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| | Quinapril hydrochloride Basic information |
| | Quinapril hydrochloride Chemical Properties |
| Melting point | 120-130°C | | alpha | D23 +14.5° (c = 1.2 in ethanol) (Klutchko); D25 +15.4° (c = 2 in methanol) (Goel, Krolls) | | storage temp. | 2-8°C | | solubility | H2O: >10mg/mL | | form | solid | | color | white | | Water Solubility | H2O: >10mg/mL | | InChIKey | IBBLRJGOOANPTQ-ZKASTLJSNA-N | | SMILES | N1(C(=O)[C@H](C)N[C@H](C(=O)OCC)CCC2C=CC=CC=2)CC2C(=CC=CC=2)C[C@H]1C(=O)O.Cl |&1:3,6,28,r| | | CAS DataBase Reference | 82586-55-8(CAS DataBase Reference) |
| Safety Statements | 22-24/25 | | WGK Germany | 2 | | RTECS | NW7176000 | | HS Code | 2933492250 | | Storage Class | 6.1C - Combustible acute toxic Cat.3
toxic compounds or compounds which causing chronic effects | | Hazard Classifications | Repr. 2
STOT RE 1 | | Hazardous Substances Data | 82586-55-8(Hazardous Substances Data) | | Toxicity | Freely sol in aq solvents. LD50 in male, female mice, rats (mg/kg): 1739, 1840, 4280, 3541 orally; 504, 523, 158, 107 i.v. (Kaplan, 1989) |
| | Quinapril hydrochloride Usage And Synthesis |
| Chemical Properties | White Crystalline Solid | | Uses | Antihypertensive;Dopamine receptor agonist | | Uses | Quinapril is an angiotensin converting enzyme (ACE) inhibitor. Antihypertensive. | | Uses | Quinapril hydrochloride has been used as an angiotensin-converting enzyme (ACE) inhibitor to study its effects on renal tubular epithelial cell proliferation in human renal tubular epithelial cells. It has also been used as an ACE inhibitor to evaluate its effects on the expression of angiotensin II (AII) in patient-derived Atheroma samples. | | Definition | ChEBI: Quinapril hydrochloride is a hydrochloride resulting from the reaction of equimolar amounts of quinapril and hydrogen chloride. A prodrug for quinaprilat hydrochloride (by hydrolysis of the ethyl ester to the corresponding carboxylic acid), it is used as an angiotensin-converting enzyme inhibitor (ACE inhibitor) for the treatment of hypertension and congestive heart failure. It has a role as an antihypertensive agent and an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor. It contains a quinapril(1+). | | Brand name | Accupril (Pfizer); Quinapril (Lupin); Quinapril (Ranbaxy)
. | | General Description | Quinapril hydrochloride,(S)-[(S)-N-[(S)21-carboxy3-phenylpropyl]alanyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid 1-ethyl ester hydrochloride(Acuretic), forms the diacid quinaprilate in thebody. It is more potent than captopril and equipotent to theactive form of enalapril. | | Biochem/physiol Actions | Quinapril is a short-acting angiotensin converting enzyme (ACE) inhibitor. | | Synthesis | The general procedure for the synthesis of (S)-2-((S)-2-(((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino)propanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride from quinapril benzyl ester maleate was as follows: 1.73 g (3.29 mmol) of quinapril benzyl ester obtained in Example 6 (IlIc, R = Bn) was dissolved in 40 ml of ethyl acetate and about 1 ml of dry HCl was added.The hydrogenation reaction was carried out at 15-20 °C and atmospheric pressure (using a hydrogen balloon) with the addition of 5% Pd/C catalyst (about 100 mg). The progress of the reaction was monitored by LC-MS and after complete consumption of the feedstock, the catalyst was removed by filtration and the filtrate was concentrated. Grinding with methyl tert-butyl ether (MTBE) afforded the target product (S)-2-((S)-2-(((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino)propanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride as a colorless powder in the yield of 1.40 g (90% yield) with a purity of >98% by LC-MS (MH+ 439).1H NMR (showing two rotary isomers) data were as follows: δ 1.18, 1.25 (2t, 3H, OCH2CH3), 1.52 (2d, 3H, CH3), 2.08-2.30 (m, 2H, PhCH2CH2), 2.62, 2.78 (2m, 2H, PhCH2), 3.10-3.35 (m, 2H , H-4), 3.80, 3.93 (2m, 1H, NCHC=O), 4.14, 4.21 (2m, 2H, OCH2), 4.45-4.90 (3m, 3H, Hi, H-i', H-3), 5.15 (m, 1H, NHCHCH3), 7.15-7.35 (m, 9H, ArH), 9.80 (wide m, 2H , NH2), 12.80 (wide m, 1H, COOH). Quinapril hydrochloride can be further purified by ethyl acetate/toluene mixed solvent crystallization as described by S. Klutchko et al. (J. Med. Chem. 1986, 29, 1953-1961). | | References | [1] Patent: WO2014/202659, 2014, A1. Location in patent: Page/Page column 22
[2] Patent: WO2004/54980, 2004, A1. Location in patent: Page 25;13;16 |
| | Quinapril hydrochloride Preparation Products And Raw materials |
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