Delapril hydrochloride
(Synonyms: 地拉普利盐酸盐) 目录号 : GC38766
Delapril Hydrochloride (Alindapril) is the hydrochloride salt form of delapril, which is a lipophilic, non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity.
Cas No.:83435-67-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Delapril Hydrochloride (Alindapril) is the hydrochloride salt form of delapril, which is a lipophilic, non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity.
The poteny of delapril is about 15 times greater than captopril and almost equal to enalaprilat in inhibiting rabbit lung ACE activity in vitro and about 10 times greater than captopril in inhibiting angiotensin I-induced contraction in isolated tissue preparations, such as rat aortic rings and rat kidney[2].
After oral administration of [14C]delapril 10 mg/kg to rats, 57% of the dose is absorbed mainly in the small intestine via the portal route and extensively metabolized by esterases to the diacid derivative M-I. Plasma levels of M-I peak within 0.4 hour of administration (maximum concentration [Cmax] 1.23 μg/mL), then decline biphasically with half-lives of 0.6 and 9.1 hours. In dogs given 10 mg/kg of [14C]delapril, 72% of the dose is absorbed. Plasma levels of M-I peak within 0.4 hour of administration (Cmax, 0.9 μg/ mL), then decline biphasically with half-lives of 0.3 and 2.8 hours. Delapril is able to inhibit plasma and tissue ACE at doses 5-10 times lower than captopril and this has also been found in in vivo experiments. Delapril has been shown to decrease heart weight, left ventricular weight, the wall to lumen ratio of small coronary arterioles, and thickness of the left ventricular wall in stroke-prone SHR, to reduce cardiac renin gene expression in SHR, and to protect perfused rat hearts against ischemia-reperfusion injury[2].
[1] Saruta T, et al. Am J Hypertens. 1991, 4(1 Pt 2):23S-28S. [2] Razzetti R, et al. Am J Cardiol. 1995, 75(18):7F-12F.
| Cas No. | 83435-67-0 | SDF | |
| 别名 | 地拉普利盐酸盐 | ||
| Canonical SMILES | CCOC([C@H](CCC1=CC=CC=C1)N[C@@H](C)C(N(C2CC3=C(C=CC=C3)C2)CC(O)=O)=O)=O.[H]Cl | ||
| 分子式 | C26H33ClN2O5 | 分子量 | 489 |
| 溶解度 | DMSO: 250 mg/mL (511.25 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.045 mL | 10.2249 mL | 20.4499 mL |
| 5 mM | 0.409 mL | 2.045 mL | 4.09 mL |
| 10 mM | 0.2045 mL | 1.0225 mL | 2.045 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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2.
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Delapril versus manidipine in hypertensive therapy to halt the type-2-diabetes-mellitus-associated nephropathy
Diabetes Res Clin Pract 2000 Feb;47(2):97-104.PMID:10670908DOI:10.1016/s0168-8227(99)00114-x.
Thirty-nine hypertensive patients with type 2 diabetes mellitus were followed under long-term treatment (mean, 20.7 months) with manidipine hydrochloride, a Ca antagonist, or Delapril hydrochloride, an ACE inhibitor, at nine institutions. Both the treatments showed similar antihypertensive effects, although slight but significantly larger decreases were observed in systolic and mean blood pressures at months 12 and 24 in the patients treated with manidipine (P < 0.02). The urinary albumin excretion index (AEI) tended to increase throughout the study in both treatment groups, but no significant difference in AEI was observed between the two treatment groups at any time point. Overt albuminuria developed in four patients on manidipine but did not appear in any of the patients on delapril. The risk of progression to overt albuminuria was significantly different between manidipine and delapril groups (P = 0.011). No increase in serum creatinine (Cr) was observed with delapril. The average excretion indexes of tubular markers such as beta2-microglobulin, alpha1-microglobulin, and NAG tended to be higher in the patients on manidipine than in those on delapril. Taken in sum, these findings suggest that the ACE inhibitor delapril is more beneficial than the Ca antagonist manidipine in the treatment of diabetic renal diseases via mechanisms other than the blood pressure regulation, partly through their different effects on tubular function. In conclusion, delapril was significantly more effective than manidipine in inhibiting progression to overt albuminuria in hypertensive type 2 diabetes mellitus patients.
Effects of Delapril hydrochloride on the myocardium of spontaneously hypertensive rats
Can J Cardiol 1994 Nov;10(9):939-43.PMID:7954031doi
Objective: To investigate the effects of long term treatment with Delapril hydrochloride (an angiotensin-converting enzyme inhibitor) on myocardial contractility and ventricular myosin isoenzymes in spontaneously hypertensive rats (SHR). Design: Delapril hydrochloride (10 mg/kg/day by mouth) was administered to 22- to 24-week-old male SHR for eight to 10 weeks. The isometric contractions of isolated left ventricular papillary muscles were observed while being perfused with Tyrode's solution (32 degrees C, pH 7.4, bubbled with 95% oxygen: 5% carbon dioxide, stimulation frequency 0.2 Hz). The left ventricular myosin isoenzymes were separated using pyrophosphate-gel electrophoresis. Main results: The mean systolic blood pressure of the delapril-treated group was significantly lower than that of the untreated control group. The mean ventricular weight was also lower in the delapril-treated than control group (mean +/- SD, untreated: 211 +/- 11 mmHg, n = 6; delapril-treated: 183 +/- 14 mmHg, n = 8, P < 0.01). The mean isometric developed tension (T) and +/-dT/dtmax of isolated left ventricular papillary muscles from the delapril-treated and untreated SHR did not differ significantly. The left ventricular myosin isoenzyme pattern obtained by pyrophosphate-gel electrophoresis, however, showed a significant shift towards VM-1 after long term delapril treatment. Conclusions: Long term treatment of SHR with Delapril hydrochloride reduced blood pressure, which was associated with regression of cardiac hypertrophy, and changed the ventricular myosin isoenzyme pattern without significantly affecting myocardial contractility.
