 Home > Encyclopedia > Cilazapril

Cilazapril

Cilazapril structure

CAS No:
88768-40-5
Formula:
C22H31N3O5
Chemical Name:
Cilazapril
Synonyms:
6H-Pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid,9-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]octahydro-10-oxo-,(1S,9S)-;6H-Pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid,9-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]octahydro-10-oxo-,[1S-[1α,9α(R*)]]-;(1S,9S)-9-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]octahydro-10-oxo-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid;Cilazapril;Ro 31-2848;Yipingshu;Vascace;Inhibace;856439-81-1
Categories:
Active Pharmaceutical Ingredients > Circulatory System Drugs

Description

Cilazapril is a angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and congestive heart failure.Target: ACECilazapril is a new nonthiol group containing angiotensin converting enzyme (ACE) inhibitor. Cilazapril has been investigated in more than 4000 patients with all degrees of hypertension, as well as in the special patient groups such as the elderly, renally impaired, and patients with concomitant diseases, such as congestive cardiac failure or chroni

Solid

Cilazapril is a pyridazinodiazepine resulting from the formal condensation of the carboxy group of cilazaprilat with ethanol. It is a drug used in the treatment of hypertension and heart failure. It has a role as a prodrug, an antihypertensive agent and an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor. It is an ethyl ester, a pyridazinodiazepine and a dicarboxylic acid monoester. It derives from a Cilazaprilat.|Cilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure. It belongs to the angiotensin-converting enzyme inhibitors (ACE inhibitors) class of drugs. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. It is branded as Inhibace in Canada and other countries, Vascace and Dynorm in a number of European countries, among many other names. None of these varieties are available in the United States.|Cilazapril Anhydrous is the anhydrous form of the pyridazine angiotensin-converting enzyme (ACE) inhibitor cilazapril with antihypertensive activity. As a prodrug cilazapril is rapidly metabolized in the liver to cilazaprilat; cilazaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II, resulting in vasodilation. Cilazaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.|One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors) used for hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat.

Cilazapril Basic Attributes

Molecular Weight：

417.5

Exact Mass：

417.50

EC Number：

279-694-4

UNII：

8Q9454114Q

DSSTox ID：

DTXSID1048629

NCI Thesaurus Code：

C76134

ATC Code：

C09AA08|C - Cardiovascular system

Characteristics

PSA：

99.18000

XLogP3：

1.86220

Appearance：

Solid

Density：

1.26g/cm3

Melting Point：

95-97°C

Boiling Point：

598.1ºC at 760 mmHg

Flash Point：

315.5ºC

Refractive Index：

1.591

Water Solubility：

Water (25 ºC) 0.5 g/100 mL

Storage Conditions：

2-8°C

Vapor Pressure：

3.73E-15mmHg at 25°C

Safety Information

wgk germany：

safety instructions：

22-24/25

RTECS Number：

MJ9650200

GHS Classification：

|Warning|H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]|P201, P202, P281, P308+P313, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Toxicity

Toxicity Summary：

Limited data are available with regard to overdosage in humans. The most likely manifestations are hypotension, which may be severe, hyperkalaemia, hyponatraemia and renal impairment with metabolic acidosis. Treatment should be mainly symptomatic and supportive.

Protein Binding：

Maximum ACE inhibition is greater than 90% after 1 to 5 mg cilazapril. Maximum ACE inhibition is 70 to 80% after 0.5 mg cilazapril. Dose proportionality is observed following the administration of 1 to 5 mg cilazapril. Apparent non-proportionality is observed at 0.5 mg reflective of the binding to ACE. The higher doses of cilazapril are associated with longer duration of maximum ACE inhibition.

Drug Information

Drug Indication：

Cilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure.|FDA Label

Pharmacology：

Cilazapril inhibits the production angiotensin II. By doing so, it decreases sodium and water reabsorption (via aldosterone) and it decreases vasoconstriction. The combined effect of this is a decrease in vascular resistance, and therefore, blood pressure. The absolute bioavailability of cilazaprilat after oral administration of cilazapril is 57% based on urinary recovery data. (The absolute bioavailability of cilazaprilat after oral administration of cilazaprilat is 19%.) Ingestion of food immediately before the administration of cilazapril reduces the average peak plasma concentration of cilazaprilat by 29%, delays the peak by one hour and reduces the bioavailability of cilazaprilat by 14%. These pharmacokinetic changes have little influence on plasma ACE inhibition.

MeSH：

A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. (See all compounds classified as Angiotensin-Converting Enzyme Inhibitors.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

Absorption：

Maximum plasma concentrations of cilazaprilat are reached within two hours after administration of cilazapril.|Cilazaprilat is eliminated unchanged by the kidneys. The total urinary recovery of cilazaprilat after intravenous administration of 2.5 mg is 91%.|Total clearance is 12.3 L/h and renal clearance is 10.8 L/h. The total urinary recovery of cilazaprilat following the oral administration of 2.5 mg cilazapril is 52.6%.

Biological Half-Life：

Half-lives for the periods 1 to 4 hours and 1 to 7 days after the intravenous administration of 2.5 mg cilazaprilat are 0.90 and 46.2 hours respectively.

Mechanism of Action：

Cilazapril is a pyridazine ACE inhibitor. It competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. As angiotensin II is a vasoconstrictor and a negative feedback mediator for renin activity, lower angiotensin II levels results in a decrease in blood pressure, an increase in renin activity, and stimulation of baroreceptor reflex mechanisms. Kininase II, an enzyme which degrades the vasodilator bradykinin, is identical to ACE and may also be inhibited.

MeSH Entry Terms：

Cilazapril

Cilazapril Use and Manufacturing

Uses

An ACE inhibitor.Hydrolyzed in vivo to the active diacid metabolite (Cilazaprilat). Antihypertensive

Use Classification：

Pharmaceuticals

Computed Properties

Molecular Weight:417.5
XLogP3:0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:9
Exact Mass:417.22637110
Monoisotopic Mass:417.22637110
Topological Polar Surface Area:99.2
Heavy Atom Count:30
Complexity:608
Defined Atom Stereocenter Count:3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes