98048-97-6 Usage
Angiotensin converting enzyme inhibitor
Angiotensin converting enzyme inhibitor (ACEI) is a therapeutic drug that has been widely attached importance to by scholars both at home and abroad in recent years to resist hypertension and kidney damage. The WHO/ISH1999 guidelines for the treatment of hypertension have included ACEI in the 6 major drugs for the treatment of hypertension. It inhibits vasodilatation by inhibiting renin angiotensin system, reducing adrenaline released from adrenal nerve terminals, reducing endothelin formation and inhibiting bradykinin decomposition and inactivation and angiectasis. It also promotes the synthesis of prostaglandins with vasodilating effect, reduces aldosterone secretion, decreases the retention of water and sodium, and increases renal blood flow. It has a significant protective effect on kidney. Fosinopril is the third generation of ACEI. After oral administration, it will be hydrolyzed into an active Fosinoprilat in the gastrointestinal mucosa and liver. The latter can inhibit angiotensin-converting enzyme, reduce the production of angiotensin II, therefore decreasing the peripheral resistance, decreasing aldosterone secretion and increasing plasma renin activity. Fosinopril also inhibits the degradation of bradykinin and reduces vascular resistance, thus reducing the effect of blood pressure.
This product expands arteries and veins at the same time. This not only reduces peripheral vascular resistance (afterload), but also reduces capillary wedge pressure (preload), thereby improving cardiac output and can be used for congestive heart failure. Oral absorption is rapid and complete and the absorption rate is about 36%, which is not affected by food. The time to reach peak is not related to the dose, usually in 3 hours. The half-life is about 12 hours, and 14 hours for the patients with heart failure. The plasma protein binding rate of Fosinoprilat is more than 95%, which can be secreted by milk. The single dose will take effect 1 hour after oral administration and the maximum effect can be achieved 2~4 hours after oral administration. The effect can be maintained for 24 hours. 44% ～ 50% of this product is removed from the kidneys, 46% to 50% can be excreted from the intestines after removal of the liver. In hemodialysis and peritoneal dialysis, the scavenging amount of this product is only 2% and 7% of urine clearance.
Figure1 The structural formula of fosinopril
Precaution
Cautious use in the following cases: ①Autoimmune diseases (such as severe systemic lupus erythematosus):The chances of leukocyte or granulocytic reduction are increased at this time. ② Myelosuppression. ③ Cerebral or coronary artery insufficiency: ischemia can be aggravated by lowering blood pressure. ④ ]hyperkalemia. ⑤ Renal dysfunction: it will increase blood potassium, reduce leukocyte and granulocytic, and lead to the retention of the product.⑥ Liver dysfunction: reducing the metabolism of this product in the liver.⑦ Those with strict diet limiting sodium salt or dialysis treatment: The first dose of this product may result in sudden and severe hypotension.
The administration of this product may result in the cases as follows: ①The concentration of blood urea nitrogen and creatinine is increased, which is often temporary. It is easy for this case to occur when there is a rapid decline in blood pressure in patients with kidney or severe hypertension.②There will be an occasional increase of serum liver enzyme. ③ A slight increase in blood potassium, especially in those with renal dysfunction.?
The follow-up examination during the administration of this product: ①For patients with renal dysfunction or leukocyte deficiency, the white blood cell count and classification count are checked every 2 weeks in the first 3 months, and then checked regularly thereafter. ② Urine protein examination, once a month.?
The antihypertensive effect of this product is the same in the standing position and the supine position.
For those who have used diuretics, they should stop using diuretics for 2~3 days before using this product. But those with severe or malignant hypertension are exceptional. They should use this product at a low dose and carefully increase the dose under close observation.?
Medication should be stopped during the period of vascular edema, and adrenaline is injected subcutaneously and hydrocortisone is injected intravenously.
FDA is classified as grade C for the safety of pregnancy.
If in the middle and late pregnancy, the drug is D grade.
