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1.
Xavier NM Goulart M Neves A Justino J Chambert S Rauter AP Queneau Y 《Bioorganic & medicinal chemistry》2011,19(2):926-938
The synthesis of a series of pyranoid derivatives comprising a conjugated carbonyl function and related triazole derivatives, structurally suitable for bioactivity evaluation, was achieved in few steps starting from readily available carboxymethyl glycoside lactones (CMGL). 3-Enopyranosid-2-uloses were generated by oxidation/elimination of tri-O-acylated 2-hydroxy pyranosides. Subsequent Wittig olefination provided stereoselectively 2-C-branched-chain conjugated dienepyranosides with (E)-configuration around the exocyclic double bond. A heterogeneous CuI/Amberlyst-catalyzed ‘click’ chemistry protocol was used to convert glycosides bearing a propargyl moiety into the corresponding 1,2,3-triazoles. These new molecules were screened for their in vitro antibacterial and antifungal activities and those containing conjugated carbonyl systems demonstrated the best efficacy. (N-Dodecylcarbamoyl)methyl enone glycerosides were the most active ones among the enones tested. The ??-anomer displayed very strong activities against Bacillus cereus and Bacillus subtilis and strong activity toward Enterococcus faecalis and the fungal pathogen Penicillium aurantiogriseum. The corresponding ??-anomer presented a very strong inhibitory effect against two fungal species (Aspergillus niger and P. aurantiogriseum). (N-Dodecyl-/N-propargyl/or N-benzylcarbamoyl)methyl dienepyranosides exhibited selectively a strong activity toward E. faecalis. Further acute toxicity evaluation indicated low toxic effect of the (N-dodecylcarbamoyl)methyl enone glyceroside ??-anomer and of the carbamoylmethyl dienepyranosides N-protected with propargyl or benzyl groups. 相似文献
2.
Pace-Asciak CR 《Molecular neurobiology》2005,32(1):19-26
This article reviews a lecture I was honored to present at the Leon Wolfe Symposium in Montreal on March 25, 2004. The lecture
described my research career, which started with my interaction with Wolfe at the Montreal Neurological Institute as a postdoctoral
fellow and research associate and was followed by additional research discoveries after I left Montreal for my first academic
position at the Research Institute, The Hospital for Sick Children and University of Toronto. The article consists of two
parts. The first part involves the discovery (in Wolfe’s laboratory) of a new pathway of arachidonic acid, in which a bicyclic
prostanoid structure (later called prostacyclin by John Vane and his group) was described, and its further development in
Toronto, which led to the discovery of the conversion of the bicyclic prostanoid into 6-keto prostaglandin F1α. The second part deals with the hepoxilin pathway, a pathway I discovered during a sabbatical leave in Japan with Professor
Shozo Yamamoto, which was followed by a stay of several months in the laboratory of Professor Bengt Samuelsson in Sweden.
I deal with the historical aspects of both pathways and end with interesting novel aspects of hepoxilin stable antagonist
analogs in the treatment of solid tumors in experimental animals. 相似文献
3.
《Bioorganic & medicinal chemistry letters》2014,24(11):2555-2559
The MAPK pathway is identified as one of the most important pathways involved in cell proliferation and differentiation. A key kinase in the pathway, the Mitogen-activated protein kinase kinase (MEK) is recognized as a promising target for antitumor drugs. Structure-based design and optimization of known MEK inhibitors resulted in identification of compound 10a as a potent non-ATP competitive MEK inhibitor in both in vitro and in vivo tests. 相似文献
4.
Flavia Varano Daniela Catarzi Matteo Falsini Fabrizio Vincenzi Silvia Pasquini Katia Varani Vittoria Colotta 《Bioorganic & medicinal chemistry》2018,26(12):3688-3695
In this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A1, A2A, A2B and A3 adenosine receptors expressed in CHO cells. The results reveal that the higher affinity of these new set of thiazolopyrimidines is toward the hA1 and hA2A adenosine receptors subtypes and is tuned by the substitution pattern at both the 2 and 5 positions of the thiazolopyrimidine nucleus. Functional studies evidenced that the compounds behaved as dual A1/A2A antagonists/inverse agonists. Compound 3, bearing a 5-((2-methoxyphenyl) methylamino) group and a phenyl moiety at position 2, displayed the highest affinity (hA1 Ki?=?10.2?nM; hA2A Ki?=?4.72?nM) and behaved as a potent A1/A2A antagonist/inverse agonist (hA1 IC50?=?13.4?nM; hA2A IC50?=?5.34?nM). 相似文献
5.
