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
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)
| 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 | ( + / - ) |
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.
Approval Year
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: |
unhealthy, ADULT n = 17 Health Status: unhealthy Condition: psoriasis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 17 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| inconclusive [IC50 25.93 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Inhibition of ornithine decarboxylase and S-adenosylmethionine decarboxylase activities of S49 lymphoma cells by agents increasing cyclic AMP. | 1981 |
|
| Differential modulation of cytokine production by drugs: implications for therapy in heart failure. | 1996 Dec |
|
| Dipyridamole enhances interleukin-1beta-stimulated nitric oxide production by cultured rat vascular smooth muscle cells. | 1996 Feb 5 |
|
| Beta-adrenergic regulation of renin expression in differentiated U-937 monocytic cells. | 1997 Jun 15 |
|
| Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D. | 1997 May 19 |
|
| 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 |
|
| 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 |
|
| Phthalic acid mimics 17beta-estradiol actions in WISH cells. | 2001 Jan 3 |
|
| Role of cyclic nucleotides in vasodilations of the rat thoracic aorta induced by adenosine analogues. | 2001 Jul |
|
| Modulation of excitability in Aplysia tail sensory neurons by tyrosine kinases. | 2001 Jun |
|
| 17beta-estradiol modulates prostaglandin E2 release from human amnion-derived wish cells. | 2001 Jun |
|
| Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse. | 2001 Mar 19 |
|
| [Inhibition of uterine contractions: new in vitro pharmacological approaches on the pregnant human myometrium]. | 2001 May-Jun |
|
| Pharmacological characterization of adenosine receptors in PGT-beta mouse pineal gland tumour cells. | 2001 Sep |
|
| Altered phosphodiesterase 3-mediated cAMP hydrolysis contributes to a hypermotile phenotype in obese JCR:LA-cp rat aortic vascular smooth muscle cells: implications for diabetes-associated cardiovascular disease. | 2002 Apr |
|
| Occupancy of adenosine A2a receptors promotes fMLP-induced cyclic AMP accumulation in human neutrophils: impact on phospholipase D activity and recruitment of small GTPases to membranes. | 2002 Feb |
|
| Nucleotide-evoked relaxation of rat vas deferens: possible mechanisms. | 2002 Feb 1 |
|
| Caffeine eliminates gamma-ray-induced G2-phase delay in human tumor cells but not in normal cells. | 2002 Jan |
|
| Role of cyclic nucleotide phosphodiesterase isoforms in cAMP compartmentation following beta2-adrenergic stimulation of ICa,L in frog ventricular myocytes. | 2003 Aug 15 |
|
| Effects of phosphodiesterase inhibitors on spontaneous nuclear maturation and cAMP concentrations in bovine oocytes. | 2003 Dec |
|
| Group II metabotropic glutamate receptor modulation of excitatory transmission in rat subthalamic nucleus. | 2003 Dec 1 |
|
| The human D2 dopamine receptor synergizes with the A2A adenosine receptor to stimulate adenylyl cyclase in PC12 cells. | 2003 Jul |
|
| Sensitivity of proteasome to its inhibitors increases during cAMP-induced differentiation of neuroblastoma cells in culture and causes decreased viability. | 2004 Feb 10 |
|
| Inhibition of mast cell histamine release by specific phosphodiesterase inhibitors. | 2005 Apr |
|
| Phosphodiesterase IV and neutral endopeptidase in airways from developing and allergen sensitized rabbits. | 2006 |
|
| Chronic ethanol feeding suppresses beta-adrenergic receptor-stimulated lipolysis in adipocytes isolated from epididymal fat. | 2006 Sep |
|
| Numerous distinct PKA-, or EPAC-based, signalling complexes allow selective phosphodiesterase 3 and phosphodiesterase 4 coordination of cell adhesion. | 2007 Dec |
|
| The effect of oxidative stress on macrophages and lung epithelial cells: the role of phosphodiesterases 1 and 4. | 2007 Jan 10 |
|
| Dual regulation of the ATP-sensitive potassium channel by caffeine. | 2007 Jun |
|
| Autoregulation in PC12 cells via P2Y receptors: Evidence for non-exocytotic nucleotide release from neuroendocrine cells. | 2007 Sep |
|
| 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 |
|
| Effect of cyclic AMP on barrier function of human lymphatic microvascular tubes. | 2008 May |
|
| Impact of anti-inflammatory agents on the gene expression profile of stimulated human neutrophils: unraveling endogenous resolution pathways. | 2009 |
|
| Regulation of renovascular adenosine 3',5'-cyclic monophosphate in spontaneously hypertensive rats. | 2009 Aug |
|
| Selective phosphodiesterase inhibitors: a promising target for cognition enhancement. | 2009 Jan |
|
| 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 |
|
| Intravenously administered phosphodiesterase 4 inhibitors dilate retinal blood vessels in rats. | 2009 Jan 5 |
|
| Inhibition of phosphodiesterase has an additive effect on estrogen's ability to inhibit collagen synthesis in vascular smooth muscle cells. | 2009 Jan-Feb |
|
| Endothelin downregulates SERCA2 gene and protein expression in adult rat ventricular myocytes: regulation by pertussis toxin-sensitive Gi protein and cAMP. | 2009 Mar |
|
| Decreased expression and activity of cAMP phosphodiesterases in cardiac hypertrophy and its impact on beta-adrenergic cAMP signals. | 2009 Oct 9 |
|
| Exposure of human seminal vesicle tissue to phosphodiesterase (PDE) inhibitors antagonizes the contraction induced by norepinephrine and increases production of cyclic nucleotides. | 2010 Dec |
|
| Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity. | 2010 Jun |
Sample Use Guides
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
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
Edited
Sat Dec 16 08:45:34 UTC 2023
by
admin
on
Sat Dec 16 08:45:34 UTC 2023
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| Record UNII |
DIW6F13QW2
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| Record Status |
Validated (UNII)
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| Record Version |
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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TARGET -> INHIBITOR |
IC50
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
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