| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
Benazeprilat (formerly known as CGS-14831), the active metabolite of the benazepril, is a potent inhibitor of angiotensin converting enzyme (ACE) with IC50 of 0.28 nM in plasma from dog.
| Targets |
Benazeprilat is an angiotensin-converting enzyme (ACE) inhibitor. A radioligand binding study showed that benazeprilat was a more potent in vitro inhibitor of ACE compared with other drugs in this class and their active components including captopril, enalaprilat, lisinopril and perindoprilat [1].
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| ln Vitro |
Benazeprilat was identified as a strong inhibitor of ACEs. In vitro radioligand binding studies demonstrated that benazeprilat exhibited greater potency in inhibiting ACE compared to other ACE inhibitors and their active metabolites, such as captopril, enalaprilat, lisinopril, and perindoprilat [1].
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| ln Vivo |
A good antihypertensive effect can be achieved by combining benazeprilat (10 mg/kg, intravenous injection) with amlodipine (0.5 mg/kg, intravenous injection) [2]. Oral benazepril (0.7 mg/kg) dramatically alters the kinetics of the systemic RAAS peptide, leading to a marked reduction in AII and ALD and an increase in PRA and AI [3].
However, following oral administration of the prodrug benazepril to rats (1-45 mg/kg), significant ACE inhibition was demonstrated in several tissues. The highest distribution of the active metabolite, benazeprilat, was observed in the kidney, followed by the lungs and aorta, with the lowest levels found in the brain and testes [1]. |
| Enzyme Assay |
The determination of ACE inhibitory potency was performed using radioligand binding studies. These studies compared the in vitro inhibitory activity of benazeprilat against ACE with that of other ACE inhibitors and their active metabolites, including captopril, enalaprilat, lisinopril, and perindoprilat [1].
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| Animal Protocol |
Animal/Disease Models: Male SHR (14-16 weeks old, 250-350 grams) [2].
Doses: 10 mg/kg Route of Administration: IV; one time/day for 2 days Experimental Results: A hypotensive effect occurs. Animal/Disease Models: Beagle dog (12.0-19.5 kg) [3]. Doses: 0.7 mg/kg Route of Administration: Orally, one time/day for 5 days. Experimental Results: Effects of systemic RAAS peptides. The tissue distribution of benazeprilat was assessed in rats. Following oral administration of its prodrug, benazepril, at doses ranging from 1 to 45 mg/kg, the animals were evaluated to determine the extent of ACE inhibition across different tissues [1]. The tissue distribution of benazeprilat was assessed in rats. Following oral administration of its prodrug, benazepril, at doses ranging from 1 to 45 mg/kg, the animals were evaluated to determine the extent of ACE inhibition across different tissues [1]. |
| ADME/Pharmacokinetics |
Benazeprilat is the active metabolite of the prodrug benazepril. Following oral administration and absorption, the ethyl ester group of benazepril is cleaved, converting it into benazeprilat [1].
- The conversion of benazepril to benazeprilat occurs mainly in the liver via enzymatic hydrolysis and is complete within 4 hours [1]. - After a single 10 mg oral dose of benazepril in healthy volunteers, the maximum plasma concentration (Cmax) of benazeprilat was 492 pmol/g, with a corresponding area under the curve (AUC0-24) of 2649 pmol/g·h [1]. - For a 20 mg dose of benazepril, the Cmax of benazeprilat was 972 pmol/g, and the AUC0-24 was 4690 pmol/g·h [1]. - The time to reach maximum plasma concentration (Tmax) for benazeprilat is approximately 1.5 hours after a 10 mg dose and 1.0 hours after a 20 mg dose of benazepril [1]. - Benazeprilat is highly bound (approximately 95%) to serum proteins [1]. - The elimination of benazeprilat from plasma is biphasic, with an initial half-life (t1/2) of about 3 hours and a terminal half-life of approximately 22 hours in healthy volunteers. This long terminal phase likely reflects its strong binding to ACE with slow elimination [1]. - Renal clearance is the main route of elimination for benazeprilat, occurring at a rate of approximately 1.4 L/h [1]. Approximately 20% of an oral benazepril dose is excreted renally as benazeprilat [1]. - In older subjects (65-80 years), the AUC and terminal half-life of benazeprilat increased significantly by approximately 20-40% compared to younger individuals [1]. - In patients with severe renal failure, there was a large increase in the AUC of benazeprilat [1]. - In patients with liver cirrhosis, although the conversion of benazepril to benazeprilat may be slowed, the overall bioavailability of benazeprilat is not affected [1]. |
| Toxicity/Toxicokinetics |
The incidence of cough, a common adverse event associated with ACE inhibitors, was reported at a similar rate in patients receiving benazepril (2%) compared to those given placebo (1%) in an initial clinical safety review. In a large general practice study of 16,987 patients taking benazepril, cough was reported in 3.5% of patients [1].
