CAS 101975-10-4|Zardaverine

Introduction：Basic information about CAS 101975-10-4|Zardaverine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Zardaverine BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Articles29
6. Synonyms

Common Name	Zardaverine
CAS Number	101975-10-4	Molecular Weight	268.216
Density	1.4±0.1 g/cm3	Boiling Point	/
Molecular Formula	C₁₂H₁₀F₂N₂O₃	Melting Point	/
MSDS	ChineseUSA	Flash Point	/

Names

Name	zardaverine
Synonym	More Synonyms

Zardaverine BiologicalActivity

Description	Zardaverine is a newly developed dual-selective PDE3/4 inhibitor with IC50 values of 0.5 uM and 0.8 uM respectively. IC50 value: 0.5 uM (PDE3); 0.8 uM (PDE4)Target: PDE3; PDE4Zardaverine inhibited the cyclic GMP-inhibitable PDE III from human platelets and the rolipram-inhibitable PDE IV from canine trachea and human polymorphonuclear (PMN) cells with IC50-values of 0.58, 0.79 and 0.17 μM, respectively. The pyridazinone derivative affected the calmodulin-stimulated PDE I, the cyclic GMP-stimulated PDE II and the cyclic GMP-specific PDE V only marginally at concentrations up to 100μM. Zardaverine inhibits the ADP-induced aggregation of human platelets with an IC50 of 1.6 μM. This inhibition was synergistically increased by activators of adenylate cyclase such as PGE1 and forskolin. In human PMN cells, Zardaverine inhibited the zymosan-induced superoxide anion generation with an IC50 of 0.40 μM. Again, this effect was increased by activators of adenylate cyclase. Zardaverine acted in synergy with the adenylate cyclase activators prostaglandin E2 and CG 4203, a prostacyclin analog, and super-additive effects of combinations were observed. Zardaverine and dexamethasone prevent bronchial eosinophilia and neutrophilia with similar dosage of 30 microM/kg orally, suggesting that this PDE III/IV inhibitor may be useful for both, bronchorelaxation and reduction of inflammation in asthma therapy.
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>Phosphodiesterase (PDE)Research Areas >>Inflammation/Immunology
References	[1]. R.T. Schermuly, H. Leuchte, H.A. Ghofrani, et al. Zardaverine and aerosolised iloprost in a model of acute respiratoryfailure. ERJ, 2003 ,22 (2): 342-347. [2]. D. Ukena, K. Rentz, C. Reiber, et al. Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction. Respiratory Medicine.1995, 89 ( 6) : 441-444. [3]. Schade FU, Schudt C. The specific type III and IV phosphodiesterase inhibitor zardaverine suppresses formation of tumor necrosis factor by macrophages. European Journal of Pharmacology.1993, 230(1):9-14.

Description

Zardaverine is a newly developed dual-selective PDE3/4 inhibitor with IC50 values of 0.5 uM and 0.8 uM respectively. IC50 value: 0.5 uM (PDE3); 0.8 uM (PDE4)Target: PDE3; PDE4Zardaverine inhibited the cyclic GMP-inhibitable PDE III from human platelets and the rolipram-inhibitable PDE IV from canine trachea and human polymorphonuclear (PMN) cells with IC50-values of 0.58, 0.79 and 0.17 μM, respectively. The pyridazinone derivative affected the calmodulin-stimulated PDE I, the cyclic GMP-stimulated PDE II and the cyclic GMP-specific PDE V only marginally at concentrations up to 100μM. Zardaverine inhibits the ADP-induced aggregation of human platelets with an IC50 of 1.6 μM. This inhibition was synergistically increased by activators of adenylate cyclase such as PGE1 and forskolin. In human PMN cells, Zardaverine inhibited the zymosan-induced superoxide anion generation with an IC50 of 0.40 μM. Again, this effect was increased by activators of adenylate cyclase. Zardaverine acted in synergy with the adenylate cyclase activators prostaglandin E2 and CG 4203, a prostacyclin analog, and super-additive effects of combinations were observed. Zardaverine and dexamethasone prevent bronchial eosinophilia and neutrophilia with similar dosage of 30 microM/kg orally, suggesting that this PDE III/IV inhibitor may be useful for both, bronchorelaxation and reduction of inflammation in asthma therapy.

Related Catalog

Signaling Pathways >>Metabolic Enzyme/Protease >>Phosphodiesterase (PDE)Research Areas >>Inflammation/Immunology

References

[1]. R.T. Schermuly, H. Leuchte, H.A. Ghofrani, et al. Zardaverine and aerosolised iloprost in a model of acute respiratoryfailure. ERJ, 2003 ,22 (2): 342-347.

[2]. D. Ukena, K. Rentz, C. Reiber, et al. Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction. Respiratory Medicine.1995, 89 ( 6) : 441-444.

[3]. Schade FU, Schudt C. The specific type III and IV phosphodiesterase inhibitor zardaverine suppresses formation of tumor necrosis factor by macrophages. European Journal of Pharmacology.1993, 230(1):9-14.

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Molecular Formula	C₁₂H₁₀F₂N₂O₃
Molecular Weight	268.216
Exact Mass	268.065948
PSA	64.21000
LogP	0.90
Index of Refraction	1.555
InChIKey	HJMQDJPMQIHLPB-UHFFFAOYSA-N
SMILES	COc1cc(-c2ccc(=O)[nH]n2)ccc1OC(F)F
Storage condition	2-8℃

Safety Information

Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
RIDADR	NONH for all modes of transport

Articles29

Uncovering caffeine's adenosine A2A receptor inverse agonism in experimental parkinsonism.

ACS Chem. Biol. 9(11) , 2496-501, (2014)

Caffeine, the most consumed psychoactive substance worldwide, may have beneficial effects on Parkinson's disease (PD) therapy. The mechanism by which caffeine contributes to its antiparkinsonian effec...

Dopamine receptors D3 and D5 regulate CD4(+)T-cell activation and differentiation by modulating ERK activation and cAMP production.

J. Neuroimmunol. 284 , 18-29, (2015)

Dopamine receptors have been described in T-cells, however their signalling pathways coupled remain unknown. Since cAMP and ERKs play key roles regulating T-cell physiology, we aim to determine whethe...

Phenotype-based screening of mechanistically annotated compounds in combination with gene expression and pathway analysis identifies candidate drug targets in a human squamous carcinoma cell model.

J. Biomol. Screen. 11(5) , 457-68, (2006)

The squamous cell carcinoma HeLa cell line and an epithelial cell line hTERT-RPE with a nonmalignant phenotype were interrogated for HeLa cell selectivity in response to 1267 annotated compounds repre...

Synonyms

3-[4-(difluoromethoxy)-3-methoxyphenyl]-1H-pyridazin-6-one

3-pyridazinol, 6-[4-(difluoromethoxy)-3-methoxyphenyl]-

Zardaverine

3(2H)-Pyridazinone, 6-[4-(difluoromethoxy)-3-methoxyphenyl]-

6-[4-(Difluoromethoxy)-3-methoxyphenyl]-3(2H)-pyridazinone

zardaverinum

zardaverina

6-[4-(Difluoromethoxy)-3-methoxyphenyl]pyridazin-3(2H)-one

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