- Highly enantioselective rhodium-catalyzed hydrogenation of β-dehydroamino acid derivatives using monodentate phosphoramidites
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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
- Pena, Diego,Minnaard, Adriaan J.,De Vries, Johannes G.,Feringa, Ben L.
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- Synthesis and structural study of new highly lipophilic 1,4-dihydropyridines
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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.
- 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
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- Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells
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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.
- Shekari, Farnaz,Sadeghpour, Hossein,Javidnia, Katayoun,Saso, Luciano,Nazari, Farhad,Firuzi, Omidreza,Miri, Ramin
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- 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
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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.
- Filipan-Litvic, Mirela,Litvic, Mladen,Cepanec, Ivica,Vinkovic, Vladimir
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- Reversal of multidrug resistance in cancer cells by novel asymmetrical 1,4-dihydropyridines
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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.
- Firuzi, Omidreza,Javidnia, Katayoun,Mansourabadi, Elham,Saso, Luciano,Mehdipour, Ahmad Reza,Miri, Ramin
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- Synthesis and Biological Activities of Nicotinaldehyde Based 1,4-Dihydropyridinedicarboxylates
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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.
- Hariprasad, K. S.,Prakasham, R. S.,Praveena, G.,Raju, B. China,Ramya, S.,Suchitra Rani, K.,Tiwari, A. K.,Zehra, A.
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p. 1335 - 1340
(2021/12/23)
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- Based on the three-step synthesis process of preparation of the nitrendipine (by machine translation)
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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)
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Paragraph 0020-0021; 0031-0033; 0039; 0045; 0051
(2019/02/04)
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- Unsymmetric dihydropyridines bearing 2-pyridyl methyl carboxylate as modulators of P-glycoprotein; Synthesis and biological evaluation in resistant and non-resistant cancer cells
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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.
- Nejati, Maryam,Sadeghpour, Hossein,Ranjbar, Sara,Javidnia, Katayoun,Edraki, Najmeh,Saso, Luciano,Firuzi, Omidreza,Miri, Ramin
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p. 603 - 614
(2019/08/06)
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- A new process for the preparation of felodipine (by machine translation)
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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)
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Paragraph 0024; 0026; 0027
(2018/07/06)
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- Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination
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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.
- Sun, Jiyun,Zhen, Xiaohua,Ge, Huaibin,Zhang, Guangtao,An, Xuechan,Du, Yunfei
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supporting information
p. 1452 - 1458
(2018/07/05)
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- Oxidative Coupling of Enamines and Disulfides via Tetrabutylammonium Iodide/tert-Butyl Hydroperoxide-Mediated Intermolecular Oxidative C(sp2) S Bond Formation Under Transition Metal-Free Conditions
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The reaction of enamine compounds with disulfides in the presence of tert-butyl hydroperoxide and a catalytic amount of tetrabutylammonium iodide conveniently afforded a variety of α-thioenamine compounds through the intermolecular oxidative C(sp2) S coupling. Incorporating both of the sulfide moieties in the disulfides into the final products under oxidative conditions, this novel approach exhibits the feature of atom efficiency. A radical mechanistic pathway for the reaction process has been proposed. (Figure presented.) .
- Sun, Jiyun,Zhang-Negrerie, Daisy,Du, Yunfei
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supporting information
p. 2035 - 2040
(2016/07/16)
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- Facile synthesis of pyrido[2,3-d]pyrimidines via cyclocondensation of 4,6-dichloro-2-methylsulfanylpyrimidine-5-carbaldehyde with β-substituted β-aminoacrylic esters
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Abstract A new facile synthesis of pyrido[2,3-d]pyrimidin-4-ones via cyclocondensation of 4,6-dichloro-2-methylsulfanylpyrimidine-5-carbaldehyde with β-alkyl and β-aryl-β-aminoacrylic esters followed by hydrolysis of chlorine atom at position 4 of pyridopyrimidine ring has been developed. The cyclocondensation was found to be accelerated by acid.
