RO-20-1724

Details

Stereochemistry	RACEMIC
Molecular Formula	C15H22N2O3
Molecular Weight	278.3468
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCOC1=CC(CC2CNC(=O)N2)=CC=C1OC

InChI

InChIKey=PDMUULPVBYQBBK-UHFFFAOYSA-N

InChI=1S/C15H22N2O3/c1-3-4-7-20-14-9-11(5-6-13(14)19-2)8-12-10-16-15(18)17-12/h5-6,9,12H,3-4,7-8,10H2,1-2H3,(H2,16,17,18)

HIDE SMILES / InChI

Molecular Formula	C15H22N2O3
Molecular Weight	278.3468
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/383851 | https://www.ncbi.nlm.nih.gov/pubmed/7521256 | https://www.ncbi.nlm.nih.gov/pubmed/4348178 | https://www.ncbi.nlm.nih.gov/pubmed/10900250 | https://www.ncbi.nlm.nih.gov/pubmed/10704053

RO-20-1724 is a potent inhibitor of Phosphodiesterase 4 (PDE4) originally developed by Roche. It showed some promise as a potential treatment for psoriasis, but it was discontinued when it could not match the efficacy of existing treatments. RO-20-1724 was also investigated as a potential treatment for asthma and septic shock.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 4 52 Target ID: CHEMBL2093863 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1393276	Inhibitor 8297		4.73 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Asthma 241 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10704053 https://www.ncbi.nlm.nih.gov/pubmed/10900250	Primary	Preclinical	Unknown Approved Use Unknown
Psoriasis 84 Sources: https://www.ncbi.nlm.nih.gov/pubmed/383851	Primary	Phase II 1132	Unknown Approved Use Unknown
Septic shock 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7521256 https://www.ncbi.nlm.nih.gov/pubmed/12235272	Primary	Preclinical	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
1 % 4 times / day multiple, topical (unknown) Studied dose Dose: 1 %, 4 times / day Route: topical Route: multiple Dose: 1 %, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/383851	unhealthy, ADULT n = 17 Health Status: unhealthy Condition: psoriasis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/383851	Sources: https://pubmed.ncbi.nlm.nih.gov/383851

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 UMAT 3 CYP1A2 1524 CYP2A6 707 CYP2E1 882 P-gp 1461

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1347076#sid=46500386	inconclusive [IC50 25.93 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625245#sid=103183095	no [IC50 >10 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625246#sid=103183095	no [IC50 >10 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625247#sid=103183095	no [IC50 >10 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625248#sid=103183095	no [IC50 >10 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625249#sid=103183095	no [IC50 >10 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625250#sid=103183095	no [IC50 >10 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625251#sid=103183095	no [IC50 >10 uM]
UMAT 3	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/602162#sid=46500386	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=50104396

