Benazepril
Benazepril Basic information
- Product Name:
- Benazepril
- Synonyms:
-
- 2-[(4s)-4-[[(1s)-1-ethoxycarbonyl-3-phenyl-propyl]amino]-5-oxo-6-azabicyclo[5.4.0]undeca-7,9,11-trien-6-yl]acetic acid
- genazepril
- BENAZEPRIL HCL, RELATED COMPOUND B(3S)-3-[[(1R)-1-(ETHOXYCARBONYL)-3-PHENYLPROPYL]AMINO]-2,3,4,5-TETRAHYDRO-2-OXO-1H-1-BENAZAPINE-1-ACETIC ACID, MONOHYDROCHLORIDE USP STANDARD
- BENAZEPRIL HCL, MM(CRM STANDARD)
- BENAZEPRIL HCL, USP STANDARD
- BENAZEPRIL HCL USP(CRM STANDARD)
- BENAZEPRIL MM
- BENAZEPRIL MM(CRM STANDARD)
- CAS:
- 86541-75-5
- MF:
- C24H28N2O5
- MW:
- 424.49
- Product Categories:
-
- API
- Antihypertensive
- Active Pharmaceutical Ingredients
- Mol File:
- 86541-75-5.mol
Benazepril Chemical Properties
- Melting point:
- 148-149°
- alpha
- D -159° (c = 1.2 in ethanol)
- Boiling point:
- 691.2±55.0 °C(Predicted)
- Density
- 1.26±0.1 g/cm3(Predicted)
- storage temp.
- 2-8°C
- solubility
- Soluble in DMSO
- pka
- 3.73±0.10(Predicted)
- form
- Solid
- color
- White to off-white
- BCS Class
- 1
- CAS DataBase Reference
- 86541-75-5(CAS DataBase Reference)
Safety Information
- Safety Statements
- 22-24/25
- Hazardous Substances Data
- 86541-75-5(Hazardous Substances Data)
Benazepril Usage And Synthesis
Originator
Lotensin,Novartis
Uses
Benazepril Free base is a non-sulfhydryl ACE inhibitor.
Definition
ChEBI: A benzazepine that is benazeprilat in which the carboxy group of the 2-amino-4-phenylbutanoic acid moiety has been converted to the corresponding ethyl ester. It is used (generally as its hydrochloride salt) as a prodrug for the angiotensin-converting enzy e 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.
Therapeutic Function
Antihypertensive
Enzyme inhibitor
This ACE-directed pro-drug (FWfree-acid = 424.50 g/mol; CAS 86541-75-5), also known as 3-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-2,3,4,5- tetrahydro-2-oxo-(S-(R*,R*))-1H-1-benzazepine-1-acetic acid, Lotensin and CGS 14824A, is rapidly metabolized to its diacid benazeprilat (CGS 14831; FWfree-diacid = 396.44 g/mol), the latter a potent, long-acting inhibitor of peptidyl-dipeptidase A, or angiotensin I-converting enzyme, IC50 = 1.7 nM. Lotensin is used to treat hypertension, congestive heart failure, and chronic renal failure. The antihypertensive effects of benazepril begin as early as 30 min after a single dose, and those effects during consecutive dosing are also sustained for 24 h with a lesser diurnal variation in blood pressure
Benazepril Preparation Products And Raw materials
Raw materials
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Benazepril(86541-75-5)Related Product Information
- PHENYL VALERATE
- Phenylhydrazine
- Glycine
- 3,4'-DIAMINODIPHENYLMETHANE
- 1,1'-Carbonyldiimidazole
- Propyl gallate
- Lithium diisopropylamide
- Propyl butyrate
- ALTRENOGEST
- Carbonyl iron powder
- S-ATBA
- Benazepril Related Compound G
- Benazepril hydrochloride
- NICKEL CARBONYL
- Benazepril Related Compound D
- Benazepril Related Compound F
- Hydrocortisone
- CORTISONE