- Chizhova, Maria E.,Bakulina, Olga Yu.,Ivanov, Alexander Yu.,Lobanov, Pavel S.,Dar'in, Dmitrii V.
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supporting information
p. 6196 - 6203
(2015/08/03)
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- Multicomponent diversity-oriented synthesis of symmetrical and unsymmetrical 1,4-dihydropyridines in recyclable glycine nitrate (GlyNO 3) ionic liquid: A mechanistic insight using Q-TOF, ESI-MS/MS
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Multicomponent reactions are compelling strategies for generating a chemically diverse set of multifunctionalized heterocyclic motifs with high atom economy, rendering the transformations green. These strategies can further become more prolific if catalyst recyclability, compatibility and exploration of precise mechanistic pathways are considered. To this end, an inexpensive and recyclable glycine nitrate (GlyNO3) ionic liquid has been efficiently employed to obtain diversely substituted symmetrical and unsymmetrical 1,4-dihydropyridines with up to 93% yields via three and four components, respectively. The catalyst recyclability and compatibility to obtain both symmetrical and unsymmetrical 1,4 DHPs under identical reaction conditions are added benefits to its practical utility. Furthermore, progress of the reaction was monitored by Q-TOF, direct infusion electrospray ionization mass spectrometry (ESI-MS), and key cationic intermediates involved in the reaction have been further identified by a tandem MS experiment (Q-TOF, ESI-MS/MS), which served as the proof of concept to the mechanistic model. This is the first report which revealed that the Hantzsch reaction predominantly follows the diketone pathway among four competing reaction pathways. the Partner Organisations 2014.
- Kumar, Rajesh,Andhare, Nitin H.,Shard, Amit,Richa,Sinha, Arun Kumar
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p. 19111 - 19121
(2014/05/20)
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- Direct oxidative coupling of enamines and electron-deficient amines: TBAI/TBHP-mediated synthesis of substituted diaminoalkenes under metal-free conditions
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A metal-free cross-coupling of enamines and electron-de fi cient amines through oxidative C(sp2)-N bond formation has been realized by using TBAI as catalyst and TBHP as oxidant. This novel strategy allows for an efficient organocatalytic synthesis of the synthetically useful diaminoalkene derivatives and is highlighted by appealing features such as readily available of the starting materials, wide substrate scope and transition-metal-free characteristics. (Chemical Equation Presented).
- Yuan, Yucheng,Hou, Wenjuan,Zhang-Negrerie, Daisy,Zhao, Kang,Du, Yunfei
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supporting information
p. 5410 - 5413
(2015/01/09)
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- Rhodium-catalyzed enantioseletive hydrogenation of tetrasubstituted α-acetoxy β-enamido esters: A new approach to chiral α-hydroxyl-β-amino acid derivatives
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Asymmetric hydrogenation of tetrasubtitued α-acetoxy β-enamido esters with rhodium catalysts based on chiral diphosphine ligands provides an efficient and concise route to the synthesis of chiral α-hydroxyl-β-amino acid derivatives in excellent enantioselectivities. The products are valuable chiral building blocks in many biologically active compounds and have important applications in organic synthesis.
- Wang, Qingli,Huang, Wenhua,Yuan, Haoquan,Cai, Qin,Chen, Liming,Lv, Hui,Zhang, Xumu
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supporting information
p. 16120 - 16123
(2015/02/18)
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- Total synthesis of (-)-kopsinine by an asymmetric one-pot [N+2+3] cyclization
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All together now: A common intermediate of Kopsia alkaloids was synthesized from cis-2,3-disubstituted piperidine, which was obtained with 98 % ee in 85 % yield using chiral diether-controlled asymmetric conjugate addition of lithium amide to indolepropenoate, followed by C,N dual alkylation with 1-chloro-3-iodopropane. The synthesis of (-)-kopsinine was accomplished via the intermediate in 9.0 % overall yield in 13 steps. Copyright
- Yamamoto, Yasutomo,Tomioka, Kiyoshi,Harada, Shingo,Sakai, Takeo,Takasu, Kiyosei,Yamada, Ken-Ichi
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supporting information
p. 2196 - 2198,3
(2020/08/24)
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- Cu(OAc)2/TFA-promoted formal [3 + 3] cycloaddition/oxidation of enamines and enones for synthesis of multisubstituted aromatic amines
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New strategies for the oxidative cycloaddition of enones with enamines are developed. These cycloaddition reactions directly afford substituted aromatic amines, which are important in organic chemistry, in moderate to good yield. Cu(OAc)2/TFA is shown to be essential to achieve high reaction efficiency.
