39562-22-6Relevant articles and documents
Preparation method of cilnidipine
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Paragraph 0029; 0034; 0038; 0042, (2020/05/08)
The invention discloses a preparation method of high-purity cilnidipine. Methoxyethyl acetoacetate reacts with m-nitrobenzaldehyde to generate 2-(3-nitrobenzylidene) methoxyethyl acetoacetate, and the2-(3-nitrobenzylidene) methoxyethyl acetoacetate reacts with cinnamyl 3-aminocrotonate to generate cilnidipine. According to the method, the refining step of the 2-(3-nitrobenzylidene) methoxyethyl acetoacetate is added; the problem that impurities in the cilnidipine bulk drug are difficult to remove is solved, the subsequent refining process of the cilnidipine is simpler, and the purity of the finished product is high. The method has the advantages of simple synthesis process, complete reaction, high yield and low cost, and is very suitable for industrial production. .
Nimodipine impurity IV reference substance as well as preparation method and application thereof
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Paragraph 0055-0056, (2020/11/22)
The invention discloses a nimodipine impurity IV reference substance and a preparation method thereof. The method includes the steps that diketene, ethyl alcohol and triethylamine are taken and addedinto a container to be heated and cooled, reaction liquid is washed with water, washing liquid is discarded, anhydrous sodium sulfate is added and placed overnight, filtrate is obtained after filtration, ammonia gas is introduced into the filtrate until the filtrate is saturated, and the nimodipine impurity IV reference substance is obtained; and after the reaction is finished, m-nitrobenzaldehyde, methoxyethyl acetoacetate and ethanol are added, heating refulx is performed, the mixture is cooled and filtered, the solvent is removed through volatilization in a water bath to obtain a yellow viscous liquid, and recrystallization is carried out to obtain a yellow acicular crystal, namely the nimodipine impurity IV reference substance. The invention also discloses an application of the nimodipine impurity IV reference substance in nimodipine tablet consistency evaluation. According to the preparation method, the impurity IV can be prepared in a general analysis laboratory, special preparation equipment is not needed, the operation is simple, the purity of the obtained impurity reference substance can reach 98.4%, the purity requirement of the reference substance is met, and the preparation method can be used for consistency evaluation of the variety.
Design and synthesis of 4-alkyl-2-amino(acetamino)-6-aryl-1,3-thiazine derivatives as influenza neuraminidase inhibitors
Li, Wan,Xia, Lin,Hu, Aixi,Liu, Ailin,Peng, Junmei,Tan, Weiqing
, p. 635 - 644 (2013/09/24)
With a convenient and economical method, two series of 1,3-thiazine derivatives 1 and 2 were synthesized, and their neuraminidase (NA) inhibitory activities were evaluated. The pharmacological results showed that most of the compounds have potent NA inhibitory activity. Especially, 1g exhibited the best activity against influenza virus A (H1N1) NA (IC50 = 29.06 μg/mL), and its crystal structure was determined by single-crystal X-ray diffraction. The preliminary biological assay indicated that 1,3-thiazine could be used as a core structure to design novel influenza NA inhibitors. Two series of novel 1,3-thiazine analogs were synthesized and their neuraminidase (NA) inhibitory activities were evaluated. Most of the compounds have potent NA inhibitory activity. Compound 1g exhibited the best activity against influenza virus A (H1N1) NA with an IC50 of 29.06 μg/mL, and its crystal structure was determined by single-crystal X-ray diffraction.
Dimethylamine benzoate or p-anisate catalysed process for the preparation of 4-(nitrophenyl)-dihydropyridines
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, (2008/06/13)
PCT No. PCT/EP96/01090 Sec. 371 Date Aug. 18, 1997 Sec. 102(e) Date Aug. 18, 1997 PCT Filed Mar. 14, 1996 PCT Pub. No. WO96/29310 PCT Pub. Date Sep. 26, 1996A method for the preparation of 4-(nitrophenyl)-dihydro-pyridines by reacting a benzaldehyde with an acetoacetate and reacting the resulting benzylidene derivative with an enamine derivative. Both reactions are catalyzed by dimethylamine benzoate or p-anisate.
Novel 2-amino-1,4-dihydropyridine calcium antagonists. II. Synthesis and antihypertensive effects of 2-amino-1,4-dihydropyridine derivatives having N,N-dialkylaminoalkoxycarbonyl groups at 3- and/or 5-positions
Kobayashi,Inoue,Nishino,Fujihara,Oizumi,Kimura
, p. 797 - 817 (2007/10/02)
Novel 2-amino-1,4-dihydropyridine derivatives I, which contain N,N-dialkylaminoalkoxycarbonyl groups at the 3- and/or 5-position, were synthesized and their antihypertensive effects were evaluated in spontaneously hypertensive rats. Remarkably prolonged duration of antihypertensive action was observed when a tertiary amino group was introduced into either the 3- or 5-ester side-chain of the 1,4-dihydropyridine ring. In particular, the compounds containing cyclic amino moieties at the 3-position showed greater potency than those with acyclic amino moieties. Chemical modification studies indicated that the two ester side-chains of 1,4-dihydropyridine at the 3- and 5-position might function in a different manner in relation to the antihypertensive activities. 3-(1-Benzhydrylazetidin-3-yl) 5-isopropyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxyl ate, I-43 (CS-905), exhibited potent and long-lasting antihypertensive effects with gradual onset of action, and is a promising candidate as an antihypertensive drug.
Synthesis and antihypertensive activities of new 1,4-dihydropyridine derivatives containing a nitrooxy moiety at the 3-ester position
Ogawa,Nakato,Tsuchida,Hatayama
, p. 108 - 116 (2007/10/02)
The synthesis of a new series of dihydropyridines containing a nitrooxy moiety at the 3-ester position is described. The antihypertensive activity of the compounds was examined and compared with that of nifedipine; some of them were relatively potent. The structure-activity relationship is also discussed.
Process for the preparation of 1,4-dihydropyridinedicarboxylic esters
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, (2008/06/13)
In the preparation of a 1,4-dihydropyridine of the formula STR1 in which R is a phenyl radical which is optionally substituted once or twice by nitro and/or chlorine, R1 is a C1 -C4 -alkyl radical which is optionally substituted by a C1 -C4 -alkoxy group, and R2 is a C1 -C12 -alkyl radical which is optionally substituted by a C1 -C4 -alkoxy group, a trifluoromethyl group or the radical (C6 H5 CH2) (CH3)N, by preparing an ylidene compound of the formula STR2 and reacting such ylidene compound with an enamine compound of the formula STR3 the improvement which comprises preparing the ylidene compound by reaction of a ketocarboxylic ester of the formula STR4 with an aldehyde of the formula RCHO, in a solvent in the presence of a catalytic amount of any acetate salt of an amine, at a temperature from about -10° C. up to 100° C. The products symmetrical or unsymmetrical, are produced in high yield and purity.
Nimodipine: Synthesis and metabolic pathway
Meyer,Wehinger,Bossert,Scherling
, p. 106 - 112 (2007/10/02)
Key step of the synthesis of the calcium antagonistic cerebral vasodilator (±) isopropyl-2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (Bay e 9736, nimodipine) is the cyclising Michael addition. A pharmacokinetic study with 14C-nimodipine in the rat revealed as major metabolites the dihydropyridines as well as the pyridines. A potential metabolic pathway is discussed involving ether cleavage and oxidation to the pyridine form as primary biotransformation steps. Reference metabolites were synthesized using 1,4-dihydropyridines with appropriate functionalities as precursors.
