Azelnidipine

Yellow SolidAzelnidipine, a member of the 1,4-dihydropyridine class of L-type calcium channel blockers with a slow onset profile, was marketed in Japan for the treatment of hypertension. 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 usi

Azelnidipine is an isopropyl ester.|Azelnidipine is a dihydropyridine calcium channel blocker. It is marketed by Daiichi-Sankyo pharmaceuticals, Inc. in Japan. It has a gradual onset of action and produces a long-lasting decrease in blood pressure, with only a small increase in heart rate, unlike some other calcium channel blockers. It is currently being studied for post-ischemic stroke management.

1000 mL of a three-necked flask were added 50 g of amidin 4, 43.5 g of compound 5, 1000mL toluene and 7.7g sodium amide, mechanically stirred, heated to reflux, reaction 4 hours, TLC detection reaction is completed, cooled to room temperature crystallization.Filtration, solid non-drying directly into the mixed solution of toluene and n-hexane (1: 1.2-1.5)Warm to reflux and dissolve, naturally cool to 56 ° C, add seed, stop stirring, So that it naturally cool to 25 ° C, filter.The solid was purified again by the above method and dried at 40 ° C for 48 h under reduced pressure to give the α-crystalline azelnidipine 68.31 g, the yield was 90.01percent.
According to Japanese Examined Patent Publication (Kokoku) No. Hei 3-31715, sodium methoxide (0.27 g) was added to a solution of 2-(3-nitrobenzylidene)acetoacetic acid isopropyl ester (1.39 g) and amidinoacetic acid (1-benzhydryl-3-azetidinyl) ester acetate (1.62 g) in isopropyl alcohol (80 ml) and the mixture was heated under reflux for 4 hours. After the reaction mixture was cooled, superfluous material was removed and the solvent was evaporated under reduced pressure. The thus obtained residue was dissolved in ethyl acetate and the mixture was washed with water, followed by drying over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was subjected to silica gel column chromatography (toluene:ethyl acetate = 3:1) to obtain pale yellow 2-amino-1, 4-dihydro-6-methyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylic acid 3-(1-diphenylmethylazetidin-3-yl) ester 5-isopropyl ester (2.17 g, 74percent).Melting point: 95 - 98 C; IR spectrum (KBr, 'maxcm-1): 3450, 3310, 1675; Mass spectrum (CI, m/z) = 583 (M++1); 1H NMR (CDCl3) ' ppm: 1.08, 1.26 (6H, 2xd, J=6Hz), 2.35 (3H, s), 2.63, 3.06, 3.50, 3.62 (4H, 4xt, J=8Hz), 4.26 (1H, s), 4.9-5.0 (3H, m), 6.04 (1H, br.s), 6.11 (2H, br.s), 7.1-8.2 (14H, m).The reaction bottle was charged with 250 g of compound 3, 85 g of compound 4., 2.5 L of absolute ethanol, 50 g of sodium methoxide, and heating to reflux The reaction for 6 hours, after the reaction is finished, the solvent was evaporated under reduced pressure, the reaction bottle was charged with 2 L of ethyl acetate and 2 L of n-hexane, re-heating After dissolution, slowly cooling to 20 -30°c to crystallize for 2 h, filtered, drying to obtain a crude product of azelnidipine and 278 g, 78percent yield, 96percent purity.Refined A crude solution of 230 g of a bentonide was added to a mixed solution of 1.6 L of n-hexane and ethyl acetate (V: V = 1: 1). The temperature was gradually raised to dissolve the material. 11.5 g of activated charcoal was added and stirred for 0.5 h. And then slowly cooled to 0 ~ 10 ° C, filter cake, filter cake with 230ml ethyl acetate and n-hexane (V: V = 1: 1) leaching, drying 204.7g after the abundance of fine, Rate of 89percent, purity of 99percent

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

Molecular Weight:582.6
XLogP3:6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:9
Rotatable Bond Count:10
Exact Mass:582.24783482
Monoisotopic Mass:582.24783482
Topological Polar Surface Area:140
Heavy Atom Count:43
Complexity:1080
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes