1486-54-0Relevant articles and documents
Synthesis and protein kinase C inhibitory activities of balanol analogues with modification of 4-hydroxybenzamido moiety
Hu, Hong,Mendoza, Jose S.,Lowden, Christopher T.,Ballas, Lawrence M.,Janzen, William P.
, p. 1873 - 1882 (1997)
A series of racemic balanol analogues with modification of the benzamido moiety of balanol have been synthesized and evaluated for their inhibitory activities against human protein kinase C isozymes (PKC-alpha, -beta I, -beta II, -gamma, -delta, -epsilon, and -eta). The structural modification includes replacement of the 4-hydroxyphenyl group with variously substituted phenyl rings, substitution of the amide linkage with a sulfonamide or an ester, and replacement of the 4-hydroxyphenyl substructure with a hydroxyl substituted indole or a hydroxybenzyl group. In general, these analogues were found to be less potent than balanol, but a number of analogues were identified with improved isozyme selectivity. The structure-activity relationship studies of these analogues also indicated that (1) the optimal general PKC inhibition requires a free 4-hydroxyl group in the benzamido portion of the molecule, (2) the amide linkage of the benzamido moiety is important for PKC inhibition, and (3) the conformation associated with the benzamido moiety seems to have a profound effect on PKC inhibition. The requirement of a free 4-hydroxyl group in conjunction with an appropriate conformation of the benzamido moiety for optimal PKC inhibition suggests that the 4-hydroxyphenyl group may be involved in a specific inhibitor-enzyme interaction important for PKC inhibition.
COMPOSITIONS AND METHODS FOR GLUCOSE TRANSPORT INHIBITION
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Page/Page column 27-28, (2011/10/13)
Glucose deprivation is an attractive strategy in cancer research and treatment. Cancer cells upregulate glucose uptake and metabolism for maintaining accelerated growth and proliferation rates. Specifically blocking these processes is likely to provide new insights to the role of glucose transport and metabolism in tumorigenesis, as well as in apoptosis. As solid tumors outgrow the surrounding vasculature, they encounter microenvironments with a limited supply of nutrients leading to a glucose deprived environment in some regions of the tumor. Cancer cells living in the glucose deprived environment undergo changes to prevent glucose deprivation-induced apoptosis. Knowing how cancer cells evade apoptosis induction is also likely to yield valuable information and knowledge of how to overcome the resistance to apoptosis induction in cancer cells. Disclosed herein are novel anticancer compounds that inhibit basal glucose transport, resulting in tumor suppression and new methods for the study of glucose deprivation in animal cancer research.
CEPHALOSPORIN HAVING CATECHOL GROUP
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Page/Page column 63-64, (2011/07/30)
The present invention provides Cephem compounds which have a wide antimicrobial spectrum and have potent antimicrobial activity against beta-lactamase producing Gram negative bacteria as follows: A compound of the formula: wherein, X is N, CH or C-Cl; T is S or the like; A and G are lower alkylene or the like; B is a single bond or the like; D is a single bond, -NR7-, -CO-, -CO-NR7-, -NR7-CO-, -NR7-CO-NR7-, or the like; E is optionally substituted lower alkylene; F is a single bond or optionally substituted phenylene; R3, R4, R5 and R6 each is independently hydrogen, halogene, nitrile, or the like; or an ester, a compound protected at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof.
Novel inhibitors of basal glucose transport as potential anticancer agents
Zhang, Weihe,Liu, Yi,Chen, Xiaozhuo,Bergmeier, Stephen C.
scheme or table, p. 2191 - 2194 (2010/06/15)
Cancer cells commonly show increased levels of glucose uptake and dependence. A potential strategy for the treatment of cancer may be the inhibition of basal glucose transport. We report here the synthesis of a small library of polyphenolic esters that inhibit basal glucose transport in H1299 lung and other cancer cells. These basal glucose transport inhibitors also inhibit cancer cell growth in H1299 cells, and these two activities appear to be correlated.
