- Design, synthesis and biological evaluation of chalcones as reversers of P-glycoprotein-mediated multidrug resistance
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Overexpression of P-glycoprotein (P-gp) is one of the major causes for multidrug resistance (MDR), which has become a major obstacle in cancer therapy. One hopeful approach to reverse the MDR is to develop inhibitors of P-gp in expression and/or function. Here, we designed and synthesized a series of chalcone derivatives as P-gp inhibitors and evaluated their potential reversal activities against MDR. Among them, the most active compound MY3 had little intrinsic cytotoxicity and showed the highest activity (RF = 50.19) in reversing DOX resistance in MCF-7/DOX cells. Further studies demonstrated that MY3 could increase intracellular accumulation of DOX and inhibit expression of P-gp at mRNA and protein levels. More importantly, MY3 significantly enhanced the efficacy of DOX against the tumor xenografts bearing MCF-7/DOX cells with the precondition of unchanged body weight. Therefore, MY3 might represent a promising lead to develop MDR reversal agents for cancer chemotherapy.
- Yin, Huanhuan,Dong, Jingjing,Cai, Yingchun,Shi, Ximeng,Wang, Hao,Liu, Guixia,Tang, Yun,Liu, Jianwen,Ma, Lei
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p. 350 - 366
(2019/07/19)
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- Nickel-Catalyzed Decarboxylation of Aryl Carbamates for Converting Phenols into Aromatic Amines
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Herein, we describe a new catalytic approach to accessing aromatic amines from an abundant feedstock, namely phenols. The most reliable catalytic method for converting phenols to aromatic amines uses an activating group, such as a trifluoromethane sulfonyl group. However, this activating group is eliminated as a leaving group during the amination process, resulting in significant waste. Our nickel-catalyzed decarboxylation reaction of aryl carbamates forms aromatic amines with carbon dioxide as the only byproduct. As this amination proceeds in the absence of free amines, a range of functionalities, including a formyl group, are compatible. A bisphosphine ligand immobilized on a polystyrene support (PS-DPPBz) is key to the success of this reaction, generating a catalytic species that is significantly more active than simple nonsupported variants.
- Nishizawa, Akihiro,Takahira, Tsuyoshi,Yasui, Kosuke,Fujimoto, Hayato,Iwai, Tomohiro,Sawamura, Masaya,Chatani, Naoto,Tobisu, Mamoru
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supporting information
p. 7261 - 7265
(2019/05/16)
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- Development and in Vitro Evaluation of a Microbicide Gel Formulation for a Novel Non-Nucleoside Reverse Transcriptase Inhibitor Belonging to the N-Dihydroalkyloxybenzyloxopyrimidines (N-DABOs) Family
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Preventing HIV transmission by the use of a vaginal microbicide is a topic of considerable interest in the fight against AIDS. Both a potent anti-HIV agent and an efficient formulation are required to develop a successful microbicide. In this regard, molecules able to inhibit the HIV replication before the integration of the viral DNA into the genetic material of the host cells, such as entry inhibitors or reverse transcriptase inhibitors (RTIs), are ideal candidates for prevention purpose. Among RTIs, S- and N-dihydroalkyloxybenzyloxopyrimidines (S-DABOs and N-DABOs) are interesting compounds active at nanomolar concentration against wild type of RT and with a very interesting activity against RT mutations. Herein, novel N-DABOs were synthesized and tested as anti-HIV agents. Furthermore, their mode of binding was studied by molecular modeling. At the same time, a vaginal microbicide gel formulation was developed and tested for one of the most promising candidates.
- Tintori, Cristina,Brai, Annalaura,Dasso Lang, Maria Chiara,Deodato, Davide,Greco, Antonia Michela,Bizzarri, Bruno Mattia,Cascone, Lorena,Casian, Alexandru,Zamperini, Claudio,Dreassi, Elena,Crespan, Emmanuele,Maga, Giovanni,Vanham, Guido,Ceresola, Elisa,Canducci, Filippo,Ari?n, Kevin K.,Botta, Maurizio
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p. 2747 - 2759
(2016/04/10)
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- INDUCTION OF GATA2 BY HDAC1 AND HDAC2 INHIBITORS
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Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with Gata2 deficiency, particularly diseases or disorders that involve any type of HDAC1 and/or HDAC2 expression. Such diseases include acute myeloid leukemia (AML); familial myelodysplastic syndrome (MDS); leukemia; sickle-cell anemia; beta-thalassemia; monocytopenia and mycobacterial infections; dendritic cell, nonocyte, B, and natural killer lymphoid deficiency; Emberger syndrome; asymptomatic neurocognitive impairment; mild neurocognitive disorder; and HIV- associated dementia.
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Page/Page column 68
(2016/05/02)
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- A TP-FRET-based two-photon fluorescent probe for ratiometric visualization of endogenous sulfur dioxide derivatives in mitochondria of living cells and tissues
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A ratiometric two-photon fluorescent probe for SO2 derivatives was first proposed based on acedan-merocyanine dyads via a TP-FRET strategy. It was successfully applied to visualization of the fluctuations of enzymatically generated SO2 derivatives in the mitochondria of HepG2 cells and rat liver tissues using two-photon fluorescence microscopy imaging.
