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 8297	0.041 nM [IC50]
Phosphodiesterase 4D 14 Target ID: CHEMBL288 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15576036	Inhibitor 8297	0.021 nM [IC50]
Phosphodiesterase 4A 13 Target ID: CHEMBL254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15339393	Inhibitor 8297
Phosphodiesterase 4 52 Target ID: CHEMBL2093863 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8762090 \| https://www.ncbi.nlm.nih.gov/pubmed/11259554	Inhibitor 8297	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 316 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
The effect of selective phosphodiesterase inhibitors in comparison with other anti-asthma drugs on allergen-induced eosinophilia in guinea-pig airways.	1995 Feb	8535097
Pharmacological modulation of secondary mediator systems--cyclic AMP and cyclic GMP--on inflammatory hyperalgesia.	1999 Jun	10401557
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 Aug	10850854
Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro.	2001 Apr	11259554
Is up-regulation of phosphodiesterase 4 activity by PGE2 involved in the desensitization of beta-mimetics in late pregnancy human myometrium?	2001 Nov	11701706
Anti-TNF-alpha properties of new 9-benzyladenine derivatives with selective phosphodiesterase-4- inhibiting properties.	2001 Oct 26	11606060
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 Apr	11907182
Phosphodiesterase isoenzyme families in human osteoarthritis chondrocytes--functional importance of phosphodiesterase 4.	2002 Feb	11834608
Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors.	2002 Jun	12067300
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
Antidepressant-induced increase in high-affinity rolipram binding sites in rat brain: dependence on noradrenergic and serotonergic function.	2003 Oct	12954819
Pharmacological inhibition of phosphodiesterase 4 triggers ovulation in follicle-stimulating hormone-primed rats.	2005 Jan	15448112
Inhibition of phosphodiesterase activity, airway inflammation and hyperresponsiveness by PDE4 inhibitor and glucocorticoid in a murine model of allergic asthma.	2006 Oct 26	16875702
Inhibition of TGF-beta induced lung fibroblast to myofibroblast conversion by phosphodiesterase inhibiting drugs and activators of soluble guanylyl cyclase.	2007 Oct 15	17659276
Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue.	2008 Mar	18342202
Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice.	2010 May 5	20444277

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 `Fri Dec 15 15:33:42 GMT 2023` Edited by `admin` on `Fri Dec 15 15:33:42 GMT 2023`
Record UNII	WM58D7C3ZT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

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

RP-73401

Code

English

PICLAMILAST [USAN]

Common Name

English

piclamilast [INN]

Common Name

English

RP73401

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C744