Synthesis and characterization of ruthenium(II)-pyridylamine complexes with catechol pendants as metal binding sites
Kojima, Takahiko,Hirasa, Norihisa,Noguchi, Daisuke,Ishizuka, Tomoya,Miyazaki, Soushi,Shiota, Yoshihito,Yoshizawa, Kazunari,Fukuzumi, Shunichi
experimental part, p. 3737 - 3745 (2010/06/18)
A novel tris(2-pyridylmethyl)amine (TPA) derivate having two catechol moieties linked by amide linkages at the 6-positions of two pyridyl groups was synthesized. The ligand, N,N-bis[6-{3,4-(dihydroxy)benzamide}-2-pyridyl-methyl]- N-(2-pyridylmethyl)amine (Cat2-TPA; L2), and its precursor, N,N-bis[6-{3,4-bis(benzyloxy)-benzamide}-2-pyridyl-methyl]-N-(2-pyridylmethyl) -amine ((Bn2Cat)2-TPA; L1), formed stable ruthenium(II) complexes, [RuCl(L2)]PF6 (2) and [RuCl(L1)]PF6 (1), respectively. The crystal structure of [RuCl(L2)]Cl (2′) was determined by X-ray crystallography to show two isomers in terms of the orientation of one catechol moiety. In complex 2, the ligand bearing catechols acts as a pentadentate ligand involving coordination of one of the amide oxygen atoms in addition to that of the tetradentate TPA moiety and two metal-free catechol moieties as metal-binding sites. The coordination of L2 results in the preorganization of the two catechols to converge them to undergo intramolecular π-π interactions. The 1H NMR spectrum of 2 in DMSO-d 6 revealed that only one isomer was present in the solution. This selective formation could be ascribed to the formation of an intramolecular hydrogen-bonding network among the hydroxyl groups of the catechol moieties, as suggested by X-ray analysis. This intramolecular hydrogen bonding could differentiate the pKa values of the hydroxy groups of the catechol moieties into three kinds, as indicated by spectroscopic titration with tetramethylammonium hydroxide (TMAOH) in DMF. The complexation of 2 with other metal ions was also examined. The reaction of 2 with [Cu(NO3) 2(TMEDA)] (TMEDA = N,N,N′,N′-tetramethylethylenediamine) in methanol allowed us to observe the selective formation of a binuclear complex, [RuCl(L22-){Cu(TMEDA)}]PF6 (3), which was characterized by ESI-MS, UV-vis, and ESR spectroscopies. Its ESR spectrum in methanol suggested that the coordination of the Cu(II)-TMEDA unit to the converged catechol moieties would be different from conventional κ2-O,O′:η2-coordination: it exhibits a novel bridging coordination mode, bis-κ1-O:η1- coordination, to form the binuclear Ru(II)-Cu(II) complex.
Synthesis and structure-function analysis of Fe(II)-form-selective antibacterial inhibitors of Escherichia coli methionine aminopeptidase
Wang, Wen-Long,Chai, Sergio C.,Ye, Qi-Zhuang
scheme or table, p. 1080 - 1083 (2009/08/07)
Methionine aminopeptidase (MetAP) is a promising target for the development of novel antibacterial, antifungal and anticancer therapy. Based on our previous results, catechol derivatives coupled with a thiazole or thiophene moiety showed high potency and selectivity toward the Fe(II)-form of Escherichia coli MetAP, and some of them clearly showed antibacterial activity, indicating that Fe(II) is likely the physiologically relevant metal for MetAP in E. coli and other bacterial cells. To further understand the structure-function relationship of these Fe(II)-form selective MetAP inhibitors, a series of catechol derivatives was designed and synthesized by replacement of the thiazole or thiophene moiety with different five-membered and six-membered heterocycles. Inhibitory activities of these newly synthesized MetAP inhibitors indicate that many five- and six-membered rings can be accommodated by MetAP and potency on the Fe(II)-form can be improved by introducing substitutions on the heterocyles to explore additional interactions with the enzyme. The furan-containing catechols 11-13 showed the highest potency at 1 μM on the Fe(II)-form MetAP, and they were also among the best inhibitors for growth inhibition against E. coli AS19 strain. These findings provide useful information for the design and discovery of more effective MetAP inhibitors for therapeutic applications.
Total Synthesis of Petrobactin and Its Homologues as Potential Growth Stimuli for Marinobacter hydrocarbonoclasticus, an Oil-Degrading Bacteria
Gardner, Richard Andrew,Kinkade, Rebecca,Wang, Chaojie,Phanstiel IV, Otto
, p. 3530 - 3537 (2007/10/03)
A modular synthesis was developed to access petrobactin, a catechol-containing siderophore isolated from Marinobacter hydrocarbonoclasticus. A range of petrobactin homologues with differing dihydroxybenzamide motifs and in one case an increased number of
Total synthesis and structure revision of petrobactin
Bergeron, Raymond J.,Huang, Guangfei,Smith, Richard E.,Bharti, Neelam,McManis, James S.,Butler, Alison
, p. 2007 - 2014 (2007/10/03)
The total synthesis and the revised structural assignment of petrobactin, a siderophore isolated from the marine bacterium Marinobacter hydrocarbonoclasticus, is reported. The key step in the synthesis involved condensation of N1-(2,3-dibenzoyl
COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES SUCH AS ALZHEIMER'S DISEASE, TYPE 2 DIABETES, AND PARKINSON'S DISEASE
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Page 40, (2008/06/13)
Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially A? amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinophathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.
An improved synthesis of the anti-picornavirus flavone 3-O-methylquercetin
Boers, Frank,Deng, Bo-Liang,Lemiere, Guy,Lepoivre, Jozef,De Groot, Alex,Dommisse, Roger,Vlietinck, Arnold J.
, p. 313 - 316 (2007/10/03)
Two optimised procedures to synthesise 3-O-methylquercetin (1), an important antivirally active flavone, are presented: one is based on an Allan-Robinson condensation, the other one on a modified phase transfer catalysed Baker-Venkataraman transformation.
