| Identification | More | [Name]
Benazepril hydrochloride | [CAS]
86541-74-4 | [Synonyms]
1h-1-benzazepine-1-aceticacid,2,3,4,5-tetrahydro-3-((1-(ethoxycarbonyl)-3-phe
cgs14824a
monohydrochloride,(s-(r*,r*))-nylpropyl)amino)-2-oxo
BenazeprilHclC24H28N205.HC1
1H-1-Benzazepine-1-acetic acid, 3-(1S)-1-(ethoxycarbonyl)-3-phenylpropylamino-2,3,4,5-tetrahydro-2-oxo-, monohydrochloride, (3S)-
1H-1-Benzazepine-1-acetic acid, 3-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-, monohydrochloride, [S-(R*,R*)]-
CGS 14824A HCl
Lotensin
Lotension
Benazenprilhydrochloride
{(3S)-3-[(1S)-1-Ethoxycarbonyl-3-phenylpropylamino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-1-yl}acetic acid hydrochloride
Benazepril hydrochloride
(3S)-3-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid hydrochloride
2-((S)-3-((S)-1-ethoxy-1-oxo-4-phenylbutan-2-ylamino)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)aceticacidhydrochloride | [EINECS(EC#)]
630-414-2 | [Molecular Formula]
C24H29ClN2O5 | [MDL Number]
MFCD01668249 | [Molecular Weight]
460.95 | [MOL File]
86541-74-4.mol |
| Chemical Properties | Back Directory | [Appearance]
Crystalline Solid | [Melting point ]
188-190°C | [alpha ]
D -141.0° (c = 0.9 in ethanol) | [storage temp. ]
2-8°C | [solubility ]
DMSO: ~34 mg/mL, soluble
| [form ]
solid
| [color ]
white
| [Usage]
Used as an antihypertensive | [Merck ]
14,1031 | [InChIKey]
VPSRQEHTHIMDQM-FKLPMGAJSA-N | [SMILES]
C12=CC=CC=C1CC[C@H](N[C@H](C(=O)OCC)CCC1C=CC=CC=1)C(=O)N2CC(=O)O.Cl |&1:8,10,r| | [CAS DataBase Reference]
86541-74-4(CAS DataBase Reference) |
| Hazard Information | Back Directory | [Description]
Benazepril hydrochloride is a long-acting and effective angiotensin-converting enzyme (ACE) inhibitor used to treat essential hypertension. It is the hydrochloride salt form of benazepril, which is a prodrug of benazeprilat. After hepatic cleavage of the ester group, benazepril is converted to benazeprilat. In healthy humans, it was well tolerated and showed no phmacokinetic interactions with furosemide, hydrochlorothiazide, chlorthalidone, digoxin, cimetidine, atenolol, or naproxen. | [Chemical Properties]
This substance is a white to off-white crystalline powder. It is highly soluble in water, ethanol, and methanol with a solubility of over 100 mg/mL. | [Originator]
Ciba-Geigy (Switzerland) | [Uses]
Benazepril HCl is an angiotensin-converting enzyme (ACE) inhibitors that is commonly used as a sedative, hypnotic, and antihypertensive medication. Benazepril is used alone or together with other medicines to treat high blood pressure (hypertension). It works by reducing the levels of certain chemicals that cause blood vessels to constrict, allowing for smoother blood flow. | [Definition]
ChEBI: 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. | [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. | [Brand name]
Lotensin (Novartis);Cibacen. | [Therapeutic Function]
Antihypertensive | [General Description]
Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards | [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. | [Synthesis]
Benazepril hydrochloride is prepared through the following steps:
Step 1: Preparation of (R)-ethyl 2-hydroxy-4-phenylbutyrate using ethyl 2-oxo-4-phenylbutyrate as a raw material and cinchonidine as a chiral ligand through asymmetric catalytic hydrogenation under high pressure.
Step 2: The intermediate obtained from step 1 reacts with p-nitrobenzenesulfonyl chloride or trifluoromethanesulfonic anhydride to obtain the corresponding sulfonate.
Step 3: The sulfonate obtained from step 2 undergoes nucleophilic substitution and salt hydrolysis with (3S)-3-amino-2,3,4,5-tetrahydro-2-oxo-1H-benzazepine-1-tert-butyl acetate to obtain benazepril hydrochloride.
This procedure has been described in detail in documents such as CN110835319A, US4785089, WO02076375, EP206993, and CN105061312. | [storage]
Store at-20°C | [Mode of action]
The mechanism of action of benazepril is to inhibit the activity of the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II Label, thereby alleviating a series of symptoms caused by angiotensin (elevated blood pressure, increased excitatory heart rate caused by vasodilation, insufficient cardiac output, etc.). | [References]
https://www.novartis.com/us-en/sites/novartis_us/files/lotrel.pdf
https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a216253b-27cb-42ef-b5a8-67fb05aafb88
Extrapyramidal side effect of donepezil hydrochloride in an elderly patient DOI: 10.1097/MD.0000000000019443
Use of convertible isocyanides for the synthesis of benazepril hydrochloride DOI: 10.1007/s12039-021-01892-8 |
|
|