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Details

Stereochemistry ACHIRAL
Molecular Formula C20H25NO4
Molecular Weight 343.4168
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CILOMILAST

SMILES

COC1=C(OC2CCCC2)C=C(C=C1)[C@]3(CC[C@@H](CC3)C(O)=O)C#N

InChI

InChIKey=CFBUZOUXXHZCFB-OYOVHJISSA-N
InChI=1S/C20H25NO4/c1-24-17-7-6-15(12-18(17)25-16-4-2-3-5-16)20(13-21)10-8-14(9-11-20)19(22)23/h6-7,12,14,16H,2-5,8-11H2,1H3,(H,22,23)/t14-,20-

HIDE SMILES / InChI

Molecular Formula C20H25NO4
Molecular Weight 343.4168
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description is created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/11772257 and http://www.drugdevelopment-technology.com/projects/ariflo/

Cilomilast (Ariflo) is an oral selective phosphodiesterase (PDE) IV inhibitor under development by GlaxoSmithKline Pharmaceuticals for treatment of COPD. After the demise of Merck's PDE-IV inhibitor (licensed from Celltech Group) in April 2003, Ariflo has emerged as the frontrunner in this new class of agents for inflammatory airways diseases, such as COPD. GlaxoSmithKline filed for drug approval with the US FDA at the end of 2002 and in January 2003 with the European Medicines Evaluation Agency (EMEA). In October 2003 the FDA issued an approvable letter for use of Ariflo in maintenance of lung function in COPD patients poorly responsive to salbutamol, despite an earlier decision by the FDA advisory panel to reject approval. Cilomilast shows high selectivity for cAMP-specific PDE4, an isoenzyme that predominates in pro-inflammatory and immune cells and that is 10-fold more selective for PDE4D than for PDE4A, -B or -C. In vitro, cilomilastsuppresses the activity of several pro-inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD. Moreover, it is highly active in animal models of these diseases. Cilomilast has been shown to exert potent anti-inflammatory effects both in vitro and in vivo.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
96.0 nM [IC50]
12.0 nM [IC50]
115.0 nM [IC50]
86.0 nM [IC50]
308.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ARIFLO

Approved Use

ARIFLO is intended to be used regularly as maintenance therapy for the the treatment of chronic obstructive pulmonary disease (COPD).

