39562-70-4Relevant articles and documents
Facile synthesis of 1,4-dihydropyridine monocarboxylic acids and unsymmetric dicarboxylates via quaternary ammonium salts of 2-aminoethyl 1,4-dihydropyridine-3,5-dicarboxylates
Kinugawa, Masahiko,Ogasa, Takehiro
, p. 3321 - 3331 (1997)
Useful 1,4-dihydropyridine unsymmetric dicarboxylates [nitrendipine (1), nicardipine (2)] and monocarboxylic acid 4 were prepared from unsymmetric 2-aminoethyl methyl 1,4-dihydropyridine-3,5-dicarboxylates 2 and 3 via their corresponding quaternary ammonium salts 5-9.
METHODS FOR TREATING CHRONIC FATIGUE SYNDROME AND MYALGIC ENCEPHALOMYELITIS
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, (2021/03/13)
In one aspect the invention relates to a method of treatment selected from the group consisting of: (a) treating a symptom such as pain in a subject identified or diagnosed as having Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); (b) treating a symptom such as pain in a subject having dysfunctional TRPM3 ion channel activity; (c) restoring NK cell function in a subject having dysfunctional TRPM3 ion channel activity; and (d) restoring calcium homeostasis in a subject having dysfunctional TRPM3 ion channel activity. The method comprises the step of administering to the subject a therapeutically effective amount of at least one therapeutic compound selected from the group consisting of: (i) an opioid receptor antagonist; (ii) an opioid antagonist; and (iii) a therapeutic compound that restores TRPM3 ion channel activity. In some embodiments the therapeutic compound is naltrexone hydrochloride.
Preparation method of nitrendipine
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Paragraph 0051-0071, (2020/05/14)
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of nitrendipine, which comprises the following steps: adding (E)-2-(3-nitrobenzylidene)-3-oxobutyrate and methyl 3-aminocrotonate into a first solvent, and carrying out a reflux reaction at a first temperature to obtain a first reaction solution; adding acetic anhydride into the first reaction solution at a second temperature to react to obtain a second reaction solution; carrying out a stirring reaction on the second reaction solution at a third temperature, and filtering to obtain a crude product of nitrendipine; and recrystallizing the crude product of nitrendipine to obtain nitrendipine. The invention provides a preparation method of nitrendipine, and aims to effectively controldimethyl ester impurities and diethyl ester impurities, improve the yield and shorten the reaction time so as to improve the productivity.
Preparation method of nitrendipine
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Paragraph 0042-0058, (2019/05/22)
The invention belongs to the field of drug synthesis, and particularly relates to a preparation method of nitrendipine. The preparation method is characterized by including following steps: (1), allowing 3-nitrobenzylidene ethyl acetoacetate intermediate and 3-aminomethyl crotonate according to a molar ratio of 1:1-1.1 to react at 70-75 DEG C in advance; (2), adding concentrated hydrochloric acidinto a reaction system of the step (1), and allowing reaction at 70-75 DEG C after adding is completed, wherein adding amount of the concentrated hydrochloric acid is 10-15% of molar weight of the 3-nitrobenzylidene ethyl acetoacetate intermediate; (3), cooling to 15-20 DEG C after reaction in the step (2) is completed, continuing reaction, and performing solid-liquid separation and recrystallization to obtain nitrendipine. Through process control, content of ester exchange impurities can be lowered effectively, and product yield can be increased.
Based on the three-step synthesis process of preparation of the nitrendipine (by machine translation)
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Paragraph 0020; 0025; 0031-0032; 0035-0036; 0041-0042, (2019/02/04)
The invention discloses a method based on three-step preparation of the nitrendipine synthesis process, comprising the following steps: S1 ammoniation reaction: liquid ammonia with methyl acetoacetate reflect the generated β - amino-crotonic acid methyl ester; S2 condensation reaction: will be m formaldehyde and acetyl ethyl acetate in the catalyst piperidine and glacial acetic acid under the action of the condensation reaction to obtain the pure 2 - (3 - nitryl asia phenmethyl) - acetyl ethyl acetate; S3 ring-closure reaction: the β - amino-crotonic acid methyl ester with 2 - (3 - nitryl asia phenmethyl) - acetyl ethyl acetate in the catalyst diisopropyl ethylamine/glacial acetic acid under the action of the Michael reaction, then molecule in cyclization to obtain nitrendipine; S4 refining, the invention - nitrobenzaldehyde between (SM1), acetyl ethyl acetate (SM2) and methyl acetoacetate (SM3) as the starting raw material preparation, heating the ring, three-step reaction qualified products can be obtained nitrendipine, not containing special reaction conditions. (by machine translation)
Synthesis, docking simulation, biological evaluations and 3D-QSAR study of 1,4-dihydropyridines as calcium channel blockers
El-Moselhy, Tarek Fathy,Sidhom, Peter Ayoub,Esmat, Eman Ahmed,El-Mahdy, Nageh Ahmed
, p. 893 - 903 (2018/10/31)
Resurgence to target L-type voltage-dependent calcium channels has been applied by the synthesis of two series of nifedipine analogues where the ortho- or a meta-nitrophenyl ring is retained. A pre-synthetic molecular docking study with a receptor model followed by molecular alignment has been performed on 47 compounds to predict the most active member. The IC50 values revealed that some of the compounds are similar to or more active than nifedipine. Substitution of groups at the 3- and 5-positions of the dihydropyridine (DHP) ring gave 3k, which is more active than nifedipine. Our valid three-dimensional quantitative structure–activity relationship (3D-QSAR) model prefigures the influence of lipophilicity, bulkiness and chelating effects of the C3 and C5 substituents. Bulky groups interfere with ring-to-ring hydrophobic interaction with tyrosine (Tyr)4311 and limit the efficiency of increasing the length of the hydrocarbon chain of esters at the 3- and 5-positions of the DHP ring as an approach to increasing the activity. The presence of a chelating substituent on the phenyl ring at the 4-position of the DHP ring ensures strong binding to the receptor and hence stabilization of the closed-channel conformation. The validation of 3D-QSAR model indicated its proficiency in predicting activity of newly compounds belonging to the same chemical class.
