- Design and synthesis of tetrahydropyridopyrimidine derivatives as dual GPR119 and DPP-4 modulators
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Based on the approach of merged pharmacophores of GPR119 agonists and DPP-4 inhibitors, a series of tetrahydropyridopyrimidine compounds were designed as dual GPR119 and DPP-4 modulators with hypoglycemic activity. Seven fragments extracted from DPP-4 inhibitors were hybridized with the scaffold of tetrahydropyridopyrimidine. Among them, compound 51 displayed most potent GPR119 agonistic activity (EC50 = 8.7 nM) and good inhibition rate of 74.5% against DPP-4 at 10 μM. Furthermore, the blood glucose AUC0-2h of 51 was reduced to 19.5% in the oral glucose tolerance test (oGTT) at the dose of 30 mg/kg in C57BL/6N mice, which was more potent than that of vildagliptin (16.4%) at the same dose. The docking study of compound 51 with DPP-4 indicated GPR119 agonists could inhibit DPP-4 to serve as dual GPR119 and DPP-4 modulators.
- Fang, Yuanying,Zhang, Shaokun,Wu, Wenting,Liu, Yanhua,Yang, Juan,Li, Yuyuan,Li, Min,Dong, Huanhuan,Jin, Yi,Liu, Ronghua,Yang, Zunhua
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- Synthesis and evaluation of novel fused pyrimidine derivatives as GPR119 agonists
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A novel series of fused pyrimidine derivatives were designed, synthesized and evaluated as GPR119 agonists. Among them, cyclohexene fused compounds (tetrahydroquinazolines) showed greater GPR119 agonistic activities than did dihydrocyclopentapyrimidine and tetrahydropyridopyrimidine scaffolds. Analogues (16, 19, 26, 28, 42) bearing endo-N-Boc-nortropane amine and fluoro-substituted aniline exhibited better EC50 values (0.27–1.2 μM) though they appeared to be partial agonists.
- Fang, Yuanying,Xiong, Lijuan,Hu, Jianguo,Zhang, Shaokun,Xie, Saisai,Tu, Liangxing,Wan, Yang,Jin, Yi,Li, Xiang,Hu, Shaojie,Yang, Zunhua
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p. 103 - 111
(2019/01/28)
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- Cultivation of a Cu/HMPC catalyst from a hyperaccumulating mustard plant for highly efficient and selective coupling reactions under mild conditions
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Cu-containing activated carbon (eco-catalyst, Cu/HMPC, where 'C' defines 'carbon') was derived from a metal-hyperaccumulating mustard plant (HMP) by a simple chemical activation method. Transmission electron microscopy/selected area diffraction (HRTEM/SAED) results revealed that the Cu/HMPC has mainly three types of morphology [sheet-like morphology (2D), hollow-spheres (3D) and needle-like structures (1D)] which are interconnected. HRTEM-SAED, Raman and X-ray photoelectron spectroscopy (XPS) results confirmed the existence of Cu oxide species in Cu/HMPC. Content of Cu in Cu/HMPC was determined to be 1.03 wt%. The quality of graphitization in Cu/HMPC was discussed by using Raman and XRD results. The BET surface area of Cu/HMPC was determined to be 620.8 m2 g-1. The Cu/HMPC actively transformed a wide range of amines to imines under very mild reaction conditions. The catalyst Cu/HMPC gave products in excellent yields (98-61%) with very high TON/TOF values (1512/339-833/35 h-1). To the best of our knowledge, this is the most efficient Cu-based heterogeneous eco-catalyst for the synthesis of imines among those reported to date. The Cu can be recovered from used Cu/HMPC by a simple HCl treatment. Versatility, heterogeneity and reusability of Cu/HMPC were tested. A possible mechanism has been proposed.