Application
Light, medium and severe hypertension: It can be prioritized as the first drug, and can also be used when other antihypertensive drugs have poor curative effect.
Myocardial ischemia: it can reduce the oxygen consumption of myocardium, increase the oxygen supply of myocardium, double the treatment of myocardial ischemia, reduce the frequency of angina pectoris and the dosage of nitrate.?
Treatment of heart failure: it can be used as the first choice by dilating blood vessels and reducing sodium retention.
Prohibited use
It is forbidden for those who are allergic to this product or other angiotensin converting enzyme inhibitors.
Those with solitary kidney, transplant kidney, bilateral renal artery stenosis and renal dysfunction are forbidden to use this product.
Interaction
This product can reduce the decrease of potassium induced by thiazide diuretics. Its combination with potassium diuretic or potassium supplement can increase the risk of hyperkalemia. If this kind of drug should be used at the same time, the patient's serum potassium needs to be monitored regularly. Acid resistant drugs may affect the absorption of this product. If taken, it must be separated at least two hours.Non steroidal anti-inflammatory drugs can affect the effect of this product on lowering blood pressure. But at the same time, the use of this product and steroidal anti-inflammatory drugs (including aspirin) do not increase the other clinical adverse reactions. Treatment with lithium can increase the concentration of serum lithium. The combined use of beta blockers, Methyldopa, calcium antagonists and diuretics can increase the efficacy of antihypertensive drugs.
Originator
Fosinopril Sodium,Bristol-Myers Squibb
Uses
mydriatic,
Definition
ChEBI: A phosphinate ester-containing N-acyl derivative of (4S)-cyclohexyl-L-proline. It is used for the treatment of hypertension and heart failure. A pro-drug, it is hydrolysed in vivo to the corresponding phosphin
nc acid, fosinoprilat, which is the active metabolite.
Brand name
Monopril (Bristol-Myers Squibb).
Check Digit Verification of cas no
The CAS Registry Mumber 98048-97-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 9,8,0,4 and 8 respectively; the second part has 2 digits, 9 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 98048-97:
(7*9)+(6*8)+(5*0)+(4*4)+(3*8)+(2*9)+(1*7)=176
176 % 10 = 6
So 98048-97-6 is a valid CAS Registry Number.
InChI:InChI=1/C30H46NO7P/c1-4-28(33)37-30(22(2)3)38-39(36,18-12-11-15-23-13-7-5-8-14-23)21-27(32)31-20-25(19-26(31)29(34)35)24-16-9-6-10-17-24/h5,7-8,13-14,22,24-26,30H,4,6,9-12,15-21H2,1-3H3,(H,34,35)/t25-,26+,30?,39?/m1/s1
98048-97-6Relevant articles and documents
Preparation methods of antihypertensive Fosinopril sodium and key intermediate thereof
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, (2017/12/14)
The invention relates to preparation methods of an antihypertensive Fosinopril sodium and a key intermediate thereof trans-4-phenyl-L-proline suitable for industrial production. Synthesis of the key intermediate trans-4-phenyl-L-proline has high chiral selectivity, and the method is simple and easy to operate.
Process for the preparation of fosinopril and intermediates thereof
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Page/Page column 7, (2012/06/18)
The present invention relates to a process for the preparation of intermediates useful in the synthesis of [1[S(R)],2α,4β]-4-cyclohexyl-1-[[[2-methyl-1-oxypropoxy) propoxy](4-phenylbutyl phosphinyl]acetyl]-L-proline, and the synthesis thereof, in particular as sodium salt (fosinopril sodium).
Process for the preparation of fosinopril and intermediates thereof
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Page/Page column 7, (2011/01/11)
Process for the preparation of intermediates useful in the synthesis of [1[S(R)],2α,4β]-4-cyclohexyl-1-[[[(2-methyl-1-oxypropoxy) propoxy](4-phenylbutyl) phosphinyl]acetyl]-L-proline, and the synthesis thereof, in particular as sodium salt.
