86541-74-4 Usage
Description
Benazepril hydrochloride is a prodrug of benazeprilat, a long-acting angiotensin-converting enzyme (ACE) inhibitor. It is used in the treatment of essential hypertension and has been shown to be well-tolerated in healthy humans without significant pharmacokinetic interactions with other medications. Additionally, it is being investigated as a cardiostimulant.
Uses
Used in Pharmaceutical Industry:
Benazepril hydrochloride is used as an antihypertensive and angiotensin-converting enzyme (ACE) inhibitor for the treatment of essential hypertension. It helps lower blood pressure and is also used to treat congestive heart failure and chronic kidney disease in both human and veterinary medicine.
Used in Cardiovascular Applications:
Benazepril hydrochloride is used as a cardiostimulant under investigation, potentially offering benefits in cardiovascular health by improving heart function and overall cardiovascular system performance.
Used in Veterinary Medicine:
In veterinary medicine, benazepril hydrochloride is used as an antihypertensive and ACE inhibitor to treat hypertension, congestive heart failure, and chronic kidney disease in animals, helping to manage and improve their health conditions.
Manufacturing Process
The synthesis of benzazepril based on a benzazepinone. It started by
chlorination of lactam - 1,2,4,5-tetrahydrobenzo[b]azepin-2-one to the
dichloro derivative 3,3-dichloro-1,2,4,5-tetrahydrobenzo[b]azepin-2-one.
Catalytic reduction removed one of the gem chloro substituents to give 3-
chloro-1,2,4,5-tetrahydrobenzo[b]azepin-2-one; the halogen was then
displaced with sodium azide to give 3-azido-1,3,4,5-
tetrahydrobenzo[b]azepin-2-one. Alkylation of the amide with ethyl
bromoacetate in the presence of base yielded the ester (3-azido-2-oxo-
2,3,4,5-tetrahydrobenzo[b]azepin-1-yl)acetic acid ethyl ester. Hydrogenation
then converted the azide to an amino group to give 3-amino-2-oxo-2,3,4,5-
tetrahydrobenzo[b]azepin-1-yl)acetic acid ethyl ester. It was then resolved by
classical salt formation and crystallization. Saponification of the S enantiomer
- S-(3-amino-2-oxo-2,3,4,5-tetrahydrobenzo[b]azepin-1-yl)acetic acid ethyl
ester with sodium hydroxide afforded (3-amino-2-oxo-2,3,4,5-
tetrahydrobenzo[b]azepin-1-yl)acetic acid. Reductive alkylation of it with 2-
oxo-4-phenylbutyric acid ethyl ester and sodium cyanoborohydride gave the
desired product as 70:30 mixture of diastereoisomers. The isolation of the
predominant isomer gave benazepril. The epimerization occurred thermally
and therefore required a sufficiently high temperature. The high temperature
condition can be achieved by either using a high boiling-point solvent such as
xylene or by heating the reaction mixture under pressure to increase its
boiling-point temperature. Good results can be achieved in both polar and
non-polar solvent systems. For example, both p-xylene and ethylene glycolwater
systems are found suitable to conduct this process. The crude product
acid 3-[(1-ethoxycarbonyl)-3-phenyl-(1S)-propylamino]-2,3,4,5-tetrahydro-2-
oxo-1H-1-benzazepine-1-acetic acid was heated to reflux temperature for 30
hours in p-xylene. The mixture was cooled down to room temperature.
Solvent removal resulted in a solid, which was then dried at reduced pressure
to give a 98:2 diasteriomeric mixture as determined by HPLC, MP: 287°-
290°C. IR and 1H-NMR spectrum analysis. was confirmed the structure of
product.
Therapeutic Function
Antihypertensive
Biological Activity
Non-peptide angiotensin-converting enzyme (ACE) inhibitor. Reduces blood pressure and myocardial hypertrophy in spontaneous hypertensive rats.
Biochem/physiol Actions
Benazepril is a long-acting angiotensin converting enzyme (ACE) inhibitor.
Check Digit Verification of cas no
The CAS Registry Mumber 86541-74-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,6,5,4 and 1 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 86541-74:
(7*8)+(6*6)+(5*5)+(4*4)+(3*1)+(2*7)+(1*4)=154
154 % 10 = 4
So 86541-74-4 is a valid CAS Registry Number.
InChI:InChI=1/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+;/m1./s1
86541-74-4Relevant articles and documents
Use of convertible isocyanides for the synthesis of benazepril hydrochloride
Borase, Bhushan B,Godbole, Himanshu M,Singh, Girij P,Upadhyay, Pritesh R,Trivedi, Anurag,Bhat, Varadaraj,Shenoy, Gautham G
, (2021/04/19)
Herein, we have described a novel and concise synthesis of the potent angiotensin-converting enzyme (ACE) inhibitor, benazepril hydrochloride (7) in trifluoroethanol via an Ugi three-component reaction in shorter reaction times. The key step is the trifluoroacetic acid-mediated hydrolysis of secondary amides (4a and 4b) followed by esterification as a domino process to form corresponding ethyl ester (6). Mainly two universal convertible isocyanides (1a and 1b) were used for the synthesis of benazepril hydrochloride. Graphic abstract: [Figure not available: see fulltext.] Synopsis: An efficient synthesis of benazepril hydrochloride using Ugi three-component reaction.
An improved method for preparing of the benazepril hydrochloride and containing the pharmaceutical composition of the benazepril hydrochloride
-
, (2018/01/05)
The invention discloses an improved preparation method of benazepril hydrochloride and pharmaceutical composition containing the benazepril hydrochloride. With the adoption of the preparation method, the safety is high, the cost is low, the clean production value is high, industrial production is easy to realize, and meanwhile, the pharmaceutical composition is easy to prepare and use.
IMPROVED PROCESS FOR CRYSTALLIZATION OF BENAZEPRIL HYDROCHLORIDE
-
Page/Page column 4, (2009/04/23)
An improved process for the crystallization of benazepril hydrochloride to obtain in at least 99.8% diastereomeric purity. The process comprises making a concentrated solution of benazepril hydrochloride in ethanol and adding the resulting solution to a non-solvent diisopropyl ether.