Launch Date

2003
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Pharmacological profile of a novel phosphodiesterase 4 inhibitor, 4-(8-benzo[1,2,5]oxadiazol-5-yl-[1,7]naphthyridin-6-yl)-benzoic acid (NVP-ABE171), a 1,7-naphthyridine derivative, with anti-inflammatory activities.
2002 Apr
Update on the therapeutic potential of PDE4 inhibitors.
2002 Jan
Pharmacology of N-(3,5-dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 351591), a novel, orally active phosphodiesterase 4 inhibitor.
2002 Jul
Gateways to clinical trials.
2002 Nov
Gateways to clinical trials.
2002 Oct
Gateways to clinical trials.
2003 Jul-Aug
Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease.
2003 Oct 15
PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease.
2004 Aug
Highly potent PDE4 inhibitors with therapeutic potential.
2004 Jan 5
Gateways to clinical trials.
2004 Jan-Feb
Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors.
2004 Jul 2
Cytokines modulate cilomilast response in lung fibroblasts.
2004 Jun
Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin.
2004 Nov
TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines.
2004 Oct
Lack of pharmacokinetic interactions between cilomilast and theophylline or smoking in healthy volunteers.
2004 Sep
Role of PDE4 in superoxide anion generation through p44/42MAPK regulation: a cAMP and a PKA-independent mechanism.
2004 Sep
Phosphodiesterase-4: selective and dual-specificity inhibitors for the therapy of chronic obstructive pulmonary disease.
2005
Potentiation and prolongation of long-term odor memory in neonate rats using a phosphodiesterase inhibitor.
2005
The effect of selective phosphodiesterase isoenzyme inhibition on neutrophil function in vitro.
2005
The novel phosphodiesterase 4 inhibitor, CI-1044, inhibits LPS-induced TNF-alpha production in whole blood from COPD patients.
2005
Phosphodiesterase 4-selective inhibition: novel therapy for the inflammation of COPD.
2005
CGH2466, a combined adenosine receptor antagonist, p38 mitogen-activated protein kinase and phosphodiesterase type 4 inhibitor with potent in vitro and in vivo anti-inflammatory activities.
2005 Apr
Cilomilast, tacrolimus and rapamycin modulate dendritic cell function in the elicitation phase of allergic contact dermatitis.
2005 Jul
Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene.
2005 Jun
Evidence for a role of phosphodiesterase 4 in lipopolysaccharide-stimulated prostaglandin E2 production and matrix metalloproteinase-9 activity in human amniochorionic membranes.
2005 Jun 15
Selective PDE4 inhibitors as potent anti-inflammatory drugs for the treatment of airway diseases.
2005 Mar
Cilomilast GlaxoSmithKline.
2005 May
The potential role of phosphodiesterase inhibitors in the management of asthma.
2006
Clinical pharmacology of Cilomilast.
2006
Inhibition of airway hyperresponsiveness and pulmonary inflammation by roflumilast and other PDE4 inhibitors.
2006
Effects of cilomilast, a selective phosphodiesterase 4 inhibitor, on esophageal motility and pH, and orocecal and colonic transit: two single-center, randomized, double-blind, placebo-controlled, two-part crossover studies in healthy volunteers.
2006 Apr
Cilomilast.
2006 Apr
[Pharmacological treatment of COPD and future of anti-inflammatory therapy].
2006 Apr 15
An update and appraisal of the cilomilast Phase III clinical development programme for chronic obstructive pulmonary disease.
2006 Aug
The phosphodiesterase type IV inhibitor cilomilast decreases pro-inflammatory cytokine production from primary bronchial epithelial cells in lung transplantation patients.
2006 Dec
Cilomilast for COPD: results of a 6-month, placebo-controlled study of a potent, selective inhibitor of phosphodiesterase 4.
2006 Jan
Involvement of MMP-12 and phosphodiesterase type 4 in cigarette smoke-induced inflammation in mice.
2006 Jun
Phosphodiesterase inhibitors in airways disease.
2006 Mar 8
Roflumilast for the treatment of chronic obstructive pulmonary disease.
2006 May
Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs.
2007
Effects of cyclosporin A and cilomilast on activated canine, murine and human keratinocytes.
2007 Apr
PDE4B5, a novel, super-short, brain-specific cAMP phosphodiesterase-4 variant whose isoform-specifying N-terminal region is identical to that of cAMP phosphodiesterase-4D6 (PDE4D6).
2007 Aug
L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition.
2007 Jun 15
Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis.
2007 Mar
Patents

Sample Use Guides

The recommended dose of ARIFLO is 15 mg twice daily.
Route of Administration: Oral
In Vitro Use Guide
10 uM Cilomilast inhibited the chemotaxis of human fetal lung fibroblasts (HFL-1) toward fibronectin in the blindwell assay system
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:41:28 GMT 2023
Edited
by admin
on Fri Dec 15 15:41:28 GMT 2023
Record UNII
8ATB1C1R6X
Record Status Validated (UNII)
Record Version
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Name Type Language
CILOMILAST
INN   JAN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
cilomilast [INN]
Common Name English
CILOMILAST [MART.]
Common Name English
CILOMILAST [MI]
Common Name English
SB207499
Code English
CILOMILAST [USAN]
Common Name English
CILOMILAST [VANDF]
Common Name English
Cilomilast [WHO-DD]
Common Name English
SB-207499
Code English
CIS-4-CYANO-4-(3-(CYCLOPENTYLOXY)-4-METHOXYPHENYL)CYCLOHEXANECARBOXYLIC ACID
Common Name English
ARIFLO
Brand Name English
CILOMILAST [JAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C744
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
Code System Code Type Description
DRUG BANK
DB03849
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
SMS_ID
100000092735
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
MESH
C433247
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
CAS
153259-65-5
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PRIMARY
INN
7960
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PRIMARY
EPA CompTox
DTXSID6046686
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
FDA UNII
8ATB1C1R6X
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
WIKIPEDIA
CILOMILAST
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
NCI_THESAURUS
C95232
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
EVMPD
SUB01296MIG
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
USAN
JJ-16
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PRIMARY
PUBCHEM
151170
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PRIMARY
ChEMBL
CHEMBL511115
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY
MERCK INDEX
m3549
Created by admin on Fri Dec 15 15:41:28 GMT 2023 , Edited by admin on Fri Dec 15 15:41:28 GMT 2023
PRIMARY Merck Index
Related Record Type Details
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