| Identification | More | [Name]
Amiloride hydrochloride | [CAS]
2016-88-8 | [Synonyms]
3,5-DIAMINO-6-CHLORO-N-(DIAMINOMETHYLIDENE)PYRAZINE-2-CARBOXAMIDE
3,5-DIAMINO-N-(AMINOIMINOMETHYL)-6-CHLOROPYRAZINECARBOXAMIDE HYDROCHLORIDE
3,5-DIAMINO-N-(AMINOMETHYL)-6-CHLOROPYRAZINE CARBOXAMIDE HYDROCHLORIDE
AMILORIDE HCL
AMILORIDE HCL HYDRATE
AMILORIDE HYDROCHLORIDE
AMILORIDE HYDROCHLORIDE HYDRATE
AMIPRAMIDIN
AMIPRAMIZIDE
GUANAMPRAZINE
N-AMIDINO-3,5-DIAMINO-6-CHLOROPYRAZINECARBOXAMIDE HYDROCHLORIDE
amiloridechloride
amiprazidine
n-amidino-3,5-diamino-6-chloro-pyrazinecarboxamidmonohydrochloride
N-amidino-3,5-diamino-6-chloropyrazinecarboxamide monohydrochloride
HCL AMILORIDE HCL
Amipramidin hydrochloride
Amipramizide hydrochloride
Guanamprazine hydrochloride
Pyrazinecarboxamide, 3,5-diamino-N-(aminoiminomethyl)-6-chloro-, monohydrochloride | [EINECS(EC#)]
217-958-2 | [Molecular Formula]
C6H11Cl2N7O2 | [MDL Number]
MFCD03703482 | [Molecular Weight]
284.1 | [MOL File]
2016-88-8.mol |
| Safety Data | Back Directory | [Hazard Codes ]
T,Xi | [Risk Statements ]
R25:Toxic if swallowed.
R36/37/38:Irritating to eyes, respiratory system and skin . | [Safety Statements ]
S36:Wear suitable protective clothing .
S45:In case of accident or if you feel unwell, seek medical advice immediately (show label where possible) .
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice . | [RIDADR ]
UN 2811 6.1/PG 3
| [WGK Germany ]
3
| [RTECS ]
UQ2275500
| [HazardClass ]
6.1(a) | [PackingGroup ]
II | [HS Code ]
29339980 |
| Hazard Information | Back Directory | [General Description]
Crystalline solid or very light yellow powder. | [Reactivity Profile]
A halogenated amine and amide, acidic salt. In aqueous solution, behaves as a weak acid. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. Organic amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx). | [Air & Water Reactions]
Insoluble in water. | [Health Hazard]
SYMPTOMS: Symptoms of exposure to this compound include headache, weakness, fatigue, back, chest, neck, shoulder or extremity pain; nausea, anorexia, vomiting, abdominal pain, hyperkalemia, paresthesias, shock, dizziness, coughing, shortness of breath, depression, nervousness, flaccid paralysis of the extremities, bradycardia, flatulence, skin rash, gas pain, constipation and dyspnea. | [Fire Hazard]
Flash point data for this material are not available; however, AMILORIDE HYDROCHLORIDE(2016-88-8) is probably combustible. | [Chemical Properties]
Pale Yellow Solid | [Originator]
Midamor,Merck,UK,1971 | [Uses]
A calcium channel andsodium channel protein inhibitor | [Uses]
Na+ channel inhibitor, diuretic | [Uses]
Sodium channel blocker. Diuretic. | [Definition]
ChEBI: A hydrochloride obtained by combining amiloride with one molar equivalent of hydrochloric acid. | [Manufacturing Process]
Step A: Preparation of methyl 3-amino-5,6-dichloropyrazinoare: Methyl 3-
aminopyrazinoate (765 g, 5 mols) is suspended in 5 liters of dry benzene.
While stirring under anhydrous conditions sulfuryl chloride (1.99 liters, 3.318
g, 24.58 mols) is added over a period of 30 minutes and stirring is continued
for 1 hour. During this period, the temperature rises to about 50°C and then
begins to drop. The mixture is heated cautiously to reflux (60°C), refluxed for
5 hours and then stirred overnight at room temperature. The excess sulfuryl
chloride is distilled off at atmospheric pressure (distillation is stopped when
vapor temperature reaches 78%). The dark red mixture is chilled to 6°C. The
crystals are filtered off, washed by displacement with two 100 ml portions of
cold (8°C) benzene, then washed with 300 ml petroleum ether and dried in
vacuum at room temperature, yielding 888 g (80%) of methyl 3-amino-5,6-
dichloropyrazinoate in the form of red crystals, MP 228-230°C. The crude
product is dissolved in 56 liters of boiling acetonitrile and passed through a
heated (70-80°C) column of decolorizing charcoal (444 g). The column is
washed with 25 liters of hot acetonitrile, the combined eluate concentrated in
vacuum to about 6 liters and chilled to 5°C. The crystals that form are
filtered, washed three times with cold acetonitrile, and air dried to constant
weight, yielding 724 g (82% recovery, 66% overall) of methyl 3-amino-5,6-
dichloropyrazinoate in the form of yellow crystals, MP 230-234°C. After
additional recrystallizations from acetonitrile the product melts at 233-234°C.
