108732-34-9Relevant academic research and scientific papers
Identification of an anti-inflammatory derivative with anti-cancer potential: The impact of each of its structural components on inflammatory responses in macrophages and bladder cancer cells
Hamelin-Morrissette, Jovane,Cloutier, Suzie,Girouard, Julie,Belgorosky, Denise,Eiján, Ana María,Legault, Jean,Reyes-Moreno, Carlos,Bérubé, Gervais
, p. 259 - 268 (2015)
Inflammation plays a crucial role in many types of cancer and is known to be involved in their initiation and promotion. As such, it is presently recognized as an important risk factor for several types of cancers such as bladder, prostate and breast cancers. The discovery of novel anti-inflammatory compounds can have a huge implication not only for the treatment of cancer but also as preventive and protective treatment modalities. We have recently identified a new compound (1) that presents interesting anti-inflammatory activity. In order to better understand its biological action, we have divided the molecule in its basic components and verified their respective contribution towards the anti-inflammatory response of the whole molecule. We have discovered that only the combination of the maleimide function together with the tert-butyloxycarbonylhydrazinamide function lead to important anti-inflammatory properties. The main derivative 1 can decrease the activating effects of INFγ or IL6 on human (hMωs) macrophages by 38% or by 64% at a concentration of 10 μM as indicated by a decrease of STAT1 or STAT3 activation. The expression of pro-inflammatory markers CD40 and MHCII in INFγ stimulated hMωs were reduced by 87% and 49%, respectively with a 3 h pretreatment of 1 at 10 μM. The cell motility assay revealed that 1 at 10 μM can reduce relative cell motility induced by IL6 by 92% in comparison with the untreated control hMω monolayers. Compound 1 reduced by 91% the inflammatory response induced by the cytokines (INFγ + TNFα) in the macrophage-like J774A.1 cells at a concentration of 25 μM, as measured by the detection of NO production with the Griess reagent. Furthermore, upon removal of the tert-butyloxycarbonyl protective group the unprotected derivative as a hydrochloride salt (1A) retains interesting anti-inflammatory activity and was found to be less toxic than the parent compound (1).
Catalyst control over regio- and enantioselectivity in baeyer-villiger oxidations of functionalized ketones
Romney, David K.,Colvin, Sean M.,Miller, Scott J.
, p. 14019 - 14022 (2014)
We report a peptide-based catalyst that can strongly influence the regio- and enantioselectivity of the Baeyer-Villiger (BV) oxidation of cyclic ketones bearing amide, urea, or sulfonamide functional groups. Both types of selectivity are thought to arise from a catalyst-substrate hydrogen-bonding interaction. Furthermore, in selected cases, the reactions exhibit the hallmarks of parallel kinetic resolution. The capacity to use catalysis to select between BV products during an asymmetric process may have broad utility for both the synthesis and diversification of complex molecules, including natural products.
Discovery, synthesis, and biological evaluation of a novel group of selective inhibitors of filoviral entry
Yermolina, Maria V.,Wang, Jizhen,Caffrey, Michael,Rong, Lijun L.,Wardrop, Duncan J.
experimental part, p. 765 - 781 (2011/04/15)
Herein, we report the development of an antifiloviral screening system, based on a pseudotyping strategy, and its application in the discovery of a novel group of small molecules that selectively inhibit the Ebola and Marburg glycoprotein (GP)-mediated infection of human cells. Using Ebola Zaire GP-pseudotyped HIV particles bearing a luciferase reporter gene and 293T cells, a library of 237 small molecules was screened for inhibition of GP-mediated viral entry. From this assay, lead compound 8a was identified as a selective inhibitor of filoviral entry with an IC50 of 30 μM. To analyze functional group requirements for efficacy, a structure-activity relationship analysis of this 3,5-disubstituted isoxazole was then conducted with 56 isoxazole and triazole derivatives prepared using "click" chemistry. This study revealed that while the isoxazole ring can be replaced by a triazole system, the 5-(diethylamino)acetamido substituent found in 8a is required for inhibition of viral-cell entry. Variation of the 3-aryl substituent provided a number of more potent antiviral agents with IC50 values ranging to 2.5 μM. Lead compound 8a and three of its derivatives were also found to block the Marburg glycoprotein (GP)-mediated infection of human cells.
An improved procedure for the preparation of 8-substituted guanines
Xu, Ming,De Giacomo, Fabio,Paterson, Duncan E.,George, Tesmol G.,Vasella, Andrea
, p. 1452 - 1453 (2007/10/03)
The preparation of 8-substituted guanines using a new phosphorus(III)-mediated cyclisation of 4-acylamino-5-nitrosopyrimidines as the key step is described.
PHASE MANAGED ORGANIC SYNTHESIS 2. A NEW POLYMER ASSISTED SYNTHESIS OF ACID ANHYDRIDES.
Fife, Wilmer K.,Zhang, Zhi-dong
, p. 4933 - 4936 (2007/10/02)
A solid-phase copolymer of 4-vinylpyridine is shown to be a highly effective reagent/catalyst for the synthesis of acid anhydrides from mixtures containing equimolar quantities of carboxylic acid and acid chlorides.The process may be carried out in batch or column mode.