- Li, Liang,Zhao, Mi-Na,Ren, Zhi-Hui,Li, Jian-Li,Guan, Zheng-Hui
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supporting information; experimental part
p. 3506 - 3509
(2012/08/08)
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- PROCESS FOR CONTINUOUS FLOW SYNTHESIS OF β-ΑΜΙΝΟ CROTONATE
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Beta aminocrotonates are important intermediates for the synthesis of Ca channel blockers. The processes available in the art are batch processes with yields about 85%. There are no continuous processes available for the synthesis of such compounds. This gap in the art is addressed by the invention by disclosing a continuous process resulting in high yields of beta amino crotonates.
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Page/Page column 6-7
(2012/11/13)
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- Direct β-acyloxylation of enamines via PhIO-mediated intermolecular oxidative C-O bond formation and its application to the synthesis of oxazoles
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A direct β-acyloxylation of enamine compounds has been achieved by using iodosobenzene (PhIO) as an oxidant to realize the intermolecular oxidative C(sp2)-O bond formation between enamines and various carboxylic acids, including N-protected amino acids. The transformation tolerates a wide range of functional groups and furnishes a variety of β-acyloxy enamines that can be conveniently converted to oxazole compounds via cyclodehydration.
- Liu, Xin,Cheng, Ran,Zhao, Feifei,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
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supporting information
p. 5480 - 5483,4
(2012/12/12)
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- Direct β-acyloxylation of enamines via PhIO-mediated intermolecular oxidative C-O bond formation and its application to the synthesis of oxazoles
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A direct β-acyloxylation of enamine compounds has been achieved by using iodosobenzene (PhIO) as an oxidant to realize the intermolecular oxidative C(sp2)-O bond formation between enamines and various carboxylic acids, including N-protected amino acids. The transformation tolerates a wide range of functional groups and furnishes a variety of β-acyloxy enamines that can be conveniently converted to oxazole compounds via cyclodehydration.
- Liu, Xin,Cheng, Ran,Zhao, Feifei,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
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supporting information
p. 5480 - 5483
(2013/01/15)
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- Synthesis of unsymmetrical 1, 4-dihydropyridine derivatives in ionic liquid and inference on the formation mechanism of furopyridines
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Aromatic aldehydes, methyl acetoacetate, ethyl acetoacetate, ammonium acetate, ethyl 4-chloroacetoacetate as materials, eight unsymmetrical 1, 4-dihydropyridine derivatives were synthesized in ionic liquid [Bmim]OH in short time with the 60%-90% yield, and the ionic liquid could be utilized for 5 times repeatedly with the no decrease of the yield, four of products [3(a-d)] (see in Table-1) were synthesized through Knoevenagel and Michael addition reaction, and another four Furopyridines [3(e-h)] (see in Table-2) through one-pot synthesis whose formation mechanism being different from that of [3(a-d)] was first inferred.
- Zhang, Jian,Jin, Long Fei
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experimental part
p. 916 - 921
(2012/02/16)
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- Solvent-free synthesis of functionalized pyridine derivatives using Wells-Dawson heteropolyacid as catalyst
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Wells-Dawson heteropolyacids (H6P2W 18O62·24H2O) were used as catalysts in the Hantzsch-like multicomponent condensation reaction with 3-formylchromones as aldehyde component, a β-ketoester and ammonium acetate, under solvent-free conditions at 80 °C. Although the desired products were obtained, functionalized pyridines were the main reaction product and became the alternative route to dihydropyridine ring formation. Based on the proposed mechanisms for the formation of each of the obtained products, the multicomponent reaction was modified to afford only the functionalized pyridines (60-99%). Our procedure represents a clean alternative for the synthesis of several highly functionalized pyridines.