An efficient and recyclable 3D printed α-Al2O3 catalyst for the multicomponent assembly of bioactive heterocycles
Azuaje, Jhonny,Tubío, Carmen R.,Escalante, Luz,Gómez, Mónica,Guitián, Francisco,Coelho, Alberto,Caama?o, Olga,Gil, Alvaro,Sotelo, Eddy
, p. 203 - 210 (2016/12/09)
A catalytic methodology is reported that enables the efficient, operationally simple and environmentally friendly synthesis of diverse 1,4-dihydropyridines and 3,4-dihydropyrimidin-2(1H)-ones, including some relevant drugs and pharmacologically active derivatives. This strategy is based on the use of a 3D printed Al2O3 woodpile material that was sintered to generate a rigid structure with controlled porosity and noteworthy catalytic performance. The 3D printed Al2O3 catalyst exhibits remarkable efficacy as a Lewis acid in Biginelli and Hantzsch reactions and it can be recovered and reused ten times without any decrease in the activity. Remarkable E factors, excellent recyclability and scalability, broad substrate scope, short reaction times, excellent yields, solvent-free conditions and easy isolation procedures are key features of this methodology.
First Report About the Use of Micellar Keggin Heteropolyacids as Catalysts in the Green Multicomponent Synthesis of Nifedipine Derivatives
Palermo, Valeria,Sathicq, ángel G.,Constantieux, Thierry,Rodríguez, Jean,Vázquez, Patricia G.,Romanelli, Gustavo P.
, p. 1634 - 1647 (2016/08/30)
Abstract: Micellar Keggin heteropolyacid catalysts were prepared using hexadecyltrimethylammonium bromide (cetyltrimethylammonium bromide—CTAB), 1-hexadecyl-pyridinium chloride, and Keggin heteropolyacids H3PMo12O40 and H4PMo11VO40 as precursors. Four catalysts were prepared (PMo12C16, PMo11VC16, PMo12C16Py, and PMo11VC16Py) and characterized by 31P NMR, FT-IR, XRD, SEM analysis and textural properties (SBET). The acidic characteristics of the catalysts were determined by potentiometric titration with n-butylamine. A series of bioactive 1,4-dihydropyridine derivatives such as nifedipine and nemadipine B were synthesized using these new materials, in a one-pot procedure in ethanol. This methodology requires a reaction time of 8?h, and a temperature of 78?°C to obtain good to excellent yields of 1,4-dihydropyridine derivatives. The micellar Keggin catalysts are insoluble in polar media, which allows easy removal of the reaction products without affecting their catalytic activity. The leaching test showed that they have an excellent stability and can be used five times as heterogeneous catalysts without appreciable loss of the catalytic activity. Using the same material, unsymmetrical 1,4-dihydropyridines such as nitrendipine can be obtained through a sequence of steps in very good yield (78?%). Graphical Abstract: [Figure not available: see fulltext.]
Synthesis and antihypertensive activity evaluation in spontaneously hypertensive rats of nitrendipine analogues
Zhou, Kai,Wang, Xiao-Meng,Zhao, Yi-Zhi,Cao, Yong-Xiao,Fu, Qiang,Zhang, San-Qi
, p. 1325 - 1330 (2012/06/04)
The antihypertensive activity of nitrendipine analogues can be improved by properly lengthening its alkyl chain in 3- or 5-position. Nitrendipine and its seven analogues were synthesized, and their antihypertensive activities in spontaneously hypertensive rats (SHR) were evaluated by ig administration. It was found that 5-n-heptyl 3-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4- dihydropyridine- 3,5-dicarboxylate [(±)-5] exhibited the strongest antihypertensive effect amongst eight compounds. (?)-5-nheptyl 3-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine- 3,5-dicarboxylate [(+)-5] was also prepared. Antihypertensive activities of (±)-5 and (?)-5 in SHR were compared. The results showed that (±)-5 and (?)-5 had a higher potency than nitrendipine, and (+)-isomer was 1.79-fold the raceme at a dose of 2 mg/kg. Springer Science+Business Media, LLC 2010.
Catalytic effect of nanosized metal oxides on the Hantzsch reaction
Fedorova,Koryakova,Valova,Ovchinnikova,Titova,Rusinov,Charushin
experimental part, p. 566 - 572 (2011/01/07)
The effect of nanosized copper and aluminum oxides, which have a higher sorption capacity than that of bulk samples, on the Hantzsch reaction was studied. The adsorption of starting benzaldehydes and ethyl acetoacetate on the surface of copper and aluminum nanooxides resulted in the activation of these molecules and accelerated the Hantzsch reaction. In addition, considerable activation of ammonia and intermediates (chalcone and enamine) on the surface of aluminum nanooxide facilitated an increase in the rate and selectivity of the process. The experimental results were used to develop a one-pot method for the preparation of nifedipine and nitrendipine.