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY547107	https://www.001chemical.com/chem/29925-17-5
3B Scientific (Wuhan) Corp	3B3-053716	http://www.3bsc.com/index/pro_info.php?id=92181
AA Blocks	AA01E3ZT	https://www.aablocks.com/goods/Goods/detail?id=AA01E3ZT
AHH Chemical co.,ltd	MT-39726	http://www.ahhchemical.com/product/MT-39726.html
Alfa Chemistry	AP29925175-A	https://reagents.alfa-chemistry.com/product/4-3-butoxy-4-methoxybenzyl-imidazolidin-cas-29925-17-5-9450.html
Alfa Chemistry	AP29925175-B	https://reagents.alfa-chemistry.com/product/ro-20-1724-cas-29925-17-5-cas-29925-17-5-9451.html
Alfa Chemistry	29925-17-5	https://www.alfa-chemistry.com/cas_29925-17-5.htm
Aurora Fine Chemicals LLC	A17.880.044	http://online.aurorafinechemicals.com/info?ID=A17.880.044
AvaChem Scientific	6741	https://www.avachem.com/productSearch.asp?6741
BLD Pharm	BD150473	http://www.bldpharm.com/products/29925-17-5.html
BOC Sciences	29925-17-5	https://www.bocsci.com/ro-20-1724-cas-29925-17-5-item-62964.html
BioCrick	BCC6638	http://www.biocrick.com/Ro-20-1724-BCC6638.html
BioSynth	J-017698	https://www.biosynth.com/en/products/all-products/products/J-017698.html
CSNpharm	CSN23068	https://www.csnpharm.com/products/ro-20-1724.html
Calbiochem	557502	http://www.emdbiosciences.com/product/557502
ChemMol	97900414	http://www.chemmol.com/chemmol/97900414.html
Chemspace	CSSB00000133408	https://chem-space.com/CSSB00000133408
EMD Millipore	557502	http://www.emdbiosciences.com/product/557502
Finetech	FT-0712648	http://www.finetechnology-ind.com/prod/detail/pub/29925-17-5.html
Glentham Life Sciences	GL0430	http://www.glentham.com/products/product/GL0430/
MolPort	MolPort-003-666-578	https://www.molport.com/shop/molecule-link/MolPort-003-666-578
Molcore	MC547107	https://www.molcore.com/product/29925-17-5
MuseChem	I009102	https://www.musechem.com/product/I009102.html
Oakwood	M02450	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=127256&ExtHyperLink=1
Sigma-Aldrich	B8279_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/b8279?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S541599	http://www.smolecule.com/products/s541599
THE BioTek	bt-281534	https://www.thebiotek.com/product/inhibitors/bt-281534
TimTec	ST044509	http://www.echemstore.com/st044509-4-3-butoxy-4-methoxyphenyl-methyl-imidazolidin-2-one.html
Tocris	415	https://www.tocris.com/products/ro-20-1724_0415
eNovation Chemicals	D668521	https://www.enovationchem.com/ProductDetails.asp?ProductID=D668521
mcule	MCULE-9512543923	https://mcule.com/MCULE-9512543923/

PubMed

Title	Date	PubMed
Dipyridamole enhances interleukin-1beta-stimulated nitric oxide production by cultured rat vascular smooth muscle cells.	1996 Feb 5	8904084
Beta-adrenergic regulation of renin expression in differentiated U-937 monocytic cells.	1997 Jun 15	9256163
Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D.	1997 May 19	9177268
Phosphodiesterase type 4 inhibitors, but not glucocorticoids, are more potent in suppression of cytokine secretion by mononuclear cells from atopic than nonatopic donors.	1998 Nov	9819297
Chronic type IV phosphodiesterase inhibition protects glomerular filtration rate and renal and mesenteric blood flow in a zymosan-induced model of multiple organ dysfunction syndrome treated with norepinephrine.	2001 Jan	11123377
Phthalic acid mimics 17beta-estradiol actions in WISH cells.	2001 Jan 3	11137322
Role of cyclic nucleotides in vasodilations of the rat thoracic aorta induced by adenosine analogues.	2001 Jul	11454656
Caffeine eliminates gamma-ray-induced G2-phase delay in human tumor cells but not in normal cells.	2002 Jan	11754638
The human D2 dopamine receptor synergizes with the A2A adenosine receptor to stimulate adenylyl cyclase in PC12 cells.	2003 Jul	12784121
Phosphodiesterase type IV inhibitors prevent ischemia-reperfusion-induced gastric injury in rats.	2004 Jul	15272207
Phosphodiesterase-linked inhibition of nonmicturition activity in the isolated bladder.	2004 Jun	15180632
The effect of selective phosphodiesterase inhibitors, alone and in combination, on a murine model of allergic asthma.	2004 May 5	15169552
Inhibition of mast cell histamine release by specific phosphodiesterase inhibitors.	2005 Apr	15928811
Characteristics of taurine release in slices from adult and developing mouse brain stem.	2006 Jul	16680399
Ca(2+)-dependent K(+) currents and spike-frequency adaptation in medial entorhinal cortex layer II stellate cells.	2007	17880008
Numerous distinct PKA-, or EPAC-based, signalling complexes allow selective phosphodiesterase 3 and phosphodiesterase 4 coordination of cell adhesion.	2007 Dec	17884339
Differential regulation of synaptic transmission by adrenergic agonists via protein kinase A and protein kinase C in layer V pyramidal neurons of rat cerebral cortex.	2007 Jun 8	17478051
Autoregulation in PC12 cells via P2Y receptors: Evidence for non-exocytotic nucleotide release from neuroendocrine cells.	2007 Sep	18404450
Antipsychotic-like properties of phosphodiesterase 4 inhibitors: evaluation of 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO-20-1724) with auditory event-related potentials and prepulse inhibition of startle.	2008 Jul	18420599
Effect of cyclic AMP on barrier function of human lymphatic microvascular tubes.	2008 May	18440562
Selective phosphodiesterase inhibitors: a promising target for cognition enhancement.	2009 Jan	18709359
Adrenomedullin-induced relaxation of rat brain pericytes is related to the reduced phosphorylation of myosin light chain through the cAMP/PKA signaling pathway.	2009 Jan 2	18983892
Inhibition of phosphodiesterase has an additive effect on estrogen's ability to inhibit collagen synthesis in vascular smooth muscle cells.	2009 Jan-Feb	19007913
Exposure of human seminal vesicle tissue to phosphodiesterase (PDE) inhibitors antagonizes the contraction induced by norepinephrine and increases production of cyclic nucleotides.	2010 Dec	20970829

