14205-39-1Relevant articles and documents
Highly enantioselective rhodium-catalyzed hydrogenation of β-dehydroamino acid derivatives using monodentate phosphoramidites
Pena, Diego,Minnaard, Adriaan J.,De Vries, Johannes G.,Feringa, Ben L.
, p. 14552 - 14553 (2002)
New and very easily accessible monodentate phosphoramidite ligands have been developed that lead to excellent ee's and full conversions in the hydrogenation of (E)- and (Z)-β-dehydroamino acid derivatives with both aliphatic and aromatic side chains. Particularly, two different catalytic systems were established for (E)-β-(acylamino)acrylates (98-99% ee) and (Z)-β-(acylamino)acrylates (92-95% ee) based on phosphoramidites 2 and 3, respectively. Copyright
Synthesis and structural study of new highly lipophilic 1,4-dihydropyridines
Suarez, Margarita,De Armas, Merly,Ramirez, Oney,Alvarez, Amaury,Martinez-Alvarez, Roberto,Molero, Dolores,Seoane, Carlos,Liz, Ramon,De Armas, Hector Novoa,Blaton, Norbert M.,Peeters, Oswald M.,Martin, Nazario
, p. 1567 - 1576 (2005)
A new series of 1,4-dihydropyridines (1,4-DHPs) endowed with ester groups bearing long and functionalised alkoxy chains at the C3 and C5 positions of the nitrogen ring have been prepared from the corresponding β-keto esters which were in turn prepared by a lipase catalysed transesterification reaction. The structural study has been carried out by X-ray crystallography and theoretical calculations at the semiempirical (AM1), ab initio (HF/6-31G*) and B3LYP/6-31G* levels and reveals that the long alkyl chains do not have any influence on the required geometry of the 1,4-DHPs for biological activity. However, these chains have a strong impact on the lipophilicity and, therefore, they could be used to gain a better control of the duration of the pharmacological action. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.
Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells
Shekari, Farnaz,Sadeghpour, Hossein,Javidnia, Katayoun,Saso, Luciano,Nazari, Farhad,Firuzi, Omidreza,Miri, Ramin
, p. 233 - 244 (2015)
Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure-activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin's IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5-25 μM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77-15.60 μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents.
Hantzsch synthesis of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o- methoxyphenyl)-1,4-dihydropyridine; a novel cyclisation leading to an unusual formation of 1-amino-2-methoxycarbonyl-3,5-bis(o-methoxyphenyl)-4-oxa- cyclohexan-1-ene
Filipan-Litvic, Mirela,Litvic, Mladen,Cepanec, Ivica,Vinkovic, Vladimir
, p. 2546 - 2558 (2007)
Hantzsch condensation of two equivalents of methyl-3-aminocrotonate with (m- and p)-methoxybenzaldehyde afforded the expected products 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-methoxyphenyl)-1,4-dihydropyridine and 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(p-methoxyphenyl)-1,4-dihydropyridine, whereas o-methoxybenzaldehyde produced mainly 1-amino-2-methoxycarbonyl-3,5- bis(o-methoxy-phenyl)-4-oxa-cyclohexan-1-ene. The structure of the product, not previously reported in the literature, was determined by 1D and 2D NMR spectra and its MS fragmentation. This is the first example of cyclisation leading to a substituted pyran rather than 1,4-DHP under typical Hantzsch reaction conditions. A plausible mechanism for its formation is postulated.
Reversal of multidrug resistance in cancer cells by novel asymmetrical 1,4-dihydropyridines
Firuzi, Omidreza,Javidnia, Katayoun,Mansourabadi, Elham,Saso, Luciano,Mehdipour, Ahmad Reza,Miri, Ramin
, p. 1392 - 1402 (2013)
Multidrug resistance (MDR) is an important obstacle that limits the efficacy of chemotherapy in many types of cancer. In this study, 14 novel asymmetrical DHPs possessing pyridyl alkyl carboxylate substitutions at C 3 and alkyl carboxylate groups at C5 in addition to a nitroimidazole or nitrophenyl moiety at C4 position were synthesized. Calcium channel blocking (CCB) activity was measured in guinea pig ileal longitudinal smooth muscle. Cytotoxicity was tested on 4 human cancer cell lines, while MDR reversal capacity was examined on P-glycoprotein overexpressing doxorubicin resistant MES-SA-DX5 and compared with non-resistant MES-SA cells. Compounds showed different CCB (IC50: 29.3 nM-4.75 μM) and cytotoxic activities (IC50: 6.4 to more than 100 μM). Several compounds having nitrophenyl moiety at C4, could significantly reverse resistance to doxorubicin at 0.5 and 1 μM. The most active ones were 7e and 7g containing ethyl carboxylate and isopropyl carboxylate at C 5, respectively. CCB activity, which is considered an undesirable effect for these agents, of 7e and 7g were 33 and 20 times lower than nifedipine, respectively. In conclusion, the newly synthesized asymmetrical DHP compounds showed promising MDR reversal and antitumoral activities with low CCB effects and could be of therapeutic value in drug resistant cancer.