- Gopiraman, Mayakrishnan,Wei, Kai,Zhang, Ke-Qin,Chung, Ill-Min,Kim, Ick Soo
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p. 4531 - 4547
(2018/02/09)
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- Ferrocene-containing Impiridone (ONC201) Hybrids: Synthesis, DFT modelling, in vitro evaluation, and structure–activity relationships
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Inspired by the well-established clinical evidence about the interplay between apoptotic TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) mechanism and reactive oxygen species (ROS)-mediated oxidative stress, a set of novel ONC201 hybrids containing the impiridone core and one or two differently positioned ferrocenylalkyl groups were synthesised in our present work. These two types of residues have been implicated in the aforementioned mechanisms associated with cytotoxic activity. A straightforward, primary amine-based synthetic approach was used allowing the introduction of a variety of N-substituents into the two opposite regions of the heterocyclic skeleton. Reference model compounds with benzyl and halogenated benzyl groups were also synthesised and tested. The in vitro assays of the novel impiridones on five malignant cell lines disclosed characteristic structure-activity relationship (SAR) featuring significant substituent-dependent activity and cell-selectivity. A possible contribution of ROS-mechanism to the cytotoxicity of the novel metallocenes was suggested by density functional theory (DFT)studies on simplified models. Accordingly, unlike the mono-ferrocenylalkyl-substituted products, the compounds containing two ferrocenylalkyl substituents in the opposite regions of the impiridone core display a much more pronounced long-term cytotoxic effect against A-2058 cell line than do the organic impiridones including ONC201 and ONC212. Furthermore, the prepared bis-metallocene derivatives also present substantial activity against COLO-205- and EBC-1 cell lines.
- Bárány, Péter,Oláh, Rita Szabó,Kovács, Imre,Czuczi, Tamás,Szabó, Csenge Lilla,Takács, Angéla,Lajkó, Eszter,Láng, Orsolya,Ohidai, László K.,Schlosser, Gitta,Osze, Szilvia B.,Mez o, Gábor,Hudecz, Ferenc,Csámpai, Antal
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- SUBSTITUTED PHENYLOXAZOLIDINONES FOR ANTIMICROBIAL THERAPY
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The present invention relates to novel oxazolidinones (Formula I): or a pharmaceutically acceptable salt having ring A characterized by N-containing monocyclic, bicyclic or spirocyclic substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.
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Page/Page column 30
(2017/02/09)
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- New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility
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Curcumin, the main curcuminoid of the popular Indian spice turmeric, is a potent chemopreventive agent and useful in many different diseases. A major limitation of applicability of curcumin as a health promoting and medicinal agent is its extremely low bioavailability due to efficient first pass metabolism, poor gastrointestinal absorption, rapid elimination, and poor aqueous solubility. In the present study, nanotechnology was selected as a choice approach to enhance the bioavailability of the curcuminis. A new polyamidoamine dendrimer (G0.5) was synthesized, characterized, and tested for cytotoxicity in human breast cancer cells (MCF-7). No cytotoxicity of G0.5 was found in the range between 10?3 and 3 × 10?8 M. Consequently, G0.5 was used to prepare spherical nanoparticles of ca. 150 nm, which were loaded with curcumin [molar ratio G0.5/curcumin 1 : 1 (formulation 1) and 1 : 0.5 (formulation 2)]. Remarkably, the occurrence of a single population of nanoparticles having an excellent polydispersity index ( 0.20) was found in both formulations. Formulation 1 was selected to test in vitro drug release because it was superior in terms of encapsulation efficiency (62 %) and loading capacity (32 %). The solubility of curcumin was increased ca. 415 and 150 times with respect to the unformulated drug, respectively, for formulation 1 and formulation 2. The release of curcumin from the nanoparticles showed an interesting prolonged and sustained release profile.
- Falconieri, Maria Cristina,Adamo, Mauro,Monasterolo, Claudio,Bergonzi, Maria Camilla,Coronnello, Marcella,Bilia, Anna Rita
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p. 420 - 425
(2017/03/21)
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- RECYCLABLE CATALYSTS FOR CHLORINATION OF ORGANIC ACIDS AND ALCOHOLS
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The present invention discloses recyclable polymeric catalyst of Formula I, for chlorination of organic acids and alcohols using chlorinating agents such as carbonyl chloride, oxalyl chloride or thionyl chloride, wherein, ‘m’ on the pendent groups on polystyrene backbone can have values from 1 to 5 and R is the alkyl group ranging from C1 to C5.
- -
-
Paragraph 0077-0079
(2017/10/10)
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- Penfluridol preparation method
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The invention discloses a penfluridol preparation method. The penfluridol preparation method includes the following steps of 1), subjecting succinic anhydride and fluorobenzene to Friedel-Crafts reaction prior to acid decomposition, and collecting a compound from the formula 2) as is shown in the description; 2), putting the compound in a solvent to collect a compound in formula 3) as is shown in the description in a solvent reduced through a reducing agent; 3), putting the compound into the fluorobenzene to perform the Friedel-Crafts reaction to collect a compound in the formula 4) as is shown in the description; subjecting the compound and ethyl chloroformate to action to generate a compound in formula 5) as is shown in the description; 5), subjecting the compound and a compound shown in formula (XVII) to reaction prior to hydrolyzation to collect a compound in formula 6) as is shown in the description; 6), performing reduction with the reducing agent prior to hydrolyzing a reduction product and then collecting penfluridol (I). The penfluridol preparation method is high in yield, low in cost, moderate in reaction condition, short in circuit, proper for industrial production, low in three wastes, easy to treat and suitable for industrial production.
