39799-70-7Relevant academic research and scientific papers
Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis
Heimburg, Tino,Chakrabarti, Alokta,Lancelot, Julien,Marek, Martin,Melesina, Jelena,Hauser, Alexander-Thomas,Shaik, Tajith B.,Duclaud, Sylvie,Robaa, Dina,Erdmann, Frank,Schmidt, Matthias,Romier, Christophe,Pierce, Raymond J.,Jung, Manfred,Sippl, Wolfgang
, p. 2423 - 2435 (2016/04/10)
Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (1 and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.
Highly ortho-Selective Chlorination of Anilines Using a Secondary Ammonium Salt Organocatalyst
Xiong, Xiaodong,Yeung, Ying-Yeung
supporting information, p. 16101 - 16105 (2016/12/26)
An organocatalytic, highly facile, efficient, and regioselective ortho-chlorination of anilines is described. A secondary ammonium chloride salt has been employed as the catalyst and the reaction can be conducted at room temperature without protection from air and moisture. In addition, the reaction is readily scalable and the catalyst can be recycled and reused. This catalytic protocol has been applied to the efficient synthesis of a highly potent c-Met kinase inhibitor. Mechanistic studies revealed that unique structural features of the secondary ammonium chloride salt are important for both the catalysis and regioselectivity of the electrophilic ortho-chlorination.
PHARMACEUTICAL COMPOSITION FOR INHIBITING THE TRANSCRIPTION FACTOR INDUCIBLE BY HYPOXIA, MODULATORS OF PATHOLOGICAL PROCESSES OF ANGIOGENESIS, ONCOGENESIS, INFLAMMATION, APOPTOSIS, AND CELLULAR THERAPY
-
Page/Page column 21, (2011/04/18)
The present invention is included in the field of pharmacology and medical chemistry and relates to novel molecules represented by general formula (I), especially the one called FM19G11, as well as to pharmaceutical compositions containing them. Said pharmacologically optimized compositions are capable of modulating and/or inhibiting the transcription of genes modulated by the hypoxia-inducible transcription factor (HIF) and which are directly and/or indirectly involved in pathological processes related to cancer, inflammation, tissue repair, stem cell differentiation and regenerative therapy. The present invention also relates to a method for the synthesis of said molecules (I) and to the use thereof in the manufacture of a medicament for the treatment of the mentioned pathological processes.
Palladium-catalyzed silane/siloxane reductions in the one-pot conversion of nitro compounds into their amines, hydroxylamines, amides, sulfonamides, and carbamates
Rahaim Jr., Ronald J.,Maleczka Jr., Robert E.
, p. 3316 - 3340 (2008/09/17)
A combination of palladium(II) acetate, aqueous potassium fluoride, and polymethylhydrosiloxane (PMHS) facilitates the room-temperature reduction of aromatic nitro compounds to anilines. These reactions tend to be quick (30 min), high-yielding, and tolerate a range of other functional groups. Replacement of PMHS/KF with triethylsilane allows for the reduction of aliphatic nitro compounds to their corresponding hydroxylamines. Depending on the substrate, both conditions can allow for the in situ conversion of the product amines into amides, sulfonamides, and carbamates. Georg Thieme Verlag Stuttgart.
Palladium-catalyzed intermolecular coupling of aryl halides and amides
Yin, Jingjun,Buchwald, Stephen L.
, p. 1101 - 1104 (2007/10/03)
The first general intermolecular C-N bond-forming reactions between aryl halides and amides were realized using a palladium catalyst with Xantphos as the ligand. Aryl triflates, carbamates, and sulfonamides are also viable substrates for the amidations, which proceed at 45-110 °C with 1-4 mol% of Pd catalyst in 66-99% yields and exhibit good functional group compatibility.
JOINT EFFECT OF STRUCTURE OF REAGENTS AND TEMPERATURE ON REACTIVITY OF AROYL BROMIDE-PRIMARY ARYLAMINE SYSTEMS IN BENZENE. CROSSED CORRELATION
Shpan'ko, I. V.,Goncharov, A. N.,Likhomanenko, E. E.
, p. 522 - 530 (2007/10/02)
The kinetics of the reactions of aroyl bromides with primary arylamines in benzene were studied at 10, 25, 40, and 55 deg C.The effects of factors (temperature, the structure of the aroyl bromides and primary arylamines) varied separately and in pairs and also the joint effect of the three factors on the process rate were assessed quantitatively.The joint effect of the structure of the primary arylamines and the temperature on the reactivity of the system is nonadditive, and the effect of the structure of the aroyl bromides and temperature is additive.The influence of the varied parameters on the nature of the translation states in the reactions is discussed.
JOINT EFFECT OF THE STRUCTURE OF THE REAGENTS AND THE POLARITY OF THE MEDIUM ON THE RATE OF REACTIONS OF AROYL CHLORIDES WITH PRIMARY ARYLAMINES. CROSSED CORRELATION
Shpan'ko, I. V.,Likhomanenko, E. E.,Litvinenko, L. M.,Goncharov, A. N.
, p. 1390 - 1397 (2007/10/02)
The kinetics of the reactions of aroyl chlorides with primary arylamines in volume mixtures of chlorobenzene with nitrobenzene were studied with crossed variation in the structures of the reagents.The effect of various factors (the structure of the primary arylamines, the structure of the aroyl chlorides, the polarity of the medium), varied separately and in pairs, and also the joint effect of the three factors on the process rate were assessed.It was found that the structure of the reagents and the polarity of the medium have a nonadditive type of mutual effect on the reactivity of the aroyl chloride-primary arylamine system.The influence of the varied factors on the nature of the transition states in the reactions is discussed.