- Yang, Xiaoguang,Zhou, Yibo,Zhang, Xiufang,Yang, Sheng,Chen, Yun,Guo, Jingru,Li, Xiaoxuan,Qing, Zhihe,Yang, Ronghua
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supporting information
p. 10289 - 10292
(2016/08/23)
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- Novel fluorinated amino-stilbenes and their solid-state photodimerization
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We synthesized a series of polyfluoro-amino-stilbenes in satisfactory yields by Wittig reaction of 4-piperazinyl-benzalhehydes with pentafluoro-benzylidene-triphenyl-phosphorane and we analyzed the photochemical behavior of these stilbenes in the solid st
- Papagni, Antonio,Buttero, Paola Del,Bertarelli, Chiara,Miozzo, Luciano,Moret, Massimo,Pryce, Mary T.,Rizzato, Silvia
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scheme or table
p. 2612 - 2621
(2011/01/12)
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- ANTIBACTERIAL AGENTS
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Antibacterial compounds of formula (I) are provided, as well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of such compounds.
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Page/Page column 155-156
(2009/01/24)
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- HYDRAZONE DERIVATIVE
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A compound represented by the following formula (I): wherein R1 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R2 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R3 represents hydrogen, etc.; Ar represents a divalent group derived from aromatic hydrocarbon, etc.; X represents a single bond, linear or branched alkylene having from 1 to 3 carbon atoms which may have a substituent, etc.; and G represents halogen, a saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc., a salt thereof or a solvate thereof; and an agent for inhibiting aggregation and/or deposition of an amyloid protein or an amyloid-like protein, which comprises the compound, a salt thereof or a solvate thereof
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Page/Page column 46
(2010/11/08)
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- Pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidine adenosine A2a receptor antagonists
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Compounds having the structural formula I or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, furanyl, thienyl, pyridyl, pyridyl N-oxide, oxazolyl or pyrrolyl, or cycloalkenyl R1, R2, R3, R4 and R5 are H, alkyl or alkoxyalkyl; and Z is optionally substituted aryl or heteroaryl are disclosed. Also disclosed is the use of compounds of formula I in the treatment of central nervous system diseases, in particular Parkinson's disease, alone or in combination with other agents for treating Parkinson's disease, and pharmaceutical compositions comprising them.
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Page/Page column 13
(2008/06/13)
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- 4,5-DIHYDRO-IMIDAZO[4,5,1-II]QUINOLIN-6-ONES AS PARP INHIBITORS
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Compounds of the formula 1, in which R1 and R2 have the meanings indicated in the description, are novel active PARP inhibitors.
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- PHENYLPYRIDINE CARBONYL PIPERAZINE DERIVATIVE
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The present invention relates to a compound which is represented by the following general formula and has type 4 phosphodiesterase inhibitory action, and uses and an intermediate compound thereof. (whereinR1, R2: hydrogen, a halogen, a lower alkyl, a lower alkoxy, or the like,R3, R4: hydrogen, a (substituted) lower alkyl, a halogen, or the like,R5: hydrogen, a lower alkyl, a lower alkoxycarbonyl, or the like, andn: 0 or 1).
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- Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
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Substituted quinolone derivatives in which an oxazolidinone, isoxazolinone, or isoxazoline is covalently bonded to a quinolone, methods of using the quinolone derivatives, and pharmaceutical compositions containing the quinolone derivatives are disclosed. Methods of synthesizing these substituted quinolone derivatives are also disclosed, and in particular a method of manufacturing a 7-(2-oxo-1,3-oxazolidin-3-yl)aryl-3-quinolinecarboxylic acid by condensing a 4-(2-oxo-1,3-oxazolidin-5-yl)aryl boronic acid with a 7-halo-quinolone derivative. The quinolone derivatives possess antibacterial activity, and are effective against a number of human and veterinary pathogens in the treatment of bacterial diseases.
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- Synthesis of novel succinamide derivatives having a 5,11-dihydro-6h- pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton as potent and selective M2 muscarinic receptor antagonists. II
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A series of succinamide derivatives containing the 5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton (6a-z) was prepared and evaluated for binding affinity to muscarinic receptors in vitro and for antagonism of bradycardia and salivation in vivo in comparison with AF-DX 116 (1a). Structure-activity relationships (SAR) studies in vitro indicated that the 4-(4-alkyl-1-piperazinyl)benzylamino moiety plays a crucial role in enhancing the infinity for M2 muscarinic receptors. Compound 6y, containing a 4-(4-isopropyl-1-piperazinyl)benzylmethylamino moiety, exhibited the highest affinity for M2 muscarinic receptors (pK(i) = 9.2), being 200 times as potent as 1a, and compound 6u, containing a 4-(4-ethyl-1- piperazinyl)benzylethylamino moiety, showed the highest selectivity for M2 over M3 muscarinic receptors (M3/M2 ratio=320). Both 6y and 6u antagonized the oxotremorine-induced bradycardia in rats after intravenous or oral administration. Oral evaluation in conscious dogs showed that the efficacy for increasing the heart rate was at least 3-fold greater than that of 1a.
- Watanabe, Toshihiro,Kakefuda, Akio,Kinoyama, Isao,Takizawa, Kenji,Hirano, Seiko,Shibata, Hiroshi,Yanagisawa, Isao
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p. 1458 - 1469
(2007/10/03)
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