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- Thermodynamically controlled chemoselectivity in lipase-catalyzed aza-Michael additions
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Chemoselective synthesis of N-protected β-amino esters involving lipase-catalyzed aza-Michael additions and α,β-unsaturated precursors is mainly hampered by the two electrophilic sites present on these compounds. In order to control the chemoselectivity a solvent engineering strategy based on the thermodynamic behaviour of products in media of different polarity was designed. This strategy allowed to obtain aza-Michael adducts from benzylamine and different acrylates with high selectivity. In almost all reactions carried out in n-hexane, a non-polar solvent, aminolysis was avoided while the corresponding Michael adducts were exclusively synthesized in 53-78% yields. On the contrary, in reactions carried out in a polar solvent such as 2-methyl-2-butanol the aminolysis products were favoured. Thermodynamic analyses of these processes using the COSMO-RS method helped to understand some of the key factors affecting chemoselectivity and confirmed that a reliable estimation of the thermodynamic interactions of solutes and solvents allows an adequate selection of a reaction media that may lead to chemoselectivity.
- Rivera-Ramírez, José Domingo,Escalante, Jaime,López-Munguía, Agustín,Marty, Alain,Castillo, Edmundo
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supporting information
p. 76 - 82
(2015/01/30)
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- Selective N-alkylation of primary amines with R-NH2·HBr and alkyl bromides using a competitive deprotonation/protonation strategy
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Monoalkylation of primary amines using amine hydrobromides and alkyl bromides has been carried out. Under controlled reaction conditions the reactant primary amine was selectively deprotonated and made available for reaction, while the newly generated secondary amine remained protonated, and did not participate in alkylation further. Reaction was carried out under mild reaction conditions and was applicable to a wide range of primary amines and alkyl bromides.
- Bhattacharyya, Shubhankar,Pathak, Uma,Mathur, Sweta,Vishnoi, Subodh,Jain, Rajeev
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p. 18229 - 18233
(2014/05/20)
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- Carbon dioxide as a reversible amine-protecting agent in selective Michael additions and acylations
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Carbon dioxide can be used as a temporary protecting group for amines. A carbamic acid is formed reversibly when CO2 is bubbled through a solution of a sufficiently basic primary amine at room temperature and atmospheric pressure. This reaction is employed for the protection of the amine functionality in several reactions at room temperature where inter- or intramolecular selectivity is desired. The concept is demonstrated for the selective Michael additions to methyl acrylate of a normally less reactive sulfonamide in the presence of a strong amine nucleophile, or of a cyclic secondary amine in the presence of an aliphatic primary amine, or of a β-ketoester in the presence of amines. The selective acylation of an alcohol in the presence of an amine can be achieved under a CO2 atmosphere as well.
- Peeters, Annelies,Ameloot, Rob,De Vos, Dirk E.
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p. 1550 - 1557
(2013/09/24)
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- Synthesis of a series of carbon-14 labeled tetrahydropyrido[4,3-d] pyrimidin-4(3H)-ones
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A series of tetrahydropyrido[4,3-d]pyrimidin-4(3H)-ones labeled with carbon-14 in the 2-position of pyrimidinone moiety were prepared as part of a 3-step sequence from benz[amidino-14C]amidine hydrochloride as a key synthetic intermediate. Copyright
- Arjomandi, Omid Khalili,Saemian, Nader,McGeary, Ross P.,Shirvani, Gholamhossein
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p. 722 - 725
(2014/01/06)
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- 1-[(4-HYDROXYPRIDIN-4-YL) METHYL]PYRIDINE-2(1H)-ONE DERIVATIVES, PREPARATION METHODS AND USES THEREOF
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Provided are N-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives represented by formula I, stereoisomers, pharmaceutically acceptable salts or solvates thereof
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Paragraph 0062
(2013/03/28)
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- 1-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives, preparation methods and uses thereof
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Provided are N-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives represented by formula I, stereoisomers, pharmaceutically acceptable salts or solvates thereof. The above compounds have the dual activities of 5-hydroxytryptamine 1A receptor ligand and selective serotonin reuptake inhibitor. The preparation methods of the above compounds, the uses of these compounds for the prevention or treatment of nervous system diseases related to 5-hydroxytryptamine system dysfunction and the pharmaceutical compositions containing these compounds are also provided.
