| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
CV 5975 (40 g; 3.5-29 h) was kinetically resolved by lipase PN to generate (R)-4 (ee value 64%), which was then converted to CV-5975 by mesylation, SN2 reaction and deprotection reaction, with a total yield of 25% [1]. CV 5975 (40 g; 48 h) was asymmetrically reduced to α-oxyester 3 in the form of baker's yeast to generate (R)-4 (ee value 61%), with a yield of 46%, which is suitable for the synthesis of CV-5975 [1]. CV 5975 (10⁻⁸ M; 60 min) can effectively inhibit the crude angiotensin-converting enzyme extracted from the lungs of albino male rabbits, with an IC₅₀ value of 3.1 × 10⁻⁹ M, and its activity is much higher than that of its three stereoisomers [2]. CV 5975 (20 min) effectively and competitively inhibited partially purified rabbit lung ACE, with an IC50 of 3.1 × 10-9 M, Ki of 2.6 × 10-9 M, and a high-affinity steady-state Ki* of 4.4 × 10-12 M [4].
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| ln Vivo |
CV 5975 (0.3–3 mg/kg; intravenous or oral; single dose) potently and persistently inhibited angiotensin I-induced pressor response in male Sprague-Dawley rats. After intravenous administration of 0.3 mg/kg, the inhibition rate was >90% and lasted for at least 2 hours. After oral administration of 3 mg/kg, the inhibition rate lasted for up to 7 hours, making it the longest-lasting piperidine derivative tested [2]. CV 5975 (10 mg/kg; oral; single dose) produced a mild but significant hypotensive effect in normotensive Wistar Kyoto rats, lasting for 10 hours [3]. CV 5975 (1–10 mg/kg; oral; once daily for 2 weeks) showed a dose-dependent sustained hypotensive effect in spontaneously hypertensive rats, with increased potency and duration after repeated administration, and produced significant, tissue-wide ACE inhibition, which was associated with a decrease in blood pressure [3]. CV 5975 (1-10 mg/kg; orally; single dose) produced a potent, sustained and dose-dependent antihypertensive effect in a rat model of bilateral renal artery clipping, with a maximum blood pressure reduction of 65 mmHg at an oral dose of 10 mg/kg, lasting for more than 24 hours [3]. CV 5975 (1-10 mg/kg; orally; single dose) also produced a dose-dependent antihypertensive effect in a rat model of unilateral renal artery clipping, with a significant reduction in blood pressure at an oral dose of 10 mg/kg, lasting for more than 10 hours [3]. CV 5975 (1-10 mg/kg; orally; single dose; once daily for 2 weeks) produced a mild dose-dependent antihypertensive effect in a rat model of hyporeninemia-induced DOCA/salt, with repeated daily administration not enhancing the efficacy [3]. CV 5975 (0.3–1 mg/kg; orally; single dose) produced a sustained antihypertensive effect in a hypertensive canine model with bilateral renal clipping, reducing systolic and diastolic blood pressure by approximately 40 mmHg at a dose of 1 mg/kg[3]. CV 5975 (0.3–1 mg/kg; orally) effectively inhibited the angiotensin I-induced pressor response in normotensive beagle dogs at oral doses of 0.3 and 1 mg/kg, with inhibition rates exceeding 90%, and a longer duration of action than enalapril[4].
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| Animal Protocol |
Animal/Disease Models:Sprague-Dawley mice (male, 300-400 g) [2]
Doses: 0.3 mg/kg (intravenous); 3 mg/kg (oral) Route of Administration: Intravenous or oral; single dose Experimental Results: After intravenous injection of 0.3 mg/kg, the angiotensin I-induced pressor response was inhibited by 96% at 10 minutes, 99% at 30 minutes, 93% at 60 minutes, and 91% at 120 minutes. Among all piperidine derivatives tested, it had the longest duration of ACE inhibition, recovering to 50% of the control group more than 4 hours after intravenous injection of 0.3 mg/kg. After oral administration of 3 mg/kg, the angiotensin I-induced pressor response was inhibited by 70% at 20 minutes, 84% at 1 hour, 91% at 3 hours, 88% at 5 hours, and 84% at 7 hours. Animal/Disease Models:Wistar Kyoto rats (male, 20 to 22 weeks old)[3] Doses: 10 mg/kg Route of Administration: Oral; single dose Experimental Results: Mean arterial blood pressure was slightly but significantly reduced, with the largest decreases being 9 mmHg at 5 hours, 8 mmHg at 7 hours, and 10 mmHg at 10 hours. Blood pressure returned to pre-drug levels 24 hours after administration. Animal/Disease Models:Spontaneously Hypertensive Rats (Male, 20 to 22 weeks old)[3] Doses: 1 mg/kg; 3 mg/kg; 10 mg/kg Route of Administration: Oral; Single dose; Once daily for 2 weeks Experimental Results: Blood pressure decreased by 10 to 35 mmHg in a dose-dependent manner, with the maximum effect reaching 5 to 10 hours and lasting for more than 24 hours. After repeated administration, the antihypertensive efficacy and duration were enhanced, with the maximum