- Angioneurotic edema, a class effect of ACE inhibitors, was reported in approximately 0.2% of patients in a safety meta-analysis. Cases with benazepril were mild and reversible [1]. - In the ACCOMPLISH trial, peripheral edema occurred at a higher rate in patients treated with benazepril plus amlodipine compared to those taking benazepril plus HCTZ (e.g., in those with normal kidney function: 31% vs. 13.1%) [1]. - Hyperkalemia (defined as a potassium level ≥0.5 mEq/l above normal) occurred at a similar incidence between benazepril- and placebo-treated patients (5% vs. 4% for increases within the normal range) [1]. - Other adverse events such as headache, fatigue, dizziness, and nausea were generally experienced at a similar rate in the benazepril and placebo groups [1]. |
| References |
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| Additional Infomation |
Benazeprilat is a benzodiazepine compound with the chemical name 1,3,4,5-tetrahydro-2H-1-benzodiazepine-2-one, in which the hydrogen atom bonded to the nitrogen atom is replaced by a carboxylmethyl group, and the 3-pro-S hydrogen is replaced by the amino group of (2S)-2-amino-4-phenylbutyric acid. It is an angiotensin-converting enzyme inhibitor, and its monoester prodrug, Benazeprilat, is used to treat hypertension and heart failure. It is an EC 3.4.15.1 (peptidyl dipeptidase A) inhibitor. It is a benzodiazepine compound belonging to the dicarboxylic acid and lactam class of compounds. Benazeprilat is an angiotensin-converting enzyme inhibitor. The mechanism of action of Benazeprilat is as an angiotensin-converting enzyme inhibitor. The physiological effect of Benazeprilat is achieved by lowering blood pressure. Benazeprilat is the active metabolite of Benazeprilat, a carboxyl-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive effects. The prodrug Benazeprilat is metabolized in the liver to Benazeprilat, which competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive effect of angiotensin II, leading to vasodilation. Benazeprilat also reduces adrenal cortex aldosterone secretion for angiotensin II, thereby increasing sodium excretion and consequently increasing water excretion.
See also: Benazeprilat hydrochloride (active ingredient). Benazeprilat is the active diacid metabolite of the prodrug benazepril. Benazepril itself has very low inhibitor activity; it is converted to benazeprilat after administration and absorption [1]. - Benazeprilat is unsuitable for oral administration owing to poor absorption [1]. |
| Molecular Formula |
C22H24N2O5
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|---|---|
| Molecular Weight |
396.443
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| Exact Mass |
396.169
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| CAS # |
86541-78-8
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| Related CAS # |
Benazeprilat-d5;1279033-05-4
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| PubChem CID |
5463984
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| Appearance |
White to off-white solid powder
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| Density |
1.34 g/cm3
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| Boiling Point |
711.3ºC at 760 mmHg
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| Melting Point |
270-272ºC
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| Flash Point |
384ºC
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| Index of Refraction |
1.643
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| LogP |
2.55
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
29
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| Complexity |
590
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C(N1C(=O)[C@@H](N[C@H](C(=O)O)CCC2C=CC=CC=2)CCC2C=CC=CC1=2)C(=O)O
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| InChi Key |
MADRIHWFJGRSBP-ROUUACIJSA-N
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| InChi Code |
InChI=1S/C22H24N2O5/c25-20(26)14-24-19-9-5-4-8-16(19)11-13-17(21(24)27)23-18(22(28)29)12-10-15-6-2-1-3-7-15/h1-9,17-18,23H,10-14H2,(H,25,26)(H,28,29)/t17-,18-/m0/s1
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| Chemical Name |
(2S)-2-[[(3S)-1-(carboxymethyl)-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]amino]-4-phenylbutanoic acid
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| Synonyms |
Benazeprilat CGS 14831 CGS-14831 CGS14831
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL | |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL | |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00835367 | COMPLETEDWITH RESULTS | Drug: Amlodipine-benazepril 10 mg-20 mg capsules Drug: Lotrel® 10 mg-20 mg capsule |
Healthy | Teva Pharmaceuticals USA | 2004-03 | Phase 1 |
| NCT00836576 | COMPLETED | Drug: Benazepril HCl 40 mg Tablets Drug: Lotensin® 40 mg Tablets |
Healthy | Teva Pharmaceuticals USA | 2001-02 | Phase 1 |
| NCT00836537 | COMPLETED | Drug: Benazepril HCl 40 mg Tablets Drug: Lotensin® 40 mg Tablets |
Healthy | Teva Pharmaceuticals USA | 2001-03 | Phase 1 |
| NCT00834977 | COMPLETEDWITH RESULTS | Drug: Amlodipine-benazepril 10 mg-20 mg capsules Drug: Lotrel® 10 mg-20 mg capsule |
Healthy | Teva Pharmaceuticals USA | 2004-04 | Phase 1 |
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