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Paragraph 0100
(2013/09/12)
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- Novel symmetrical trans-bis-Schiff bases of N-substituted-4- piperidones: Synthesis, characterization, and preliminary antileukemia activity mensurations
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A series of novel symmetrical trans-bis-Schiff bases (11a, 11b, 11c, 11d, 11e, 11f, 11g, 11h, 11i, 11j, 11k, 11l, 11m) were designed and prepared as novel anticancer analogues, with the trans-configuration confirmed by X-ray diffraction. Preliminary inhibitory effects of these compounds on CML K562 cell growth were investigated, and the potential analogue 11e showed an excellent anti-leukemia activity (IC50=6.35 μg/mL), which is higher than that of the clinical drug 5-fluorouracil (IC50=8.48 μg/mL). Complete assignments had been achieved for the title compounds by spectroscopic techniques, and their structure-activity relationships have been studied.
- Sun, Chuan-Wen,Wang, Hai-Feng,Zhu, Jun,Yang, Ding-Rong,Xing, Jiahua,Jin, Jia
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p. 1374 - 1380
(2014/01/06)
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- Aza-Michael addition of aliphatic or aromatic amines to α,β-unsaturated compounds catalyzed by a DBU-derived ionic liquid under solvent-free conditions
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A task-specific ionic liquid, 1,8-diazabicyclo[5.4.0]-undec-7-en-8-ium acetate has been successfully used as a catalyst for aza-conjugate addition of aliphatic or aromatic amines to various electron deficient alkenes under solvent-free conditions and at room temperature. The catalyst can be reused for six times without noticeable loss of activity.
- Ying, An-Guo,Liu, Luo,Wu, Guo-Feng,Chen, Gang,Chen, Xin-Zhi,Ye, Wei-Dong
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experimental part
p. 1653 - 1657
(2009/06/28)
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- Michael additions of amines to methyl acrylates promoted by microwave irradiation
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A simple and efficient protocol has been developed for the Michael addition of amines to α,β-unsaturated esters under microwave irradiation. Under these conditions there was a significant decrease in the reaction time, increases in the yields and increased purity of the products.
- Escalante, Jaime,Carrillo-Morales, Manuel,Linzaga, Irma
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p. 340 - 347
(2008/09/17)
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- Understanding the structural requirements of 4-anilidopiperidine analogues for biological activities at μ and δ opioid receptors
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New 4-anilidopiperidine analogues in which the phenethyl group of fentanyl was replaced by several aromatic ring-contained amino acids (or acids) were synthesized to study the biological effect of the substituents on μ and δ opioid receptor interactions. These analogues showed broad (47 nM-76 μM) but selective (up to 17-fold) binding affinities at the μ opioid receptor over the δ opioid receptor, as predicted from the message-address concept.
- Lee, Yeon Sun,Nyberg, Joel,Moye, Sharif,Agnes, Richard S.,Davis, Peg,Ma, Shou-wu,Lai, Josephine,Porreca, Frank,Vardanyan, Ruben,Hruby, Victor J.
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p. 2161 - 2165
(2008/02/01)
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- Convenient formal synthesis of (±)-paroxetine
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A formal total synthesis of antidepressant (±)-paroxetine employing a solvent-free Heck reaction is disclosed. Copyright Taylor & Francis Group, LLC.
- Chavan, Subhash P.,Khobragade, Dushant A.,Pathak, Ashok B.,Kalkote, Uttam R.
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p. 3143 - 3149
(2008/02/13)
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- Cellulose-supported copper(0) catalyst for aza-Michael addition
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Cellulose-supported copper(0) efficiently catalyzes the aza-Michael reaction of N-nucleophiles, such as amines and imidazoles with α,β-unsaturated compounds to produce the corresponding β-amino compounds and N-substituted imidazoles in excellent yields. The reactions are facile and the recovered catalyst is used for several cycles with consistent activity. Georg Thieme Verlag Stuttgart.
- Reddy, K. Rajender,Kumar, Nadakudity S.
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p. 2246 - 2250
(2007/10/03)
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- Ceric ammonium nitrate catalyzed aza-Michael addition of aliphatic amines to α,β-unsaturated carbonyl compounds and nitriles in water
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Ceric ammonium nitrate (3 mol%) efficiently catalyzes the aza-Michael reaction of amines with α,β-unsaturated carbonyl compounds in water to produce the corresponding β-amino carbonyl compounds in good to excellent yields (55-99%) for most of the compounds under mild conditions. The reaction is procedurally simple and displays limited chemoselectivity, as aromatic amines were found to be unreactive. Georg Thieme Verlag Stuttgart.
