111470-99-6 Usage
Description
Different sources of media describe the Description of 111470-99-6 differently. You can refer to the following data:
1. Amlodipine (generic name Amlodipine Besylate) is a class of calcium channel blockers. One of the amlodipine product on the market is Norvasc?.
Amlodipine functionalizes by the dilation of blood vessels and the improvement of blood flow, which lead to lowered blood pressure. Thereby, it is used to treat high bold pressure (hypertension). Lowering high blood pressure also reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions, and kidney problems. Amlodipine is also used to prevent certain types of chest pains (angina), which may help to increase the ability to exercise and decrease the frequency of angina attacks. Amlodipine can be used to treat coronary artery disease (CAD) including chronic stable angina, vasospastic angina, and angiographically documented CAD.
2. Anilodipine besylate is a new, once-daily, dihydropyridine calcium antagonist useful in
the treatment of hypertension and angina.
Mechanism of action
Amlodipine Besylate is a dihydropyridine calcium antagonist that prevents the transmembrane influx of calcium ions into the vascularsmooth and cardiacmuscle.It attaches to both dihydropyridine and non-dihydropyridine binding sites. The contractile manners of cardiac and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine Besylate inhibits calcium ion influx across cell membranes selectively, with a superior effect on vascular smooth muscle cells than on cardiac muscle cells.
Clinical Use
Amlodipine besylate (ADB) is an important secondgeneration calcium channel blocker that belongs to the dihydropyridine family. It is used for the treatment of hypertension and angina. It is more selective for arterial vascular smooth muscle than for the cardiac tissue. It is approved for the treatment of hypertension and for variant and stable angina and may also be used for dilated cardiomyopathy. ADB has ameliorating effects on the plasma and myocardial catecholamine levels and significantly reduces calcium deposition. It has a negative inotropic effect on the heart that results in a decrease in heart work load.
https://baqai.edu.pk/baqaiassets/bjhs//admin/articlefiles/1525325965upl0.pdf
side effects
1. Heart Failure
Calcium-channel blockers are normally avoided in patients with heart failure but ADB has not been found to have any adverse effects on morbidity or mortality in patients with severe heart failure. Therefore, it may be a suitable treatment option for angina pectoris or hypertension in such patients. However, a study on hypertensive patients found that ADB was less effective than the diuretic chlorthalidone in the prevention of heart failure.
2. Porphyria
Although there have been reports of the successful use of ADB in patients with porphyria, some studies have reported the occurrence of acute exacerbation in such patients.
3. Miscellaneous Adverse Effects
A number of other adverse events occurring in response to the regular use of ADB in 1091 patients with hypertension have been reported. Around 12% (128) patients stopped the intake of the drug due to the appearance of adverse effects. The most common reported adverse effects include ankle edema, flushing, headache, skin rash, and fatigue.
Interaction with Combination Drugs
The evaluation of pharmacokinetic interactions between Amlodipine Besylate(ADB), valsartan and hydrochlorothiazide revealed no clinically relevant interactions. Similarly, combination of ADB and olmesartan medoxomil is also known to have no impact on the pharmacokinetic profiles of individual drugs. Concomitant use of ADB and atorvastatin in patients with hypertension and dyslipidemia has shown to be well tolerated without any adverse pharmacodynamic interaction. The use of triple combination i.e. ADB + Olmesartan Medoxomil + hydrochlorothiazide has also demonstrated to be safe .
References
[1] http://www.webmd.com/drugs/2/drug-5891/amlodipine-oral/details
[2] https://www.drugs.com/amlodipine.html
[3] https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b4b30c56-7403-4f69-9a8e-3d82a37e8bc5#section-1
Chemical Properties
White Crystalline Solid
Originator
Pfizer (USA)
Uses
Different sources of media describe the Uses of 111470-99-6 differently. You can refer to the following data:
1. A dihydropyridine calcium channel blocker. Used as an antianginal and antihypertensive
2. Angiotensin II inhibitor prodrug, antihypertensive
3. Amlodipine besylate is a L-type calcium channel blocker which may be used for the treatment of angina pectoris and hypertension. Amlodipine also inhibits growth of human epidermoid carcinoma A431 cells and has antireproductive effects in male rats.
Definition
ChEBI: The benzenesulfonate salt of amlodipine.
Manufacturing Process
2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-
methoxycarbonyl-6-methyl-1,4-dihydropyridine (amlodipine) was prepared
from 2-(phthalimidoaminoethoxy)acetoacetate, 2-chlorobenzaldehyde and
methyl-3-aminocrotonate under refluxing in ethanol for 24 hours. The
ketoester was prepared by the method of Troostwijk and Kellog (JCS Chem.
Comm., 1977, p.932). Methyl-3-aminocrotonate can be prepared by known
method. Phthalimido-amino-protecting group was removed using hydrazine
hydrate in ethanol at the reflux temperature.
Although amlodipine is effective as the free base, in practice it is best
administered form of a salt of a pharmaceutically acceptable acid.
Benzensulphonic salt of amlodipine was prepared as follows: Amlodipine base
(65.6 g, 0.161 mols) was slurried in industrial methylated spirit (denatured
alcohol, 326.4 ml) and cooled to 5°C. Benzensulphonic acid (26.2 g, 0.168
mols) was dissolved in industrial methylated spirit (65.6 ml) at 5°C and added
to base. The resulting slurry was then granulated, filtered and washed with 2
volumes the same solvent (65.6 ml). The damp solid was slurred at 5°C for 1
hr in 327.6 ml industrial methylated spirit, filtered, washed with 2 volumes of
the same solvent (65.6 ml) and dried under vacuum at 55°C for 24 hr. A yield
of besylate salt of amlodipine 65 g.
