58-32-2 Usage
Description
Dipyridamole is a phosphodiesterase inhibitor with potent equilibrative nucleoside transporter 1 (ENT1) inhibitory activity and antiplatelet properties.
Used in Pharmaceutical Industry:
Dipyridamole is used as a coronary vasodilating agent for preventing thrombo-formation after cardiac valve replacement in combination with warfarin.
Used in Cardiovascular Applications:
Dipyridamole is used as an antiplatelet agent for preventing platelets from sticking to replacement heart valves and causing blood clots.
Used in Peripheral Arterial Disease Treatment:
Dipyridamole is used as a vasodilator for dilating blood vessels in people with peripheral arterial disease and coronary artery disease.
Used in Research:
Dipyridamole is used as a non-specific nucleoside transport inhibitor to increase the effects of adenosine in sinoatrial and atrioventricular nodes, and as an inhibitor of ENT1 and ENT2.
Used in Drug Development:
Dipyridamole is used as a selective inhibitor of phosphodiesterase V (PDE 5), a potent coronary vasodilator drug, and a cGMP inhibitor for various pharmaceutical applications.
Originator
Persantine,Boehringer Ingelheim,US,1961
Manufacturing Process
Urea may be reacted with acetoacetic ester and that product nitrated to give
5-nitro-orotec acid. That is hydrogenated, then reacted with urea and
potassium cyanate to give tetrahydroxypyrimidopyrimidine. The tetrahydroxy
compound is converted to the tetrachloro compound POCl3. Reaction with
diethanolamine and then with piperidine gives dipyridamole.
Therapeutic Function
Coronary vasodilator
Biological Activity
Coronary vasodilator; adenosine transport inhibitor. Phosphodiesterase inhibitor (IC 50 values are 0.37, 0.38, 0.45, 0.9 and 4.5 μ M? for PDE11, 6, 10, 5 and 8 respectively).
Biochem/physiol Actions
Selective inhibitor of phosphodiesterase V (PDE 5); potent coronary vasodilator drug; adenosine transport inhibitor; inhibitor of platelet aggregation.
Mechanism of action
Dipyridamole exerts its antiplatelet function by increasing cellular concentrations of cAMP
via its inhibition of the degradating enzyme, cyclic nucleotide PDE3. It also blocks adenosine
uptake, which acts at A2 adenosine receptors to stimulate platelet adenyl cyclase. Less common
uses for this drug include inhibition of embolization from prosthetic heart valves when used in
combination with warfarin (the only currently recommended use) and reduction of thrombosis in
patients with thrombotic disease when used in combination with aspirin. Alone, dipyridamole has
little, if any, benefit in the treatment of thrombotic conditions.
Clinical Use
Dipyridamole is a pyrimidopyrimidine derivative with vasodilatory and antiplatelet properties.
Safety Profile
Poison by intraperitoneal and intravenous routes. Moderately toxic by ingestion and subcutaneous routes. Human systemic effects cardiomyopathy including infarction. Mutation data reported. Used as a coronary vasodilator. When heated to decomposition it e
Synthesis
Dipyridamole, 2,2',2'',2'''-[(4,8-dipiperidinopirimido[5,4-d]pirimidin-2,6-
diyl)-diimino]-tetraethanol (19.4.13), is easily synthesized from 5-nitroorotic acid (19.4.8),
easily obtained, in turn, by nitrating of 2,4-dihydroxy-6-methylpyrimidine, which is usually
synthesized by the condensation of urea with acetoacetic ether. Reduction
of the nitro group in 5-nitroorotic acid by various reducing agents gives 5-aminoorotic
acid (19.4.9), which is reacted with urea or with potassium cyanide to give 2,4,6,8-
tetrahydroxypyrimido[5,4-d]pyrimidine (19.4.10). This undergoes a reaction with a mixture
of phosphorous oxychloride and phosphorous pentachloride, which forms 2,4,6,8- tetrachloropyrimido[
5,4-d]pyrimidine (19.4.11). Reacting the resulting tetrachloride with
piperidine replaces the chlorine atoms at C4 and C8 of the heterocyclic system with piperidine,
giving 2,6-dichloropyrimido-4,8-dipiperidino[5,4-d]pyrimidine (19.4.12). Reacting
the resulting product with diethanolamine gives dipyridamole (19.4.13).
Drug interactions
Potentially hazardous interactions with other drugsAnti-arrhythmics: effects of adenosine enhanced and
extended.Anticoagulants: anticoagulant effect of coumarins,
phenindione and heparin enhanced.
Metabolism
Dipyridamole is metabolised in the liver. Renal excretion
of the parent compound is negligible (< 0.5%). Urinary
excretion of the glucuronide metabolite is low (5%), the
metabolites are mostly (about 95%) excreted via the bile
into the faeces, with some evidence of entero-hepatic
recirculation.
References
1) Fujishige et al. (1999), Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A); J. Biol. Chem., 274 18438
2) Soderling et al. (1998), Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase; Proc. Natl. Acad. Sci. USA, 95 8991
3) Lin and Buolamwini (2007), Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.; J. Med. Chem., 50 3906
4) Coccheri (2010), Antiplatelet drugs – do we need new options? With a reappraisal of direct thromboxane inhibitors; Drugs, 70 887
Check Digit Verification of cas no
The CAS Registry Mumber 58-32-2 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 8 respectively; the second part has 2 digits, 3 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 58-32:
(4*5)+(3*8)+(2*3)+(1*2)=52
52 % 10 = 2
So 58-32-2 is a valid CAS Registry Number.
InChI:InChI=1/C24H40N8O4/c1-15(33)31(16(2)34)23-25-19-20(21(27-23)29-11-7-5-8-12-29)26-24(32(17(3)35)18(4)36)28-22(19)30-13-9-6-10-14-30/h15-18,33-36H,5-14H2,1-4H3