Patents

Sample Use Guides

In Vivo Use Guide

In a clinical trial for the treatment of psoriasis, a 1% RO-20-1724 cream was applied 4 times a day for 4 weeks to affected areas. RO-20-1724 was not as effective as intensive occlusive treatment of psoriatic lesions with 0.025% triamcinolone acetonide

Route of Administration: Topical

In Vitro Use Guide

Aortic vascular smooth muscle (VSM) cells were harvested from enzymatically dissociated rat thoracic aorta. Cells were stimulated by incubation with interleukin-lp (IL-10) at different concentrations for varying periods of time up to 48 h, with and without RO-20-1724. Nitric Oxide Synthase activity was assessed by measurement of nitrite production. RO-20-1724 had no detectable effect on nitrite levels in the absence of IL-lp but enhanced the production of nitrite in response to IL-Il in a dose-dependent manner.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:45:34 GMT 2023` Edited by `admin` on `Sat Dec 16 08:45:34 GMT 2023`
Record UNII	DIW6F13QW2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RO-20-1724

Common Name

English

ROCHE 20-1724

Code

English

4-(3-BUTOXY-4-METHOXYBENZYL)-2-IMIDAZOLIDINONE

Systematic Name

English

DL-4-(3-BUTOXY-4-METHOXYBENZYL)-2-IMIDAZOLIDINONE

Systematic Name

English

2-IMIDAZOLIDINONE, 4-((3-BUTOXY-4-METHOXYPHENYL)METHYL)-

Systematic Name

English

RO-20-174

Code

English

Code System Code Type Description

CAS

29925-17-5

Created by admin on Sat Dec 16 08:45:34 GMT 2023 , Edited by admin on Sat Dec 16 08:45:34 GMT 2023

PRIMARY

FDA UNII

DIW6F13QW2

Created by admin on Sat Dec 16 08:45:34 GMT 2023 , Edited by admin on Sat Dec 16 08:45:34 GMT 2023

PRIMARY

EPA CompTox

DTXSID80952376

Created by admin on Sat Dec 16 08:45:34 GMT 2023 , Edited by admin on Sat Dec 16 08:45:34 GMT 2023

PRIMARY

PUBCHEM

5087

Created by admin on Sat Dec 16 08:45:34 GMT 2023 , Edited by admin on Sat Dec 16 08:45:34 GMT 2023

PRIMARY

Related Record Type Details


					FMS08T2916

CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE 4D

TARGET -> INHIBITOR

Qualification:

IC50

Amount:

Related Record Type Details


					DIW6F13QW2

RO-20-1724

ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/383851 | https://www.ncbi.nlm.nih.gov/pubmed/7521256 | https://www.ncbi.nlm.nih.gov/pubmed/4348178 | https://www.ncbi.nlm.nih.gov/pubmed/10900250 | https://www.ncbi.nlm.nih.gov/pubmed/10704053

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Doses

Overview

OverviewOther

Drug as perpetrator​

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/383851 | https://www.ncbi.nlm.nih.gov/pubmed/7521256 | https://www.ncbi.nlm.nih.gov/pubmed/4348178 | https://www.ncbi.nlm.nih.gov/pubmed/10900250 | https://www.ncbi.nlm.nih.gov/pubmed/10704053

Drug as perpetrator