998551
[Phosphosdiesterase 4 inhibitors in the treatment of pulmonary diseases].	2004-01	14989829
Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable COPD patients.	2004	15765929
Antidepressant-induced increase in high-affinity rolipram binding sites in rat brain: dependence on noradrenergic and serotonergic function.	2003-10	12954819
[Comparison of piclamilast with ciclamilast in bronchodilating and antiallergic effects].	2003-08	14521139
Inhibitor binding to type 4 phosphodiesterase (PDE4) assessed using [3H]piclamilast and [3H]rolipram.	2003-05	12704225
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003-01-01	12464242
Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors.	2002-06	12067300
The selective phosphodiesterase 4 inhibitor RP 73-401 reduced matrix metalloproteinase 9 activity and transforming growth factor-beta release during acute lung injury in mice: the role of the balance between Tumor necrosis factor-alpha and interleukin-10.	2002-04	11907182
Phosphodiesterase isoenzyme families in human osteoarthritis chondrocytes--functional importance of phosphodiesterase 4.	2002-02	11834608
Is up-regulation of phosphodiesterase 4 activity by PGE2 involved in the desensitization of beta-mimetics in late pregnancy human myometrium?	2001-11	11701706
Anti-TNF-alpha properties of new 9-benzyladenine derivatives with selective phosphodiesterase-4- inhibiting properties.	2001-10-26	11606060
Modulation of eotaxin formation and eosinophil migration by selective inhibitors of phosphodiesterase type 4 isoenzyme.	2001-09	11564646
[Inhibition of uterine contractions: new in vitro pharmacological approaches on the pregnant human myometrium].	2001-07-31	11475797
Effects of PDE4 inhibitors on lipopolysaccharide-induced priming of superoxide anion production from human mononuclear cells.	2001-06	11545248
Requirement of additional adenylate cyclase activation for the inhibition of human eosinophil degranulation by phosphodiesterase IV inhibitors.	2001-04-06	11301054
Role of p38 MAP kinase in LPS-induced airway inflammation in the rat.	2001-04	11309243
In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor.	2001-04	11259555
Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro.	2001-04	11259554
Identification of substrate specificity determinants in human cAMP-specific phosphodiesterase 4A by single-point mutagenesis.	2001-03	11282454
Phthalazine PDE4 inhibitors. Part 2: the synthesis and biological evaluation of 6-methoxy-1,4-disubstituted derivatives.	2001-01-08	11140727
Effects of several glucocorticosteroids and PDE4 inhibitors on increases in total lung eosinophil peroxidase (EPO) levels following either systemic or intratracheal administration in sephadex- or ovalbumin-induced inflammatory models.	2000-08	10850854
Pharmacological modulation of secondary mediator systems--cyclic AMP and cyclic GMP--on inflammatory hyperalgesia.	1999-06	10401557
The effect of selective phosphodiesterase inhibitors in comparison with other anti-asthma drugs on allergen-induced eosinophilia in guinea-pig airways.	1995-02	8535097

Patents

Sample Use Guides

In Vivo Use Guide

1, 3 and 10 mg/kg were orally administered once daily

Route of Administration: Oral

In Vitro Use Guide

RP 73401 (IC50: 6.9 +/- 3.3 nM, n = 5) was 71 fold more potent than (+/-)-rolipram (IC50: 490 +/- 260 nM, n = 4) in inhibiting LPS-induced TNF alpha release from monocytes. RP 73401 (IC50: 2 nM) was 180 fold more potent than rolipram (IC50: 360 nM) in suppressing LPS (10 ng ml-1)-induced TNF alpha mRNA.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:01:13 GMT 2025` Edited by `admin` on `Mon Mar 31 18:01:13 GMT 2025`
Record UNII	WM58D7C3ZT
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

RP-73401

Preferred Name

English

PICLAMILAST

Official Name

English

BENZAMIDE, 3-(CYCLOPENTYLOXY)-N-(3,5-DICHLORO-4-PYRIDINYL)-4-METHOXY-

Systematic Name

English

RPR-73401

Code

English

3-(CYCLOPENTYLOXY)-N-(3,5-DICHLORO-4-PYRIDYL)-P-ANISAMIDE

Common Name

English

Piclamilast [WHO-DD]

Common Name

English

PICLAMILAST [USAN]

Common Name

English

piclamilast [INN]

Common Name

English

RP73401

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C744