effect observed on day 7; after 1 week of drug withdrawal, blood pressure was still significantly lower than that of the control group (202 mmHg in the 1 mg/kg group, 203 mmHg in the 3 mg/kg group, and 202 mmHg in the 10 mg/kg group), and returned to the control level after 2 weeks of drug withdrawal. After repeated daily administration for 1 week, ACE activity in all tested tissues (plasma, aorta, kidney, lung, brain) was inhibited. Animal/Disease Models:Wistar rats (male, initial age 6 weeks, used 4 to 6 weeks after surgery for bilateral single-clip renal hypertension, systolic blood pressure 160 to 240 mmHg) [3] Doses: 1 mg/kg; 3 mg/kg; 10 mg/kg Route of Administration: Oral; single dose Experimental Results: Dose-related, significant, and sustained decrease in blood pressure was observed; the maximum blood pressure reduction (approximately 65 mmHg) was achieved 7 to 10 hours after administration, and blood pressure remained below pre-administration levels for more than 24 hours after administration. Animal/Disease Models:Wistar rats (male, initial age 6 weeks, used 4 to 6 weeks after surgery for hypertension with a single kidney and a single clipped kidney, systolic blood pressure 160 to 240 mmHg) [3] Doses: 1 mg/kg; 3 mg/kg; 10 mg/kg Route of Administration: Oral; single dose Experimental Results: Blood pressure decreased in a dose-dependent manner; at a dose of 10 mg/kg, the effect was observed 3 hours after administration, and blood pressure remained lower than the control level for more than 10 hours. Animal/Disease Models:Wistar rats (male, initial age 6 weeks, used 4 to 6 weeks after surgery for low-renin DOCA/salt hypertension, systolic blood pressure 160 to 240 mmHg) [3] Doses: 1 mg/kg; 3 mg/kg; 10 mg/kg Route of Administration: Oral; single dose; once daily for 2 weeks Experimental Results: A slight and sustained hypotensive effect was produced after a single dose. Repeated daily administration reduced arterial blood pressure in a dose-dependent manner without enhancement; the hypotensive effect disappeared within 24 hours after each discontinuation of the drug. Animal/Disease Models:Beagle (male, 13 to 16 kg, used 2 to 5 weeks after surgery for bilateral single-cylinder hypertension)[3] Doses: 0.3 mg/kg; 1 mg/kg Route of Administration: Oral; Single dose Experimental Results: Moderate and sustained reduction in systemic blood pressure was observed within 1 hour of administration, with effects lasting for more than 10 hours. At a dose of 1 mg/kg, both systolic and diastolic blood pressure decreased by approximately 40 mmHg, and there was a tendency for heart rate to increase (but this was not statistically significant). Animal/Disease Models:Sprague-Dawley rats (male, 300-400 g) [4] Doses: 0.03 mg/kg (intravenous); 0.3 mg/kg (intravenous); 3 mg/kg (oral); 10 mg/kg (oral) Route of Administration: Intravenous or oral Experimental Results: Intravenous injection of 0.3 mg/kg maximally inhibited the angiotensin I (AI) pressor response and had a longer duration of action than enalapril. The recovery half-life (T1/2) of 0.3 mg/kg was approximately 5 hours, and the ID50 was 0.07 mg/kg during the 7-hour observation period. Oral administration of 3 mg/kg enhanced the bradykinin (BK)-induced hypotensive response, resulting in a blood pressure reduction of 31.6 mmHg at 1 hour, 32.0 mmHg at 3 hours, 28.6 mmHg at 5 hours, and 24.8 mmHg at 7 hours. The inhibitory effect on the AI-induced hypertensive response persisted for more than 24 hours, with an ID50 of 0.07 mg/kg. At an oral dose of 10 mg/kg, the 24-hour observation period was 1.8 mg/kg. Animal/Disease Models:Beagle (sex or male, 13-15 kg) [4] Doses: 0.3 mg/kg; 1 mg/kg Route of Administration: Oral Experimental Experimental Results: Compared with the oral dose of enalapril 0.3 mg/kg, this product inhibited the angiotensin I (AI)-induced pressor response by more than 90%, and the duration of inhibition was longer. Compared with the oral dose of enalapril 1 mg/kg, this product inhibited the AI-induced pressor response by more than 90%, and the duration of action was longer than 24 hours. The effect of the oral dose of enalapril 1 mg/kg disappeared after 24 hours. |
| References |
|
| Molecular Formula |
C22H31N3O5S
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|---|---|
| Molecular Weight |
449.56
|
| CAS # |
100277-62-1
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
OC(CN1C2=CC=CC=C2SC[C@@H](C1=O)N[C@H](C(O)=O)CCCCC3CCNCC3)=O
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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 | 2.2244 mL | 11.1220 mL | 22.2440 mL | |
| 5 mM | 0.4449 mL | 2.2244 mL | 4.4488 mL | |
| 10 mM | 0.2224 mL | 1.1122 mL | 2.2244 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.
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