Brand name
Norvasc (Pfizer);Istin.
Therapeutic Function
Antianginal, Antihypertensive
General Description
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards. Amlodipine besylate is a calcium channel blocker, which inhibits the trans membrane influx of calcium ions into vascular smooth muscles and cardiac muscle. It belongs to the dihydropyridine family. It is used in combination with atorvastatin calcium to treat vasospastic angina, chronic stable angina, hypertension, in elevated serum triglyceride levels, primary dysbetalipoproteinemia.
Biological Activity
L-type calcium channel blocker that displays antihypertensive properties. Inhibits Ca 2+ -induced contractions in depolarized rat aorta (IC 50 = 1.9 nM) and displays vasoprotective effects in cardiovascular disease. Inhibits proliferation of human vascular smooth muscle cells and epidermoid carcinoma A431 cells (IC 50 = 25 μ M).
Biochem/physiol Actions
Amlodipine is an L-type calcium channel blocker. Amlodipine belongs to a class of cardiovascular drugs, which act at the voltage gated calcium channel of the CaV1, or L-type, class. Amlodipine also has antihypertensive and antianginal effects. Its activity resides mainly in the (-)-isomer. Amlodipine inhibits growth of human epidermoid carcinoma A431 cells and has antireproductive effects in male rats.
Veterinary Drugs and Treatments
Oral amlodipine appears to be a useful agent in the treatment of
hypertension in cats and many consider it the drug of choice for this
indication. In pharmacokinetic studies, amlodipine has decreased
blood pressure in dogs with chronic renal disease, but its efficacy in
treating
hypertensive dogs has been disappointing.
Hypertension in cats is usually secondary to other diseases (often
renal failure or cardiac causes such as thyrotoxic cardiomyopathy or
primary hypertrophic cardiomyopathy, etc.) and is most often seen
in middle-aged or geriatric cats. These animals often present with
acute clinical signs such as blindness, seizures, collapse or paresis. A
cat is generally considered hypertensive if systolic blood pressure is
>160 mmHg. Early reports indicate that if antihypertensive therapy
is begun acutely, some vision may be restored in about 50% of cases
of blindness secondary to hypertension.
references
[1] lee yj, park hh, koh sh, choi ny, lee ky. amlodipine besylate and amlodipine camsylate prevent cortical neuronal cell death induced by oxidative stress. j neurochem. 2011 dec;119(6):1262-70. doi: 10.1111/j.1471-4159.2011.07529.x. [2] yoshida j, ishibashi t, nishio m. antiproliferative effect of ca2+ channel blockers on human epidermoid carcinoma a431 cells. eur j pharmacol. 2003 jul 4;472(1-2):23-31. [3] henik ra, snyder ps, volk lm. treatment of systemic hypertension in cats with amlodipine besylate. j am anim hosp assoc. 1997 may-jun;33(3):226-34.
Check Digit Verification of cas no
The CAS Registry Mumber 111470-99-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,1,4,7 and 0 respectively; the second part has 2 digits, 9 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 111470-99:
(8*1)+(7*1)+(6*1)+(5*4)+(4*7)+(3*0)+(2*9)+(1*9)=96
96 % 10 = 6
So 111470-99-6 is a valid CAS Registry Number.
InChI:InChI=1/C20H25ClN2O5.CH4O3S/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21;1-5(2,3)4/h5-8,17,23H,4,9-11,22H2,1-3H3;1H3,(H,2,3,4)
111470-99-6Relevant articles and documents
A pharmaceutical model intermediate and its preparation method
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Paragraph 0038; 0047; 0053-0055; 0058, (2019/01/22)
The invention relates to a novel intermediate and its preparation method. The intermediate can be used for preparing amlodipine or pharmaceutically acceptable salts thereof; and amlodipine or salts thereof can be prepared through preparing the intermediate. The method is simple and safe to operate, avoids the use of flammable and explosive articles, and is in favor of the industrial mass production.
Method for preparing amlodipine besylate tablet by one-pot method
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Paragraph 0014, (2018/09/21)
The invention relates to a method for preparing an amlodipine besylate tablet by a one-pot method. The preparation method comprises the following steps: (1) taking phthaloyl amlodipine as a raw material, preparing an amlodipine solution in the presence of a solvent and a methylamine aqueous solution, wherein the reaction temperature is 10 to 50 DEG C, and the reaction time is 2 to 12 h; and (2) adding benzenesulfonic acid into the amlodipine solution in the step (1), stirring and mixing at 10 to 50 DEG C, and then separating to obtain the amlodipine besylate tablet. The method has the advantages that the amlodipine besylate tablet is prepared by the one-pot method, compared with the traditional preparation method of the amlodipine besylate tablet, the operation procedures are simple, a prepared amlodipine besylate tablet intermediate does not need to be separated, the loss of the amlodipine can be further reduced, the yield of the final amlodipine besylate tablet can be ensured, and the yield can be almost up to 100 percent; and meanwhile, by adopting the preparation method, impurities can be prevented from being introduced, the purity of the product can be improved, the purity can be up to 99.5 percent or above, the quality of the product is greatly ensured, and the industrial standard can be satisfied.
AN IMPROVED PROCESS FOR THE PREPARATION OF AMLODIPINE FREE BASE AND ACID ADDITION SALTS THEREOF
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Page/Page column 11-12, (2011/10/13)
Disclosed herein is an improved process for preparation of Amlodipine free base and acid addition salts thereof in good yield by deprotecting Phthaloyl Amlodipine using total concentration of 25% aqueous monomethyl amine in the reaction mixture and Amlodipine free base thus obtained is treated with suitable acids in aqueous medium to yield corresponding Amlodipine salts.