- Varala, Ravi,Sreelatha, Nuvula,Adapa, Srinivas R.
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p. 1549 - 1553
(2007/10/03)
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- Zirconium(IV) chloride-mediated chemoselective conjugate addition of aliphatic amines to α,β-ethylenic compounds
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Zirconium chloride efficiently catalyzes the conjugate addition of a variety of aliphatic amines to α,β-unsaturated ester, nitriles, and ketones to give the corresponding β-amino derivatives in excellent yields under mild reaction conditions. Aromatic amines do not participate in this transformation. Copyright Taylor & Francis Group, LLC.
- Meshram,Lakshindra,Reddy,Sadashiv,Yadav
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p. 795 - 801
(2007/10/03)
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- Cu(acac)2 immobilized in ionic liquids: A recoverable and reusable catalytic system for aza-Michael reactions
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Copper(II) acetylacetonate immobilized in ionic liquids efficiently catalyzes the aza-Michael reaction of amines with α,β-unsaturated carbonyl compounds to produce the corresponding β-amino carbonyl compounds with great alacrity in excellent yields. The reactions are far more facile than those reported earlier. The recovered ionic liquid phase containing the copper catalyst can be reused for several cycles with consistent activity.
- Kantam, M. Lakshmi,Neeraja,Kavita,Neelima,Chaudhuri, Mihir K.,Hussain, Sahid
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p. 763 - 766
(2007/10/03)
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- MULTIPURPOSE LINKER COMPOUNDS AND LIGANDS AND PROCESS FOR PRODUCING THE SAME
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A versatile linker compound has a structure represented by following general formula (1), wherein Y has a structure represented by O or NH, and X has a structure serving as a multi-branched moiety including four hydrocarbon derivative chains each of which has an aromatic amino group at an end thereof, and may or may not have a carbon-nitrogen bond in a backbone thereof. With the versatile linker compound, sugar molecules can be two-dimensionally arranged on a surface of a protein-analyzing supporter with high reproducibility. Also, a ligand includes the versatile linker compound and a sugar molecule introduced thereinto.
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Page/Page column 15
(2010/02/12)
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- A green, ionic liquid and quaternary ammonium salt-catalyzed aza-Michael reaction of α,β-ethylenic compounds with amines in water
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The first environmentally benign, highly efficient conjugate addition of aliphatic amines to α,β-unsaturated compounds catalysed by simple quaternary ammonium salts and ionic liquids in the green solvent, water, is described.
- Xu, Li-Wen,Li, Jing-Wei,Zhou, Shao-Lin,Xia, Chun-Gu
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p. 183 - 184
(2007/10/03)
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- Aza-Michael Reactions in Ionic Liquids. A Facile Synthesis of β-Amino Compounds
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Electron-deficient olefins undergo smoothly aza-Michael reactions with a wide range of amines in ionic liquids in the absence of any acid catalyst to produce the corresponding β-amino compounds in excellent yields with high 1,4-selectivity. The recovered ionic liquids can be reused in subsequent reactions without loss of activity. Owing to the high polarity of ionic liquids, the enones show enhanced reactivity thereby reducing reaction times and improving the yields significantly.
- Yadav,Reddy,Basak,Narsaiah
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p. 988 - 989
(2007/10/03)
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- Synthesis and Stereochemistry of Some 3-Azabicyclo[3.3.1]nonane Derivatives
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Michael reactions of methyl (ethyl) 1-benzyl-4-oxopiperidine-3- carboxylates with a number of α,β-unsaturated carbonyl compounds result in formation of 6- and 6,8-substituted methyl (ethyl) 3-benzyl-9-oxo-3-azabicyclo[3.3.1]nonane-1-carboxylates. Stereochemical aspects of these reactions were studied, and some further transformations of the products were performed.
- Vafina,Yakhina,Khakimova,Spirikhin,Galin,Yunusov
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- Indium trichloride-catalyzed conjugate addition of amines to α,β-ethylenic compounds in water
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Catalytic amount of indium (III) trichloride efficiently catalyzed Michael reaction between amines and α,β-ethylenic compounds in water and under mild conditions. Indium trichloride can be recovered and reused without decrease in yield.
- Loh, Teck-Peng,Wei, Lin-Li
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p. 975 - 976
(2007/10/03)
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- N-SULFONYLINDOLINE DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS IN WHICH THEY ARE PRESENT
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The invention relates to N-sulfonyl derivatives of formulae (I) " and (I)' STR1 and to pharmaceutical compositions in which they are present. The compounds have an affinity for the vasopressin and ocytocin receptors. "
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