Step B: Preparation of methyl-3,5diamino-6-chloropyrazinoete: In a 2-liter, 3-necked flask fitted with a a mechanical stirrer, thermometer and gas inlet tube
is placed dry dimethyl sulfoxide (1 liter). Methyl 3-amino-5,6-
dichloropyrazinoate (100 g, 0.45 mol) is added and the mixture stirred and
heated at 65°C on a steam bath until solution is effected. A stream of dry
ammonia gas is admitted to the solution with continuous stirring, over a
period of 45 minutes while the temperature is maintained at 65-70°C. The
solution is cooled to about 10°C with continuous stirring and ammonia gas is
admitted for an additional 1 1/4 hours. The yellow reaction mixture is poured,
with stirring, into cold water (2 liters) and the light yellow solid that separates
is removed by filtration, thoroughly washed with water, and dried in a vacuum
desiccator to give 82.5 g (91%) of methyl 3,5-diamino-6-chloropyrazinoate,
MP 210-212°C. Recrystallization from acetonitrile gives material melting at
212-213°C.
Step C: Preparation of the base: A 300 ml one-necked, round-bottomed flask,
equipped with a water-cooled condenser, calcium chloride tube and magnetic
stirrer is charged with anhydrous methanol (150 ml) and sodium metal (5.75
g, 0.25 g atom). When the reaction is complete, the solution is treated with
dry guanidine hydrochloride (26.3 g, 0.275 mol) and stirred for 10 minutes.
The sodium chloride that forms is removed by filtration. The solution is
concentrated in vacuum to a volume of 30 ml and the residue treated with the
product of Step B, heated one minute on a steam bath and kept at 25°C for 1
hour. The product is filtered, washed well with water, dissolved in dilute
hydrochloric acid and the free base precipitated by addition of sodium
hydroxide to give the amiloride product base, a solid which melts at 240.5-
241.5°C.
To produce the hydrochloride, the base is suspended in water (70 ml) and
treated with sufficient 6 N hydrochloric acid to dissolve the free base. The
solution is filtered and treated with concentrated hydrochloric acid (5 ml). The
hydrochloride salt (22 g, 97%) separates and is recrystallized from water (50
ml) containing concentrated hydrochloric acid (3 ml). | [Brand name]
Midamor (Merck). | [Therapeutic Function]
Diuretic | [Biological Activity]
Na + channel blocker. Defines the I 2A -amiloride sensitive and I 2B -amiloride insensitive imidazoline binding sites. Also inhibits TRPP3 channels. | [Biochem/physiol Actions]
Selective T-type calcium channel blocker and blocker of epithelial sodium channel. Selective inhibitor of urokinase plasminogen activator (uPA). | [Clinical Use]
Oedema
Potassium conservation with thiazide and loop
diuretics | [Drug interactions]
Potentially hazardous interactions with other drugs
ACE inhibitor and angiotensin-II antagonists:
increased risk of hyperkalaemia and hypotension.
Antibacterials: avoid concomitant use with
lymecycline.
Antidepressants: increased risk of postural
hypotension with tricyclics; enhanced hypotensive
effect with MAOIs.
Antihypertensives: enhanced hypotensive effect.
Ciclosporin: increased risk of hyperkalaemia and
nephrotoxicity.
Cytotoxics: increased risk of nephrotoxicity and
ototoxicity with platinum compounds.
Lithium excretion reduced
NSAIDS: increased risk of hyperkalaemia; increased
risk of nephrotoxicity; antagonism of diuretic effect.
Potassium salts: increased risk of hyperkalaemia.
Tacrolimus: increased risk of hyperkalaemia. | [Metabolism]
Amiloride is excreted unchanged in the urine. In two
studies in which single doses of 14C-Amiloride were
used, approximately 50% was recovered in urine and 40%
in the faeces within 72 hours. | [storage]
Room temperature |
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