Synthesis and Biological Activities of Nicotinaldehyde Based 1,4-Dihydropyridinedicarboxylates
Hariprasad, K. S.,Prakasham, R. S.,Praveena, G.,Raju, B. China,Ramya, S.,Suchitra Rani, K.,Tiwari, A. K.,Zehra, A.
, p. 1335 - 1340 (2021/12/23)
Abstract: 1,4-Dihydropyridinecarboxylates were prepared by the reaction of nicotinaldehydes with aminocrotonoates in the presence of p-TsOH at room temperature. The prepared compounds were evaluated for their anti-microbial, free-radical scavenging and α-glucosidase inhibitory activities. Compounds diethyl 2,6-diphenyl-4-(pyridin-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate and diethyl 4-(2-chloro-5-(4-fluorophenyl)pyridin-3-yl)-2,6-diphenyl-1,4-dihydropyridine-3,5-dicarboxylate were identified as potent anti-fungal agents. The compounds diethyl 2,6-dimethyl-4-(pyridin-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate, dimethyl 4-(2-chloropyridin-3-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate and diethyl 2,6-dimethyl-4-(pyridin-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate were identified as ABT?+ free radical scavengers. The compounds diethyl 4-(2-chloro-5-phenylpyridin-3-yl)-2,6-diphenyl-1,4-dihydropyridine-3,5-dicarboxylate and diethyl 4-(2-chloro-5-phenylpyridin-3-yl)-2,6-diphenyl-1,4-dihydropyridine-3,5-dicarboxylate denoted α-glucosidase inhibitory activity.
Based on the three-step synthesis process of preparation of the nitrendipine (by machine translation)
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Paragraph 0020-0021; 0031-0033; 0039; 0045; 0051, (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)
Unsymmetric dihydropyridines bearing 2-pyridyl methyl carboxylate as modulators of P-glycoprotein; Synthesis and biological evaluation in resistant and non-resistant cancer cells
Nejati, Maryam,Sadeghpour, Hossein,Ranjbar, Sara,Javidnia, Katayoun,Edraki, Najmeh,Saso, Luciano,Firuzi, Omidreza,Miri, Ramin
, p. 603 - 614 (2019/08/06)
Multi-drug resistance (MDR) in cancer cells is often associated with overexpression of P-glycoprotein (P-gp or ABCB1 or MDR1); therefore, modulators of this transporter might be helpful in overcoming MDR. In this study, 16 novel unsymmetrical dihydropyridine (DHP) derivatives bearing 2-pyridyl methyl carboxylate at C3 and a nitroimidazole or nitrophenyl ring at C4 positions of the DHP ring were synthesized. Their cytotoxicity was tested against four human cancer cells by MTT assay. The reversal capacity of MDR was examined in P-gp overexpressing cells (MES-SA/DX5) by measuring the alteration of doxorubicin's IC50 and performing flow cytometric determination of intracellular rhodamine 123 accumulation. The calcium channel blocking (CCB) activity, as a side effect of DHPs, was tested on the ileum of a guinea pig. Molecular docking was performed to explain the binding mode of compounds. Two derivatives, 4a and 4c, containing 4-nitrophenyl at C4 and possessing methyl (4a) and iso-propyl (4c) carboxylates at the C5 position of DHP core demonstrated superior cytotoxic and MDR reversal activities and lower CCB effect. Docking analysis confirmed the importance of the 4-nitrophenyl ring for P-gp inhibitory activity. Some of the synthesized DHP derivatives with considerable MDR reversal capacity could be promising compounds for further discovery of useful agents for management of drug resistant cancer.
A new process for the preparation of felodipine (by machine translation)
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Paragraph 0024; 0026; 0027, (2018/07/06)
The invention discloses a new process for the preparation of felodipine, including: 1) to acetyl acetic acid methyl ester as the raw material, to prepare the 3 - amino-crotonic acid methyl ester; 2) to 2, 3 - dichloro formaldehyde and acetyl acetic acid ethyl ester as the raw material, to prepare the 2, 3 - two chlorine asia phenmethyl acetyl ethyl acetate; 3) to 2, 3 - two chlorine asia phenmethyl acetyl ethyl acetate, 3 - amino-crotonic acid methyl ester as the raw material, prepare the felodipine. The invention of the preparation process of felodipine, intermediates for the preparation of 3 - amino-crotonic acid methyl ester having a melting point of 83 - 35 °C, far higher than the widely used of the intermediate 3 - amino-crotonic acid ethyl ester (33 - 35 °C), therefore the stability can be improved, convenient in a wider temperature conditions production and storage, is more favorable to the industrialized production and application. At the same time, the process high product yield, high purity, step is simple, easy to operate, and has good practicability. (by machine translation)
Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination
Sun, Jiyun,Zhen, Xiaohua,Ge, Huaibin,Zhang, Guangtao,An, Xuechan,Du, Yunfei
supporting information, p. 1452 - 1458 (2018/07/05)
The reaction of enamine compounds with the Togni reagent in the presence of CuI afforded β-trifluoromethylated enamine intermediates, which were converted directly to biologically interesting trifluoromethylated 2H-azirines by an iodosobenzene (PhIO)-mediated intramolecular azirination in a one-pot process.
