[CAS NO. 82586-52-5] Moexiprilhydrochloride
PRODUCTS SPECIFICATIONS [82586-52-5]
DESCRIPTION [82586-52-5]
Overview
| MDL | MFCD00940481 |
|---|---|
| Molecular Weight | 535.03 |
| Molecular Formula | C27H35ClN2O7 |
| SMILES | O=C([C@H]1N(C([C@@H](N[C@H](C(OCC)=O)CCC2=CC=CC=C2)C)=O)CC3=C(C=C(OC)C(OC)=C3)C1)O.Cl |
Summary
Moexipril hydrochloride (RS-10085) is an orally active inhibitor of angiotensin-converting enzyme ( ACE ), and becomes effective by being hydrolyzed to moexiprila (hydrochloride). Moexipril hydrochloride exhibits antihypertensive and neuroprotective effects [1] - [4] .
IC50 & Target
IC50: 2.1 nM (purified ACE from rabbit lung), 1.75 nM (ACE in rat plasma) [3]
In Vitro
Moexipril hydrochloride is devoid of anti-inflammatory properties and has no effect on platelet function
[2]
.
Moexipril hydrochloride hydrolyzes to Moexiprilat, and Moexiprilat inhibits ACE in guinea pig serum as well as on purified ACE from rabbit lung with IC
50
s of 2.6 and 4.9 nM, respectively
[2]
.
Moexipril hydrochloride (0.01 nM-0.1 mM) exhibits high potency against both plasma ACE and purified ACE from rabbit lung, with IC
50
s of 2.7 mM and 0.165 mM, respectively
[3]
.
Moexipril hydrochloride (0-100 μM, 24 h) significantly reduced the percentage of damaged neurons in a dose-dependent manner
[4]
.
Moexipril hydrochloride (0-100 μM, 24 h) significantly attenuates Fe
2+/3+
-induced neurotoxicity
[4]
.
Moexipril hydrochloride dose not cause significant changes in the percentage of apoptotic neurons
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Moexipril hydrochloride can not cross the blood-brain barrier
[1]
.
Moexipril hydrochloride (3 mg/kg, 30 mg/kg and 10 mg/kg, respectively; p.o.; once daily; 5 days) exhibits the a dose-dependent and antihypertensive effects in renal hypertensive rats, spontaneously hypertensive rats and perinephritic hypertensive dogs, respectively
[3]
.
Moexipril hydrochloride (0.3 mg/kg, i.p.) significantly reduces the infarct area on the mouse brain surface in NMRI mice
[4]
.
Moexipril hydrochloride (0.1 mg/kg, i.p.) significantly attenuates the cortical infarct volume in Long-Evans rats
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Spontaneously hypertensive rats [3] |
| Dosage: | 30 mg/kg |
| Administration: | Oral gavage; once daily; 5 days |
| Result: |
Caused a progressive lowering of mean blood pressure from pretreatment values of 180 +/- 7 mmHg to a trough on day 4 of 127 +/- 4 mmHg.
Dose-dependently decreased arterial blood pressure, and inhibited plasma and tissue ACE activity. |
| Animal Model: | Renal hypertensive rats [3] |
| Dosage: | 0.03-10 mg/kg |
| Administration: | Oral gavage; once daily; 5 days |
| Result: |
Caused a dose-dependent decrease in blood pressure with a threshold dose of 0.3 mg/kg.
Lowered mean blood pressure by about 70 mmHg of 3 mg/kg. |
| Animal Model: | Perinephritic hypertensive dogs [3] |
| Dosage: | 10 mg/kg |
| Administration: | Oral gavage; once daily; 5 days |
| Result: |
Caused a drop of mean blood pressure by 25 mmHg from pre-treatment control, which persisted for 24 h, by a rapid onset and a long duration of action.
|
| Animal Model: | NMRI mice (male, Permanent focal ischemia) [4] |
| Dosage: | 0, 0.03, 0.3, and 3 mg/kg |
| Administration: | Intraperitoneal injection (1 h before middle cerebral artery occlusion) |
| Result: | Significantly reduced the infarct area on the mouse brain surface with a dose of 0.3 mg/kg, and other doses were not effective. |
| Animal Model: | Long-Evans rats (male, Permanent focal ischemia) [4] |
| Dosage: | 0, 0.01, 0.1 mg/kg |
| Administration: | Intraperitoneal injection (1 h before middle cerebral artery occlusion) |
| Result: | Significantly attenuated the cortical infarct volume from 114.4 to 98.2 mm as compared to non-treated animals in a dose of 0.01 mg/kg, without reducing the infarct volume of the rat brain at dosages >0.01 mg/kg. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00835042 | Teva Pharmaceuticals USA |
Healthy
|
October 2003 | Phase 1 |
| NCT00990301 | Paddock Laboratories, Inc. |
Healthy
|
Phase 1 | |
| NCT00588302 | Mayo Clinic|UCB Pharma |
Primary Biliary Cirrhosis
|
June 2003 | Phase 2 |
| NCT00992862 | Paddock Laboratories, Inc. |
Healthy
|
Phase 1 | |
| NCT00834067 | Teva Pharmaceuticals USA |
Healthy
|
October 2003 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 250 mg/mL ( 467.26 mM ; Need ultrasonic)
H 2 O : 100 mg/mL ( 186.91 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8691 mL | 9.3453 mL | 18.6905 mL |
| 5 mM | 0.3738 mL | 1.8691 mL | 3.7381 mL |
| 10 mM | 0.1869 mL | 0.9345 mL | 1.8691 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 50 mg/mL (93.45 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (3.89 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (3.89 mM); Clear solution
References
- [1] Chrysant, S.G. and G.S. Chrysant, Pharmacological and clinical profile of moexipril: a concise review. J Clin Pharmacol, 2004. 44(8): p. 827-36.
- [2] Friehe H, et al. Pharmacological and toxicological studies of the new angiotensin converting enzyme inhibitor moexipril hydrochloride. Arzneimittelforschung. 1997 Feb. 47(2):132-44.
- [3] Edling, O., et al., Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril. J Pharmacol Exp Ther, 1995. 275(2): p. 854-63.
- [4] Ravati A, et al. Enalapril and moexipril protect from free radical-induced neuronal damage in vitro and reduce ischemic brain injury in mice and rats. Eur J Pharmacol. 1999 May 28;373(1):21-33.
Synonyms