What Is Imidapril?

The imidapril compound is obtained as colorless crystals from ethyl acetate-n-hexane, and has a melting point of 139-140 ° C. [] D20-71.7 ° (C = 0.5, ethanol), chemical name is (-)-(4S) -3-[(2S) -2 [(1S) -1-ethoxycarbonyl-3-phenylpropyl ] Aminopropanoyl] -1-methyl-2-oxoimidazoline-4-carboxylic acid. Clinically, it belongs to angiotensin-converting enzyme inhibitor, a prodrug, and is used for hypertension. ^[1]

Chinese name: Midapril
Foreign name: Imidapril
CAS number: 89371-37-9

Molecular formula: C20H27N3O6
Density: 1.266 g / cm3
Molecular weight: 405.44500

Brief Introduction to Midapride

Midapril Basic Information

Chinese name

Chinese alias: (-)-(4S) -3-[(2S) -2 [(1S) -1-ethoxycarbonyl-3-phenylpropyl] aminopropionyl] -1-methyl-2-oxo Imidazoline-4-carboxylic acid; (4S) -3-[(2S) -2- [N-[(1S) -1- (ethoxycarbonyl) -3-phenylpropyl] amino] propanoyl] -1 -Methyl-2-oxoimidazolidine-4-carboxylic acid;

English name: imidapril;

English alias: (4S) -3-[(2S) -2-[[((2S) -1-ethoxy-1-oxo-4-phenylbutan-2-yl] amino] propanoyl] -1-methyl-2-oxoimidazolidine -4-carboxylic acid; (S) -3- (N-((S) -1-Ethoxycarbonyl-3-phenylpropyl) -L-alanyl) -1-methyl-2-oxoimidazoline-4-carboxylic acid; Imidapril [BAN : INN]; Imidapril HCl; (4S) -3-<(2S) -2- <N-<(1S) -1- (Ethoxycarbonyl) -3-phenylpropyl> amino> propionyl> -1-methyl-2-oxoimidazolidine -4-carboxylic acid;

CAS number: 89371-37-9

Molecular formula: C20H27N3O6

Structural formula:

Molecular weight: 405.44500

Exact mass: 405.19000

PSA: 116.25000

LogP: 1.14290 ^[1]

Physical properties of midapride

Appearance and properties: white solid

Density: 1.266 g / cm3

Melting point: 195-197 ° C

Boiling point: 577ºC at 760 mmHg

Flash point: 302.8ºC

Storage conditions: -20ºC Freezer ^[1]

Midapril Safety Information

Packing level: II

Danger category: 8

Dangerous Goods Transport Code: 1759

Danger category code: R22; R34

Safety instructions: S26; S36 / 37/39 ^[1]

Midapril production method

In the presence of potassium carbonate, -bromophenylbutyric acid ethyl ester was used for N-alkylation of alanine benzyl ester, and then the benzyl group was removed by hydrogenolysis. The resulting free acid was N-hydroxysuccinimide. After esterification, it is reacted with imidazoline ester in tert-butanol solution of potassium tert-butoxide. The product is hydrolyzed and acidified to obtain midapril hydrochloride. ^[1]

Another preparation method is to first esterify 3-benzyloxycarbonyl-2-oximidazoline-4-carboxylic acid with tert-butanol, then methylate N with methyl iodide, and remove the benzyl at the 3-position by hydrogenolysis. Oxycarbonyl group to free N at the 3-position of the imidazoline ring, which can be acylated with -p-toluenesulfonylpropionyl chloride, and the acylated product is reacted with ethyl -aminophenylbutyrate to obtain midaprol The tert-butyl ester product is hydrolyzed and acidified to give midapril hydrochloride. ^[1]

Midapride uses

Angiotensin-converting enzyme inhibitors, prodrugs, used for hypertension. ^[1]

Pharmacological effects of midapril

1. Angiotensin-converting enzyme (ACE) inhibitor, an ester prodrug, which is not high in activity and is hydrolyzed into dicarboxylic acid compounds (Imidaprilat) in the blood and has activity; This active form with a carboxyl (-COOH) or thiol (-SH) group is a group that binds to the Zn of the enzyme.

2. Diastolic blood vessels (including arteries and veins), lower blood pressure, strong and long-lasting varieties. The characteristic is that the antihypertensive effect is exact, the action lasts for a long time, and the medicine can be used once a day, and the incidence of adverse reactions, especially dry cough, is low.

3. It is rapidly distributed in all tissues except the central nervous system after oral administration, and reaches the maximum concentration in most tissues after 2 hours of administration, and the concentration in liver, kidney and lung is higher than that in plasma. 25.5% is excreted from the urine with a half-life of 8 hours.