- Sanchez, Laura M.,Sathicq, Angel G.,Jios, Jorge L.,Baronetti, Graciela T.,Thomas, Horacio J.,Romanelli, Gustavo P.
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scheme or table
p. 4412 - 4416
(2011/09/19)
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- Synthesis of β-amino acid derivatives via copper-catalyzed asymmetric 1,4-reduction of β-(acylamino)acrylates
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A new set of reaction conditions has been established to facilitate the copper-catalyzed enantioselective 1,4-reduction of β-(acylamino)acrylates toward a selection of β-alkyl-β-amino acid derivatives in high yields and with uniformly high ee values (up to 99%) irrespective of the use of (E)- or (Z)-substrates.
- Wu, Yan,Qi, Shan-Bin,Wu, Fei-Fei,Zhang, Xi-Chang,Li, Min,Wu, Jing,Chan, Albert S. C.
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supporting information; experimental part
p. 1754 - 1757
(2011/05/12)
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- Pyrrole synthesis via allylic sp3 C-H activation of enamines followed by intermolecular coupling with unactivated alkynes
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A conceptually novel pyrrole synthesis is reported, efficiently merging enamines and (unactivated) alkynes under oxidative conditions. In an intermolecular Rh catalyzed process, the challenging allylic sp3 C-H activation of the enamine substrates is followed by the cyclization with the alkyne (R3 = CO2R). Alternatively, in some cases (R 3 = CN), the enamine can be utilized for a vinylic sp2 C-H activation. A total of 17 examples with yields above 60% is presented, together with the results of an initial mechanistic investigation.
- Rakshit, Souvik,Patureau, Frederic W.,Glorius, Frank
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supporting information; experimental part
p. 9585 - 9587
(2010/09/10)
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- Synthesis and biological evaluation of some new 1,4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents
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Tuberculosis is a leading infectious cause of death worldwide. Because of the concern of the resistance to most of the commonly used drugs displayed by the considered mycobacteria, most efforts have been done to introduce new anti-tubercular agents. Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant anti-tubercular activity. In this study, we synthesized new derivatives of 1,4-dihydropyridines in which different alkyl and aryl esters and diethyl carbamoyl are substituted in C-3 and C-5 of the DHP ring. In addition nitroimidazole ring is substitutes at C-4 position. These asymmetric analogues were synthesized by a modified Hantzsh reaction using procedure reported by Meyer. The in vitro anti-tubercular activity of compounds against Mycobacterium tuberculosis was evaluated. The results indicate that the compounds containing aromatic esters are more potent than alkyl ones. The most potent aromatic compound (R = 3-phenylpropyl) exhibits comparable anti-tubercular activity (MIC = 1 μmol/ml) with reference compound isoniazide (INH) (MIC = 1 μmol/ml). Conformational analysis, SAR studies of these compounds showed that increasing in lipophilicity and rotable bonds of these compounds resulted in increasing anti-tubercular activity.
- Khoshneviszadeh, Mehdi,Edraki, Najmeh,Javidnia, Katayoun,Alborzi, Abdolvahab,Pourabbas, Bahman,Mardaneh, Jalal,Miri, Ramin
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experimental part
p. 1579 - 1586
(2009/07/11)
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- Synthesis of ethyl 5-cyano-6-hydroxy-2-methyl-4-(1-naphthyl)-nicotinate
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A novel ethyl 5-cyano-6-hydroxy-2-methyl-4-(1-naphthyl)-nicotinate is successfully synthesized and the structure is determined by XRD, GC-MS analysis, element analysis and NMR spectroscopic in detail. A reaction mechanism for the reaction is proposed.
