Benazepril HCl (formerly CGS 14824A; CGS-14824-A; Briem; Cibacène; Cibacen; Labopal; Lotensin), the hydrochloride salt of Benazepril which is a prodrug that can be metabolized to its active form benazeprilat, is a potent angiotensin I converting enzyme (ACE) inhibitor that has been widely used primarily in treatment of hypertension. The mechanism of action of thie drug is to prevent the catalytic conversion of angiotensin I to angiotensin II and in turn causes vasodilation and an increase in capillary blood volume. Benazepril hydrochloride dose-dependently inhibits the increase in the blood pressure caused by continuous norepinephrine infusion in spontaneously hypertensive rats and suppresses in seizures.

Physicochemical Properties

Molecular Formula	C24H28N2O5.HCL
Molecular Weight	460.95
Exact Mass	460.176
CAS #	86541-74-4
Related CAS #	Benazepril;86541-75-5;Benazepril-d5 hydrochloride;1279026-26-4
PubChem CID	5362123
Appearance	White to off-white solid powder
Boiling Point	691.2ºC at 760 mmHg
Melting Point	188-190°C
Flash Point	371.8ºC
LogP	3.831
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	10
Heavy Atom Count	32
Complexity	619
Defined Atom Stereocenter Count	2
SMILES	CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]2CCC3=CC=CC=C3N(C2=O)CC(=O)O.Cl
InChi Key	VPSRQEHTHIMDQM-FKLPMGAJSA-N
InChi Code	InChI=1S/C24H28N2O5.ClH/c1-2-31-24(30)20(14-12-17-8-4-3-5-9-17)25-19-15-13-18-10-6-7-11-21(18)26(23(19)29)16-22(27)28;/h3-11,19-20,25H,2,12-16H2,1H3,(H,27,28);1H/t19-,20-;/m0./s1
Chemical Name	(3S)-3-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid hydrochloride
Synonyms	CGS 14824A HCl; CGS14824A; Briem; CGS-14824-A;CGS-14824A;CGS-14824 A; Cibacène; Cibacen; Labopal; Lotensin
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In vitro activity: Benazepril, an angiotensin converting enzyme inhibitor, which is a medication used to treat high blood pressure. Target: angiotensin converting enzyme (ACE) Benazepril is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.
ln Vivo	Benazepril hydrochloride (3 or 10 mg/kg/d, p.o. for 14 days) dose-dependently inhibits the increase in the blood pressure caused by continuous norepinephrine (NE) infusion in spontaneously hypertensive rats (SHR) and suppresses in seizures induced by a monoamine oxidase inhibitor, tranylcypromine in NE infused SHR. Benazepril hydrochloride (30 mg/kg p.o.) decreases the triglyceride and total cholesterol levels in normotensive rats. Benazepril hydrochloride (3 mg/kg s.c.) causes a significant decrease in aortic atherosclerosis without reducing hypercholesterolemia in cholesterol-fed rabbits. Benazepril hydrochloride (100 mg/kg p.o.) shows no effect on the urine volume and urinary excretion of electrolytes but decreases PSP excretion in normotensive rats. Benazepril hydrochloride (10 mg/kg p.o.) inhibits the increase in the excretion of urinary protein in DOCA/salt spontaneously hypertensive rats. Benazepril Hydrochloride administration corrects systemic hypertension and significantly reduces angiotensin II and aldosterone in cats with experimentally induced or spontaneously occurring chronic renal failure. Benazepril hydrochloride administration reduces serum creatinine and urinary protein concentration in cat with experimentally induced or spontaneously occurring chronic renal failure. Benazepril hydrochloride significantly decreases blood pressure, angiotensin II and aldosterone and, increases upon discontinuation of administration to the pre-administration levels in a canine remnant kidney model of chronic renal failure.
Animal Protocol	3 or 10 mg/kg/d, p.o. for 14 days Rats
References	Arzneimittelforschung.1991 Jun;41(6):602-7;J Vet Med Sci.2007 Oct;69(10):1015-23.
Additional Infomation	Benazepril hydrochloride is a hydrochloride salt resulting from the reaction of benazepril with 1 mol eq. of hydrogen chloride. It is used as a prodrug for angiotensin-converting enzyme inhibitor benazeprilat in the treatment of hypertension and heart failure. It has a role as an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor. It contains a benazepril(1+). Benazepril Hydrochloride is the hydrochloride salt of benazepril, a carboxyl-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, benazepril is metabolized to its active form benazeprilat. Benazeprilat 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. Benazeprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow. See also: Benazepril (has active moiety); Benazeprilat (has active moiety); Amlodipine besylate; benazepril hydrochloride (component of) ... View More ...

Solubility Data

Solubility (In Vitro)

DMSO:92 mg/mL (199.6 mM) Water:19 mg/mL (41.2 mM) Ethanol:92 mg/mL (199.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 55 mg/mL (119.32 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1694 mL	10.8472 mL	21.6943 mL
	5 mM	0.4339 mL	2.1694 mL	4.3389 mL
	10 mM	0.2169 mL	1.0847 mL	2.1694 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.