Effect of Delapril hydrochloride on angiotensin II release from isolated rat hind legs
Eur J Pharmacol 1990 Aug 2;184(1):169-72.PMID:2209711DOI:10.1016/0014-2999(90)90678-y.
The effect of the newly developed angiotensin-converting enzyme (ACE) inhibitor, delapril hydrochrolide (CV-3317), on the release of immunoreactive angiotensin II (irAng II) from isolated rat hind legs was compared with that of captopril. Both ACE inhibitors, added to the perfusion medium (2 X 10(-9) - 10(-6) M), suppressed irAng II release in a dose-dependent manner, but the inhibition was greater with delapril than with captopril. The results provide further support for the concept that vascular tissues produce Ang II and release it in a regulated fashion. The results also suggest a possible link between the antihypertensive mechanism of ACE inhibitors, including delapril, and the suppression of vascular Ang II release.
Single oral dose pharmacokinetic interaction study of manidipine and delapril in healthy volunteers
Arzneimittelforschung 2003;53(9):627-34.PMID:14558436DOI:10.1055/s-0031-1297159.
Objective: The objective of the study was to assess potential pharmacokinetic interactions between delapril, an angiotensin conversion enzyme inhibitor, and manidipine, a calcium channel antagonist, prior to the development of a fixed combination drug product. Methods: Eighteen healthy male volunteers received a single oral dose of 10 mg manidipine dihydrochloride (CAS 89226-75-5), or 30 mg Delapril hydrochloride (CAS 83435-67-0), or both simultaneously, according to a fully balanced three-way cross-over design. The three treatments were separated by a one-week washout period. Blood samples were collected during 24 h for plasma determination of manidipine and metabolite M-XIII and/or of delapril and metabolites M1, M2 and M3, using specific LCMS/MS methods. Results: The bioavailability of manidipine and M-XIII was slightly decreased by concomitant administration of delapril (manidipine: Cmax-19% and AUC infinity-11% M-XIII: Cmax-17% and AUCt-18%). The bioavailability of delapril was not influenced by co-administration with manidipine (Cmax-7% and AUC infinity +4%). The effect on delapril pharmacologically active metabolites M1 and M3 was negligible. The inactive metabolite M2 underwent a 13% reduction of Cmax and AUC infinity. The 90% confidence intervals were confined within limits of acceptance (70-143% for Cmax and 80-125% for AUC). Mean residence times and apparent elimination half-lives were unaltered. Blood pressure and heart rate versus time profiles were similar during the three treatments. Conclusions: Simultaneous oral administration of 10 mg manidipine and 30 mg delapril does not significantly alter the pharmacokinetics of either drug or that of their principal metabolites.
Pharmacokinetics and acute effect on the renin-angiotensin system of delapril in patients with chronic renal failure
Clin Nephrol 1987 Feb;27(2):65-70.PMID:3030595doi
The acute effect on the renin-angiotensin system and the pharmacokinetic properties of delapril, a new angiotensin converting enzyme inhibitor and its active diacid metabolites (delapril diacid and 5-hydroxy delapril diacid) arising from delapril in vivo were investigated in 4 hypertensive patients with chronic renal failure (CRF: 4 males, average age 49.5 (37-64) years, mean Ccr 22.2 ml/min/1.73 m2) and 9 patients with essential hypertension (EH: 6 males, 3 females, average age 42.8 (28-61) years, mean Ccr 79.3 ml/min/1.73 m2). In CRF, following a single dose of Delapril hydrochloride (30 mg), the biological half lives (t1/2) of delapril diacid and 5-OH-delapril diacid were 4.69, 12.88 hours, the maximum serum concentration (Cmax) and the area under the plasma concentration-time curve ([AUC]24(0)) of delapril and its diacid metabolites were 414, 797 and 435 ng/ml, and 658, 6400 and 5068 ng X h/ml, respectively. In EH, the t1/2 of delapril diacid and 5-OH-delapril diacid were 1.21, 1.40 hours and the Cmax and [AUC]24(0) of delapril and its diacid metabolites were 489, 635 and 229 ng/ml, and 572, 1859 and 948 ng X h/ml, respectively. The [AUC]24(0) in CRF were significantly increased as compared with those in EH. The cumulative urinary excretions were significantly lower in CRF than in EH. The serum angiotensin converting enzyme (ACE) was markedly inhibited in both groups up to 24 hours. The plasma concentration of angiotensin II decreased in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)