- Zhou, Yongchang,Kijima, Tatsuro,Kuwahara, Shunsuke,Watanabe, Masataka,Izumi, Taeko
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p. 3757 - 3761
(2008/09/21)
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- Iridium-catalyzed hydrogenation of β-dehydroamino acid derivatives using monodentate phosphoramidites
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The iridium-catalyzed asymmetric hydrogenation of 13 different β-dehydroamino acid derivatives to give optically active β-amino acid esters has been examined. Readily accessible monodentate octahydrobinaphthol- based phosphoramidites were used as chiral ligands. Good to excellent enantioselectivities and yields were obtained for the E isomers, whereas poorer catalyst performance was found for the Z isomers. Importantly, to obtain high enantioselectivity, substitution at the 3,3′-positions of the ligands was necessary. Enantioselectivities of up to 94% ee were achieved under optimized conditions. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Enthaler, Stephan,Erre, Giulia,Junge, Kathrin,Schroeder, Kristin,Addis, Daniele,Michalik, Dirk,Hapke, Marko,Redkin, Dmitry,Beller, Matthias
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experimental part
p. 3352 - 3362
(2009/04/07)
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- Development of practical rhodium phosphine catalysts for the hydrogenation of β-dehydroamino acid derivatives
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The rhodium-catalyzed asymmetric hydrogenation of various β-dehydroamino acid derivatives to give optically active β-amino acids has been examined. Chiral monodentate 4,5-dihydro-3H-dinaphthophosphepines, which are easily tuned and accessible in a multi-10-g scale, have been used as ligands. The enantioselectivity is largely dependent on the nature of the substituent at the phosphorous atom and on the structure of the substrate. Applying optimized conditions up to 94% ee was achieved.
- Enthaler, Stephan,Erre, Giulia,Junge, Kathrin,Holz, Jens,Boerner, Armin,Alberico, Elisabetta,Nieddu, Ilenia,Gladiali, Serafino,Beller, Matthias
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p. 568 - 577
(2012/12/31)
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- An efficient synthesis of 3-substituted 3H-pyrimidin-4-ones
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(Equation presented) A novel and practical synthesis of 3-substituted 3H-pyrimidin-4-ones is described. The key step involves the cyclization of enamide esters, derived from readily available β-keto esters, with trimethylaluminum and various primary amines.
- Jeong, Jae Uk,Chen, Xiaohong,Rahman, Attiq,Yamashita, Dennis S.,Luengo, Juan I.
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p. 1013 - 1016
(2007/10/03)
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- Solid-phase synthesis of pyrrolo[3,4-b]pyridines and related pyridine- fused heterocycles
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Sequential Hantzsch condensation and cyclative cleavage reactions have been used to define a novel solid-phase route to pyrrolo[3,4-b]pyridines and related pyridine-fused heterocycles. A combinatorial library of ~5000 compounds prepared via this chemistry is described.
- Bhandari, Ashok,Li, Bei,Gallop, Mark A.
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p. 1951 - 1960
(2007/10/03)
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- Synthesis and biological activity of some new 4-phenyl>-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid diesters
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The syntheses and pharmacological evaluation of a series of 4-phenyl>-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid diesters (4/7) are described.These compounds have been found to possess positive inotropic activity.
- Khadilkar, B. M.,Mestha, V. R.,Bhayade, S. R.
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p. 451 - 454
(2007/10/02)
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- Synthesis and comparative pharmacological studies of 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylates with non-identical ester functions
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Michael-addition of 3-aminocrotonic acid ester 7 to aralkylidene acetoacetic acid esters 6 is followed by ring closure to give novel 4-aryl-1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylates 8 with non-identical ester functions. In the series of 3-nitrophenyl derivatives (8, Ar=3-nitrophenyl) the pharmacological activities (coronary vasodilation, anti-hypertensive activity) of the asymmetrically substituted derivatives are shown to be superior to those of the corresponding symmetrically substituted derivatives in many cases. One representative of this class 3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedica rboxylate (nitrendipine, Bay e 5009, No. 3) was selected for further development as an antihypertensive drug.
- Meyer,Bossert,Wehinger,Stoepel,Vater
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p. 407 - 409
(2007/10/02)
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