167757-45-1Relevant articles and documents
Synthesis of Nitriles from Aldoximes and Primary Amides Using XtalFluor-E
Keita, Massaba,Vandamme, Mathilde,Paquin, Jean-Fran?ois
, p. 3758 - 3766 (2015/11/28)
The dehydration reaction of aldoximes and amides for the synthesis of nitriles using [Et2NSF2]BF4 (XtalFluor-E) is described. Overall, the reaction proceeds rapidly (normally 1 h) at room temperature in an environmentally benign solvent (EtOAc) with only a slight excess of the dehydrating agent (1.1 equiv). A broad scope of nitriles can be prepared, including chiral nonracemic ones. In addition, in a number of cases, further purification of the nitrile after the workup was not required.
Optimization of diarylthiazole B-Raf inhibitors: Identification of a compound endowed with high oral antitumor activity, mitigated hERG inhibition, and low paradoxical effect
Pulici,Traquandi,Marchionni,Modugno,Lupi,Amboldi,Casale,Colombo,Corti,Fasolini,Gasparri,Pastori,Scolaro,Donati,Felder,Galvani,Isacchi,Pesenti,Ciomei
, p. 276 - 295 (2015/02/05)
Aberrant activation of the mitogen-activated protein kinase (MAPK)-mediated pathway components, RAF-MEK-ERK, is frequently observed in human cancers and clearly contributes to oncogenesis. As part of a project aimed at finding inhibitors of B-Raf, a key player in the MAPK cascade, we originally identified a thiazole derivative endowed with high potency and selectivity, optimal in vitro ADME properties, and good pharmacokinetic profiles in rodents, but that suffers from elevated hERG inhibitory activity. An optimization program was thus undertaken, focused mainly on the elaboration of the R1 and R2 groups of the scaffold. This effort ultimately led to N-(4-{2-(1-cyclopropylpiperidin-4-yl)-4-[3-(2,5-difluorobenzenesulfonylamino)-2-fluorophenyl]thiazol-5-yl}-pyridin-2-yl)acetamide (20), which maintains favorable in vitro and in vivo properties, but lacks hERG liability. Besides exhibiting potent antiproliferative activity against only cell lines bearing B-Raf V600E or V600D mutations, compound 20 also intriguingly shows a weaker "paradoxical" activation of MEK in non-mutant B-Raf cells than other known B-Raf inhibitors. It also demonstrates very good efficacy in vivo against the A375 xenograft melanoma model (tumor volume inhibition >90% at 10 mg kg-1); it is therefore a suitable candidate for preclinical development.
THIAZOLYLPHENYL-BENZENESULFONAMIDO DERIVATIVES AS KINASE INHIBITORS
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Paragraph 0314; 0315; 0316; 0317, (2014/01/07)
Thiazolylphenyl-benzenesulfonamido derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.
THIAZOLYLPHENYL-BENZENESULFONAMIDO DERIVATIVES AS KINASE INHIBITORS
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Page/Page column 40-41, (2012/09/11)
Thiazolylphenyl-benzenesulfonamido derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.
PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
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, (2008/06/13)
The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
Amidine compounds
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, (2008/06/13)
A compound of the formula [I] wherein R1, R2and R3are the same or different and each is hydrogen atom, wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof. The compound of the presen
5-membered heterocycles, medicaments containing these compounds, their use and processes for their preparation
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, (2008/06/13)
5-Membered heterocyclic compounds, of which the following compounds are exemplary: (a) 4-??trans-4-(2-carboxyethyl)cyclohexyl!aminocarbonyl!-1-(4-piperidyl)imidazole, (b) 5-??trans-4-(2-carboxyethyl)cyclohexyl!aminocarbonyl!-4-methyl-2-(4-piperidyl)-1,3-thiazole, (c) 5-??4-(carboxymethoxy)phenyl!aminocarbonyl!-4-methyl-2-(4-piperidyl)-1,3-thiazole, (d) 5-??trans-4-(2-carboxyethyl)cyclohexyl!aminocarbonyl!-2-(4-piperidyl)-1,3,4-thiadiazole, (e) 5-??4-(carboxymethoxy)phenyl!aminocarbonyl!-2-(4-piperidyl)-1,3,4-thiadiazole, (f) 5-??trans-4-(carboxymethoxy)cyclohexyl!aminocarbonyl!-2-(4-piperidyl)-1,3-thiazole, (g) 5-??4-(carboxymethoxy)phenyl!aminocarbonyl!-2-(4-piperidyl)-1,3-thiazole, (h) 5-??trans-4-(2-carboxyethyl)cyclohexyl!aminocarbonyl!-2-(4-piperidyl)-1,3-thiazole, and (i) 4-??trans-4-carboxycyclohexyl!aminocarbonyl!-1-?2-(4-piperidyl)ethyl!imidazole. These are useful for the treatment or prevention of illnesses in which relatively small or relatively large cell aggregates occur or cell-matrix interactions play a part.
Bicyclic heterocyclic compounds, pharmaceutical preparations containing these compounds and processes for their preparations
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, (2008/06/13)
The invention relates to bicyclic heterocyclic compounds of general formula STR1 wherein A to F, Y1 and Y2 are defined as in claim 1, the tautomers thereof, the stereoisomers thereof including their mixtures, and salts thereof, parti
