2609-46-3 Usage
Description
AMILORIDE is a potassium-sparing diuretic that exhibits moderate activity. It is not an antagonist of aldosterone but inhibits the reabsorption of sodium ions and reduces the excretion of potassium ions. It is a monocarboxylic acid amide with N-carbamimidoylpyrazine-2-carboxamide substituted by amino groups at positions 3 and 5 and a chloro group at position 6.
Uses
Used in Pharmaceutical Industry:
AMILORIDE is used as a diuretic for treating conditions like cardiac insufficiency and hypertension. It helps in reducing the amount of salt and water the body retains, thereby lowering blood pressure and alleviating the workload on the heart.
Used in Combination Therapy:
AMILORIDE is used in combination with thiazide diuretics or loop diuretics to enhance their effectiveness and prevent hypokalemia, a condition characterized by low potassium levels in the blood.
Used as an Epithelial Sodium Channel Blocker:
AMILORIDE is used as an epithelial sodium channel blocker, which helps in reducing the absorption of sodium ions in the body and promoting their excretion through urine. This action contributes to the diuretic effect and helps in managing fluid balance and blood pressure.
Therapeutic Function
Diuretic
Clinical Use
Amiloride, another potassium-sparing diuretic, is an aminopyrazine structurally related to triamterene as an open-chain analogue. Similar to triamterene, it interferes with
the process of cationic exchange in the distal convoluted tubule by blocking luminal sodium channels. It blocks the reabsorption of sodium ion and the secretion of
potassium ion. It has no effect on the action of aldosterone. Oral amiloride is approximately 50% absorbed, with
a duration of action of 10 to 12 hours, which is slightly longer than that for triamterene. Although triamterene is extensively metabolized, approximately 50% of amiloride
is excreted unchanged. Renal impairment can increase its elimination half-life. Like triamterene, amiloride combined with a thiazide or loop diuretic is used to treat edema
or hypertension.
Synthesis
Amyloride, N-amidino-3,5-diamino-6-chloropirazincarboxamide (21.5.18), is
synthesized from 5,6-diaminouracil, which upon reaction with glyoxal transforms into a
pyrazineopyrimidine derivative (21.5.14), which decomposes upon further reaction with a
strong alkaline, forming 3-aminopirazin-2-carboxylic acid (21.5.15). This is esterified into
the corresponding methyl ester (21.5.16), and subsequently treated with sulfonyl chloride
and ammonia, which gives the methyl ester of 3,5-diamino-6-chloropirazin-2-carboxylic
acid (21.5.17). Reacting this with guanidine gives amyloride (21.5.18).
Enzyme inhibitor
This potassium-sparing diuretic (FW = 229.63 g/mol; CAS 2016-88-8;
Absorbance at 10 mg/mL (water) = 642 at 212 nm, 555 at 285 nm, and 617
at 362 nm; pKa = 8.7; Soluble in hot water (50 mg/mL), yielding a clear,
yellow-green solution), also known as MK 870, Midamor?, and 3,5-
diamino-6-chloro-N- (diaminomethylene) pyrazine-2-carboxamide, is an
epithelial sodium channel (or ENaC) blocker used to manage hypertension
and congestive heart failure (1-4). Two classes of Na+ transporters are
sensitive to this drug: (a) the conductive Na+ entry pathway found in
electrically high resistance epithelia and (b) a Na+-H+ electroneutral
exchange system found in certain leaky epithelia, such as the renal
proximal tubule. Amiloride exhibits a Ki value of <1 μM for the kidney
transporter and approximately 1 mM in the colon. Midamor is a potassium-
conserving (antikaliuretic) drug that possesses weak (compared with
thiazide diuretics) natriuretic, diuretic, and antihypertensive activity. Like
other potassium-conserving agents, amiloride may cause hyperkalemia
(i.e., serum K+ levels >5.5 mEq/L), which, if uncorrected, can be fatal.
Amiloride-induced hyperkalemia occurs in ~10% of patients, when used
without a kaliuretic diuretic. This complication is more frequent in patients
showing evidence of renal impairment and diabetes mellitus. When used
along with a thiazide diuretic in patients without these complications, the
risk of Amiloride-induced hyperkalemia drops to 1-2%. Amiloride is not
metabolized by the liver and is instead excreted unchanged by the kidney.
Amiloride displaces both adenosine A1 receptor agonist and antagonist
binding with a Ki value in the low micromolar range, when assayed in calf
brain membranes. Inhibition is counteracted by NaCl and protons.
Amiloride (IC50 = 0.25 mM) and 5- (N-ethyl-N-isopropyl) amiloride (IC50 =
0.11 mM) also inhibit coxsackievirus B3 RNA polymerase in a single-
nucleotide incorporation assay, although the argument that amiloride
competes with incoming nucleoside triphosphates is unconvincing. A high-
fidelity RNA dependent CVB3 RNA polymerase (RdRp) variant is
amiloride-resistant.
Check Digit Verification of cas no
The CAS Registry Mumber 2609-46-3 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 2,6,0 and 9 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 2609-46:
(6*2)+(5*6)+(4*0)+(3*9)+(2*4)+(1*6)=83
83 % 10 = 3
So 2609-46-3 is a valid CAS Registry Number.
InChI:InChI=1/C6H8ClN7O/c7-2-4(9)13-3(8)1(12-2)5(15)14-6(10)11/h(H4,8,9,13)(H4,10,11,14,15)