4. White crystals. Soluble in methanol, soluble in water, slightly soluble in absolute ethanol, and almost insoluble in ethyl acetate, chloroform, and ethanol. MP205 ~ 206 ° C, melting and decomposing at the same time.

5. Toxicology (carcinogenicity, mutagenicity and reproductive toxicity): Rats and mice were orally administered the product (10mg / kg daily and 30mg / kg daily) for 18 months and 4 months, respectively. No carcinogenicity was found. effect. Bacterial reverse transformation test, mouse micronucleus test, chromosome aberration and gene mutation test showed no mutagenic effect. Reproductive toxicity studies in rats and rabbits showed no teratogenic and lethal effects. ^[2-3]

Pharmacokinetics of Midapril

Healthy adult men take 10 mg orally. The concentration of the active metabolite midaprila in the plasma reaches a peak value (15ng / ml) in about 6 to 8 hours. The elimination half-life is 8 hours. The total excretion rate in urine is 24.5% of the dose . Healthy adults take 10 mg orally for 7 consecutive days. The plasma concentration of midalpril reaches a steady state after 3 to 5 days without accumulation in the body. However, the plasma concentration of patients with renal dysfunction is compared with healthy adults. It can be seen that the half-life is prolonged and the peak plasma concentration is increased. ^[3]

Midapril indication

1. Essential hypertension

2. Secondary hypertension caused by renal parenchymal disease. ^[2]

Midapril taboo

1. Patients with a history of allergies to this product

2. Patients with angioedema induced by other angiotensin-converting enzyme inhibitors

3. Patients treated with glucose sulfate sulfate adsorber

4. Patients undergoing hemodialysis with acrylonitrile sodium allylsulfonate membrane (AN69a)

5. Prohibited for pregnant or likely pregnant women. ^[2-3]

Midapril precautions

1. Use with caution in patients with aortic stenosis, cerebral or coronary insufficiency.

2. The dosage should be adjusted according to the individual effect according to the principle of individualization.

3. Breastfeeding women use this product with caution. When medication is necessary, breastfeeding should be discontinued.

4. When taking this product, the elderly should start with a low dose (such as 2.5mg), and adjust the dosage interval according to the patient's situation.

5. Use this product with caution in patients with severe renal dysfunction, patients with bilateral renal artery stenosis, patients with cerebrovascular disorders, and elderly patients.

6. Patients with severe hypertension, patients undergoing hemodialysis, patients taking diuretics (especially at the beginning of medication), and more severe patients undergoing low-salt therapy must start medication at low doses.

7. Occasionally, dizziness, faltering, etc. may be caused by the action of reducing blood pressure. Therefore, attention should be paid to dangerous operations such as aerial work.

8. It is best not to use this medicine within 24 hours before surgery. ^[2-3]

Midapril adverse reactions

The more common ones are cough, dizziness, headache, fatigue, orthostatic hypotension, and rashes, all of which are slightly transient. Occasionally angioedema of the face, tongue, and throat with dyspnea, severe thrombocytopenia, worsened renal insufficiency, or elevated liver aminotransferases. Angiotensin-converting enzyme inhibitors have been reported to cause various blood cell decreases. The incidence of dry cough was significantly lower than enalapril, cilapril, and lisinopril. ^[2-3]

Dosage of Midap

Generally, adults take 5 to 10 mg of midapril hydrochloride once a day. Appropriate increase or decrease according to age symptoms. However, patients with severe hypertension, hypertension with renal dysfunction, and patients with renal parenchymal hypertension are best started with 2.5 mg. This product should be used under the guidance of a doctor. ^[2]

Midapril Note:

For patients with severe renal dysfunction whose creatinine clearance is below 30ml / min, or whose serum creatinine is above 3mg / dl, the drug should be used with caution, or the dose should be halved, or the interval between drugs should be extended. (Due to the delay in excretion, excessive reduction in blood pressure and deterioration of renal function may occur) ^[2]

Interactions of other drugs with midapril

1. Used with high-dose diuretics can cause severe hypotension.

2. The combined use of midalpril and potassium-preserving diuretics (spironone, amfenatine, etc.) or potassium supplements (potassium chloride, etc.) can increase serum potassium concentration.

3. The combination of midapril and lithium preparation (lithium carbonate) may cause lithium poisoning.

4. For patients treated with diuretics (trichloromethazine, dihydrochlorothiazide, etc.), taking this product for the first time will enhance the antihypertensive effect.

5. Combining with non-steroidal anti-inflammatory drugs (indomethacin) will weaken the antihypertensive effect of this product

6. Other antihypertensive drugs (hypertensive drugs, nitric acid preparations, etc.) can also enhance the antihypertensive effect of this product. ^[3]