Keisuke Motoyama Tsutomu Nagata Jun Kobayashi Akifumi Nakamura Naoki Miyoshi Miho Kazui Ken Sakurai Tomoko Sakakura 《Bioorganic & medicinal chemistry letters》2018,28(12):2222-2227
In this study, we aimed to synthesize a novel blocker of transient receptor potential canonical 6 (TRPC6). The sp2 carbon atoms of the aminoindane skeleton of the known inhibitor were replaced with sp3 carbon atoms to increase the molecular complexity, measured by fraction sp3 (Fsp3). The representative compound, a bicyclo[4.3.0]nonane derivative DS88790512, inhibited TRPC6 with an IC50 value of 11?nM. Notably, DS88790512 exhibited excellent selectivity against hERG and hNaV1.5 channels, and was identified as an orally bioavailable compound. 相似文献
6.
《Bioorganic & medicinal chemistry》2016,24(21):5249-5257
In order to address the current downturn in the drug discovery pipeline, initiatives are being undertaken to synthesise screening libraries of sp3-rich, low molecular weight compounds. As part of the European Lead Factory initiative, the synthesis and derivatisation of a simple hexahydrooxazolo[5,4-c]pyridin-2(1H)-one bicyclic carbamate has been achieved. The synthetic route employed involved a telescoped hetero-Diels–Alder/[2,3]-sigmatropic rearrangement/cyclisation sequence to deliver the desired core scaffold containing two points for further diversification. When applied, this synthesis was found to be robust and scalable which allowed the production of a 155 compound library. 相似文献
7.
《Bioorganic & medicinal chemistry》2014,22(15):3862-3870
Several histone deacetylase (HDAC) inhibiting bicyclic tetrapeptides have been designed and synthesized through intramolecular ring-closing metathesis (RCM) reaction and peptide cyclization. We designed bicyclic tetrapeptides based on CHAP31, trapoxin B and HC-toxin I. The HDAC inhibitory and p21 promoter assay results showed that the aliphatic loop position as well as the hydrophobicity plays an important role toward the activity of the bicyclic tetrapeptide HDAC inhibitors. 相似文献
8.
9.
Ted Johanson Ndia Skorupa Parachin Paula Adamis Marie-F. Gorwa-Grauslund 《Journal of Molecular Catalysis .B, Enzymatic》2009,59(4):286-291
Stereoselective baker's yeast-catalysed bioreduction of bicyclo [2.2.2]octane-2,6-dione generates (1R, 4S, 6S)-6-hydroxy-bicyclo [2.2.2]octane-2-one (endo-alcohol) with high enantiomeric and diastereomeric excess. In contrast, whole cells and crude membrane fractions of Candida sp. have been reported to produce the unusual (1R, 4S, 6S)-diastereomer (exo-alcohol) as a major product. Previous in silico screening has identified seven membrane or membrane-bound reductases in C. albicans as candidates for the exo-activity. In this work, purification of the corresponding exo-reductase(s) as well as the heterologous cloning of the seven candidate genes was attempted in C. tropicalis. The overexpression of IPF4033 (AYR1) gene generated an increased exo-to-endo ratio and exo-alcohol production in whole cells and membranes of C. tropicalis. In addition, a slight increased exo-to-endo ratio was observed when overexpressing IPF4033 in S. cerevisiae, although the reduction rate and exo-to-endo ratio were several fold lower compared to those obtained with C. tropicalis. 相似文献
10.
Michael A. Wright Ian N. Taylor Michael J. Lenn David R. Kelly Jasem G. Mahdi Christopher J. Knowles 《FEMS microbiology letters》1994,116(1):67-72
Abstract The oxidation of bicyclo[3.2.0]hept-2-en-6-one and 7- endo propylbicyclo[3.2.0]hept-2-en-one was investigated using whole cells of Pseudomonas putida NCIMB 10007 and Xanthobacter autotrophicus NCIMB 10811. The bacteria demonstrated both regio- and enantioselective oxidation of the substrates. P. putida gave 'mirror image' with both substrates when the products of these oxidations were compared with cells grown on the different enantiomers of camphor. The regio- and enantioselectivity of the oxidation of the substrates by X. autotrophicus were enhanced by the 7- endo propyl substitution of bicyclo[3.2.0]hept-2-en-6-one. 相似文献