Introduction：Basic information about Azelnidipine CAS 123524-52-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Azelnidipine Basic information
| Product Name: | Azelnidipine |
| Synonyms: | AZELNIDIPINE;3-[1-(Diphenylmethyl)-3-azetidinyl]-5-(1-methylethyl-2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate;AzelnidipineC33H34N406;AZELINIDIPINE;AZELNIDIPINE(FORR&DONLY);CS-905, RS-9054, 2-Amino-1,4-dihydro-6-methyl-4-(3 nitrophenyl)-3,5-pyridinedicarboxylic acid 3-[1-(diphenylmethyl)-3-azetidinyl] 5-(1-methylethyl) ester;Azelidipine;Azenildipine |
| CAS: | 123524-52-7 |
| MF: | C33H34N4O6 |
| MW: | 582.65 |
| EINECS: | 634-143-0 |
| Product Categories: | Inhibitors;Cardiovascular Drugs;API |
| Mol File: | 123524-52-7.mol |
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Azelnidipine Chemical Properties
| Melting point | 120-126°C |
| Boiling point | 709.3±60.0 °C(Predicted) |
| density | 1.33±0.1 g/cm3(Predicted) |
| storage temp. | Keep in dark place,Inert atmosphere,Room temperature |
| solubility | DMSO: >10mg/mL |
| pka | 7.89(at 25℃) |
| form | powder |
| color | Yellow |
| Merck | 14,907 |
| InChIKey | ZKFQEACEUNWPMT-UHFFFAOYSA-N |
| SMILES | C1(N)NC(C)=C(C(OC(C)C)=O)C(C2=CC=CC([N+]([O-])=O)=C2)C=1C(OC1CN(C(C2=CC=CC=C2)C2=CC=CC=C2)C1)=O |
| CAS DataBase Reference | 123524-52-7(CAS DataBase Reference) |
Safety Information
| Hazard Codes | Xn |
| Risk Statements | 22-41 |
| Safety Statements | 26-39 |
| WGK Germany | 3 |
| RTECS | US7968332 |
| HS Code | 2933.79.1500 |
| Toxicity | LD50 in female, male mice, female, male rats (mg/kg): 785, 979, 1267, 1971 orally |
Azelnidipine Usage And Synthesis
| Description | Azelnidipine, a member of the 1,4-dihydropyridine class of L-type calcium channelblockers with a slow onset profile, was marketed in Japan for the treatment ofhypertension. Azelnidipine is synthesized via the condensation of iso-propyl 2-(3-nitrobenzylidene)acetoacetate with (1-diphenylmethylazetidin-3-yl)-3,3-diamino acrylate.The diamino acrylate intermediate is prepared from the cyanoacetic ester by sequential treatment with HCl and ammonia. In receptor binding studies usingporcine heart membrane fractions, azelnidipine exhibits an IC50 of 3.1 nM and anapparent Ki of 2.1 nM. Its tight binding and slow onset are correlated with its highlipophilicity. A slow onset is also noted in vitro in a rat aortic strip contraction assay,and this effect continues after removal of the drug from the bath solution. In theconscious spontaneously hypertensive rat (SHR) model of hypertension, it was morepotent that nicardipine and also had a more gradual onset and long-lasting effect. Thiseffect was noted both when dosed orally or intravenously. When SHR dosed at 1 or3 mpk/day for 15 weeks, a sustained reduction in systolic blood pressure was noted (19and 43 mmHg reduction, respectively). Cardiac output was increased and totalperipheral resistance was decreased in each group. Clinical studies of patients withmild-to-moderate hypertension have shown that long-term treatment with azelnidipineprovided a sustained decrease in blood pressure (mean reduction systolic /diastolic:27.8/16.6 mmHg). It similarly controlled blood pressure, as did amlodipine at 24 h. Itpossesses a gradual onset of activity with plasma levels increasing before theantihypotensive effect is attained. After plasma levels drop, the pharmacodynamic effectis sustained. In clinical studies, azelnidipine did not show reflex tachycardia, a commonside effect of this class. Most common side effects were facial flushing and headache,similar to other dihydropyridines. Azelnidipine is dosed orally once daily (8–16 mg), israpidly absorbed in a dose-dependent fashion, and has a mean terminal half-life of19.2 h (8 mg dosage p.o. for seven days). Uniquely, it possesses a 2-amino functionassociated with a longer half-life than related agents wherein this moiety is a methyl.The very highly lipophilic 3-carboxylic ester side-chain is purported to contribute to thegradual onset of activity and prolonged pharmacodynamic effect, unlike other drugs inthis class. This compound exhibits a much less pronounced first-pass metabolic effectthan nicardipine. |
| Chemical Properties | Yellow Solid |
| Originator | Sankyo (Japan) |
| Uses | Azelnidipine is a dihydropyridine calcium channel blocker with antihypertensice activity. Azelnidipine is used for treating ischemic heart disease and cardiac remodeling after myocardial infarction. Studies show that Azelnidipine ttreatment can reduce the risk of hyperglycemia induced metabolic disorders |
| Definition | ChEBI: Azelnidipine is an isopropyl ester. |
| Application | Azelnidipine is a novel dihydropyridine derivative, a L-type calcium channel blocker, and an antihypertensive. Acute administration of azelnidipine prevents a sudden drop of cardiac function after acute stress. Azelnidipine may have a protective role in inflammation associated with atherosclerosis. |
| Brand name | Calblock |
| Biological Activity | Azelnidipine, a novel dihydropyridine derivative, is a L-type calcium channel blocker and antihypertensive. Unlike other L-type calcium channel blockers, azelnidipine causes minimal stimulation of the sympathetic nervous system despite its significant depressor effect. Azelnidipine may have a protective role in inflammation in atherosclerosis. |
| Synthesis | A solution of benzhydrylamine(46) and epichlorohydrin (47) was mixed without addingsolvent to give azetidinol 48 in 57% yield. DCCcoupling between cyanoacetic acid (49) and azetidinol 48 inhot THF gave ester 50 in 93% yield. Cyanoester 50 wastreated with ethanol and HCl gas in chloroform to giveimidate HCl salt 51, which was treated with ammonia gas inchloroform and ammonium acetate in acetonitrile to give thecorresponding amidinoacetate 52. A modified Hantzschreaction was employed to construct the 2-amino-1,4-dihydropyridine core structure. Compound 52 wascondensed with 2-(3-nitrobenzylidene)acetic acid isopropylester (55) in the presence of NaOMe in refluxing isopropanolto give the cyclized product, azelnidipine (V) in 74% yield.Benzylideneacetoacetate 55 was obtained through theKnoevenagel reaction employing 3-nitrobenzaldehyde (53)and isopropyl acetoacetate (54) in isopropanol containing acatalytic amount of piperidinium acetate at 45-55oC in 65%yield. |
Azelnidipine Preparation Products And Raw materials
| Raw materials | 2-Propenoic acid, 2-cyano-3-(3-nitrophenyl)--->Isopropyl 3-aminocrotonate-->Isopropyl 2-(3-nitrobenzylidene)acetoacetate-->3-Nitrobenzaldehyde-->Isopropyl acetoacetate |
