101975-10-4 Usage
Description
Zardaverine is a pyridazinone derivative that selectively inhibits phosphodiesterase III (PDE III) from human platelets and phosphodiesterase IV (PDE IV) from human polymorphonuclear leucocytes (PMN). It is a phosphodiesterase inhibitor, with its structure featuring a 4-(difluoromethoxy)-3-methoxyphenyl group substitution at C-6 of the pyridazin-3(2H)-one core. This unique profile makes Zardaverine a promising candidate for various therapeutic applications.
Uses
Used in Pharmaceutical Industry:
Zardaverine is used as a bronchodilator for the treatment of respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Its ability to inhibit PDE III and PDE IV contributes to the relaxation of smooth muscle cells in the airways, leading to improved lung function and reduced symptoms.
Used in Cardiovascular Applications:
Zardaverine is used as a phosphodiesterase III inhibitor for the management of cardiovascular conditions. By inhibiting PDE III, it increases the levels of cyclic AMP (cAMP), which in turn promotes the relaxation of cardiac and vascular smooth muscle cells. This action can help improve heart function and blood flow, providing benefits in the treatment of heart failure and other cardiovascular disorders.
Used in Anti-inflammatory Applications:
Zardaverine's inhibition of PDE IV in human polymorphonuclear leucocytes (PMN) can contribute to its anti-inflammatory properties. By increasing the levels of cAMP, it can modulate the immune response and reduce inflammation, making it a potential candidate for the treatment of inflammatory conditions.
Originator
Zardaverine,ZYF Pharm Chemical
Manufacturing Process
20.8 g of 4-hydroxy-3-methoxyacetophenone are dissolved in 350 ml of
dioxane and 350 ml of water by the addition of 30.0 g of sodium hydroxide,
and the resulting solution is heated to 60°C. While stirring continuously,
chlorodifluoromethane is passed into the solution until uptake of the gas stops
(about 4 h). The solution is cooled, and the resulting precipitate is filtered off
with suction and washed three times with 40 ml of diethyl ether each time.
The solution is diluted with water to twice its volume and likewise extracted
three times with 100 ml of diethyl ether each time. The combined ether
extracts are dried over magnesium sulfate and evaporated in vacuum; the
residue is crystallized from petroleum ether (boiling point 50°-70°C), 19.0 g
(70.4% of theory) of 4-difluoromethoxy-3-methoxyacetophenone are
obtained, melting point 68°C.15.0 g of 4-difluoromethoxy-3-methoxyacetophenone are heated with 5.9 g of
glyoxylic acid monohydrate at 110°C for 2 h. The melt is then cooled to 60°C,
30 ml of water are added, and dissolution is brought about by addition of 10
ml of concentrated aqueous ammonium solution. 3.2 g of hydrazine hydrate
are added, and the mixture is boiled under reflux for 2 h, during which the
title compound gradually crystallizes out. After cooling, the precipitate is
filtered off with suction, thoroughly washed with water, dried and recrystallized from isopropanol. 10.8 g (58.1% of theory) of the 6-(4-
difluoromethoxy-3-methoxyphenyl)-3(2H)pyridazinone are obtained, melting
point 204°C.
Therapeutic Function
Bronchodilator, Anti-asthmatic
Biological Activity
Phosphodiesterase inhibitor, selective for PDE3 and 4 (IC 50 values are 0.5 and 0.8 μ M respectively). Also available as part of the Phosphodiesterase Inhibitor Tocriset? .
Check Digit Verification of cas no
The CAS Registry Mumber 101975-10-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,1,9,7 and 5 respectively; the second part has 2 digits, 1 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 101975-10:
(8*1)+(7*0)+(6*1)+(5*9)+(4*7)+(3*5)+(2*1)+(1*0)=104
104 % 10 = 4
So 101975-10-4 is a valid CAS Registry Number.
InChI:InChI=1/C12H10F2N2O3/c1-18-10-6-7(2-4-9(10)19-12(13)14)8-3-5-11(17)16-15-8/h2-6,12H,1H3,(H,16,17)
101975-10-4Relevant articles and documents
6-(polyfluoroalkoxyphenyl) pyridazinones, their compositions, synthesis and use
-
, (2008/06/13)
6-aryl-3[2H]pyridazinones of formula I STR1 in which one of the substituents R1 and R2 denotes hydrogen or (C1-C4)-alkoxy, and the other denotes polyfluoro-(C1-C4)-alkoxy, and their pharmacologically-tolerated salts are suitable as bronchospasmolytic and cardiotonic active compounds. Processes for their preparation and appropriate medicaments are indicated.
