- Preparation method of manidipine hydrochloride
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The invention discloses a preparation method of manidipine hydrochloride and belongs to the technical field of medicine preparation. Piperazine serving as a starting raw material is used for synthesis of N-(2-hydroxyethyl)piperazine, then 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine is synthesized, and 2-(4-diphenylmethyl-1-piperazinyl)ethyl acetoacetic ester is synthesized; 2-(4-diphenylmethyl-1-piperazinyl)ethyl acetoacetic ester, m-nitrobenzaldehyde and methyl 3-aminocrotonate are dissolved in isopropanol, the mixture is subjected to heating reflux, a solvent is removed through steaming, residues are dissolved in trichloromethane, the mixture is dried with anhydrous sodium sulfate and filtered, a solvent of the filtrate is recovered under reduced pressure, residues are mixed with methanol to be completely dissolved, hydrogen chloride is introduced in an ice bath, the solvent is removed through steaming, residues are mixed with methanol, activated carbon is added for decoloration, filtering is performed, filtrate is cooled, and manidipine hydrochloride is obtained. The preparation method of manidipine hydrochloride is simple in process, the yield is high, the cost is low, and the product purity is high.
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Paragraph 0039; 0040; 0047; 0057; 0067
(2017/12/06)
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- 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
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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.
- Kobayashi,Inoue,Nishino,Fujihara,Oizumi,Kimura
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p. 797 - 817
(2007/10/02)
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- Substituted heterocyclylalkyl esters of 1,4-dihydropyridine-3,5-dicarboxylic acids
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Dihydropyridine derivatives and acid addition salts thereof which are of use as prophylactic or/and therapeutic drugs for cardiovascular diseases, said dihydropyridine derivatives having the formula STR1 wherein R1, R2 and R3 are the same or different and each is alkyl, cycloalkyl, cycloalkylalkyl or alkoxyalkyl; R4 and R5 are the same or different and each is hydrogen, halogen, nitro, trifluoromethyl, alkyl, cycloalkyl, alkoxy, cyano, alkoxycarbonyl or alkylthio; R6 is hydrogen, alkyl, cycloalkyl, aralkyl, aryl or a pyridyl; X is oxygen, sulfur, vinylene, azomethine or a group of the formula STR2 A is alkylene; Ar is aryl or a pyridyl; m is an integer of 1 to 3; n is an integer of 0 to 2.
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- Substituted piperazinyl alkyl esters of 2-amino-4-aryl-1,4-dihydro-6-alkyl-3,5-pyridinedicarboxylates
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Dihydropyridine derivatives and acid addition salts thereof which are of use as prophylactic or/and therapeutic drugs for cardiovascular diseases, said dihydropyridine derivatives having the formula STR1 wherein R1 is a hydrogen atom or an aryl, R2 and R3 are the same or different and each is an aryl, R4 and R6 are the same or different and each is a lower alkyl, R5 is amino or a lower alkyl, A is an alkylene, X is N or CH and m and n are the same or different and each is 0 or 1, with the proviso that when X is N, R5 is amino.
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