| Identification | Back Directory | [Name]
Dypyridamole | [CAS]
58-32-2 | [Synonyms]
ra8
RA 8
Natyl
Piroan
Anginal
Apricor
Coribon
Coridil
Corosan
Coroxin
Curantyl
Agilease
Cardoxil
Prandiol
Kurantil
Protangix
usafge-12
persantin
Peridamol
Permiltin
Dipyridan
Chilcolan
Cleridium
Coronarine
Cardioflux
Gulliostin
Persantine
NSC-515776
Justpertin
USAF Ge-12
dipridacot
DIPYRIDAMOL
Stenocardil
Dypyridamol
Dipyrdamole
etraethanol
Prandiol 75
Dipyudamine
Dipiridamol
Dipyridamine
cleridium150
Stenocardiol
Stimolcardio
DIPYRIDAMOLE
DIPYRIDAZOLE
dypyridamole
itrilo)tetra-
Cleridium 150
Dipyridamole,98%
DIPYRIDAMOLE,USP
DypyridaMole API
Dipyridamole (FDA)
Dipyridamole (200 mg)
DIPYRIDAMOLE CORONARY VASODILATOR
2,6-BIS(DIETHANOLAMINE)-4,8-DIPIPERIDINOPYRIMIDO[5,4-D]PYRIMIDINE
2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]pyrimidin
2,6-BIS(DIETHANOLAMINO)-4,8-DIPIPERIDINOPYRIMIDO[5,4-D]PYRIMIDINE
Pyrimido(5,4-d)pyrimidine, 2,6-bis(bis(2-hydroxyethyl)amino)-4,8-diperidino-
pyrimido(5,4-d)pyrimidine,2,6-bis(bis(2-hydroxyethyl)amino)-4,8-dipiperidino
2,2’,2’’,2’’’-(4,8-dipiperidinopyrimido(5,4-d)pyrimidine-2,6-diyldinitrilo)t
ethanol,2,2’,2’’,2’’’-((4,8-dipiperidinopyrimido(5,4-d)pyrimidine-2,6-diyl)din
Pyrimido(5,4-d)pyrimidine, 2,6-bis(bis(2-hydroxyethyl)amino)-4,8-dipiperidino-
2,2',2'',2'''-4,8-DIPIPERIDINO-PYRIMIDO [5,4-D] PYRIMIDINE-2,6-DIYLDINITRILOTETRAETHANOL
Ethanol, 2,2',2'',2'''-(4,8-dipiperidinopyrimido(5,4-d)pyrimidine-2,6-diyldinitrilo)tetra-
2,2',2'',2'''-[(4,8-Dipiperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetraethanol
2,2',2'',2'''-[(4,8-DIPIPERIDINYLPYRIMIDO[5,4-D]PYRIMIDINE-2,6-DIYL)DINITRILO]TETRAKISETHANOL
2,2’,2’’,2’’’-[(4,8-Di-1-piperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetrakisethanol
2,2',2'',2'''-((4,8-Di(piperidin-1-yl)pyrimido[5,4-d]-pyrimidine-2,6-diyl)bis(azanetriyl))tetraet
Ethanol, 2,2',2'',2'''-[(4,8-di-1-piperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetrakis-
2,2',2'',2'''-((4,8-Di(piperidin-1-yl)pyriMido[5,4-d]pyriMidine-2,6-diyl)bis(azanetriyl))tetraethanol
2-[[2-[bis(2-hydroxyethyl)amino]-4,8-dipiperidino-pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol
2-[[2-[bis(2-hydroxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol
2,6-Bis(diethanolamine)-4,8-dipiperidinopyrimido[5,4-d]pyrimidine
2,2',2'',2'''-[(4,8-Dipiperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetrakisethanol | [EINECS(EC#)]
200-374-7 | [Molecular Formula]
C24H40N8O4 | [MDL Number]
MFCD00010555 | [MOL File]
58-32-2.mol | [Molecular Weight]
504.63 |
| Chemical Properties | Back Directory | [Appearance]
Yellow Powder | [Melting point ]
165-166 °C (lit.) | [Boiling point ]
593.96°C (rough estimate) | [density ]
1.2046 (rough estimate) | [refractive index ]
1.6910 (estimate) | [storage temp. ]
−20°C
| [solubility ]
DMSO: soluble
| [form ]
powder
| [pka]
pKa 6.4 (Uncertain) | [color ]
yellow
| [Water Solubility ]
Soluble in chloroform, methanol, dilute acids, ethanol. Slightly soluble in water. | [Merck ]
3346 | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. | [NIST Chemistry Reference]
Pyrimidine, 2,6-bis(diethanolamino)-4,8-dipiperidino-pyrimido-(5,4-d)-(58-32-2) |
| Hazard Information | Back Directory | [Chemical Properties]
Yellow Powder | [Usage]
A phosphodiester, cGMP, and non-specific nucleoside transport inhibitor | [Usage]
Selective inhibitor of phosphodiesterase V (PDE 5); potent coronary vasodilator drug; adenosine transport inhibitor; inhibitor of platelet aggregation | [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). | [Description]
Dipyridamole (58-32-2) is a phosphodiesterase inhibitor (IC50=0.37, 0.38, 0.45, 0.9 and 4.5 μM for PDE11, 6, 10, 5 and 8 respectively.1,2 Potent equilibrative nucleoside transporter 1 (ENT1) inhibitor Ki=8.2 nM vs. 144.8 nM for ENT1 and ENT2 respectively.3 Antiplatelet activity.4 | [Originator]
Persantine,Boehringer Ingelheim,US,1961 | [Uses]
A phosphodiester, cGMP, and non-specific nucleoside transport inhibitor | [Uses]
Dipiridamol is known as a coronary vasodilating agent, although it also possesses specific
antiaggregant activity. It is used for preventing thrombo-formation after cardiac valve
replacement in combination with warfarin. | [Uses]
Selective inhibitor of phosphodiesterase V (PDE 5); potent coronary vasodilator drug; adenosine transport inhibitor; inhibitor of platelet aggregation | [Definition]
ChEBI: A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots. | [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. | [Brand name]
Persantine (Boehringer Ingelheim). | [Therapeutic Function]
Coronary vasodilator | [General Description]
Dipyridamole, 2,2',2',2'''-[(4,8-di-1piperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]-tetrakisethanol (Persantine), may be used for coronary andmyocardial insufficiency. Its biggest use today, however, isas an antithrombotic in patients with prosthetic heart valves.It is a bitter, yellow, crystalline powder, soluble in diluteacids, methanol, or chloroform. A formulation containingdipyridamole and aspirin (Aggrenox) is currently beingmarketed as an antithromobotic.
Dipyridamole is a long-acting vasodilator. Its vasodilatingaction is selective for the coronary system; it is indicatedfor long-term therapy of chronic angina pectoris. Thedrug also inhibits adenosine deaminase in erythrocytesand interferes with the uptake of the vasodilator adenosineby erythrocytes. These actions potentiate the effect ofprostacyclin (PGI2), which acts as an inhibitor to plateletaggregation. | [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 drugs
Anti-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. | [storage]
Store at RT | [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 |
| Safety Data | Back Directory | [Hazard Codes ]
Xi | [Risk Statements ]
36/37/38 | [Safety Statements ]
26-36 | [WGK Germany ]
2
| [RTECS ]
KK7450000
| [HS Code ]
29335990 | [Toxicity]
LD50 in rats: 8.4 g/kg orally; 208 mg/kg i.v. (Takenaka) |
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