24243-01-4Relevant academic research and scientific papers
HETEROCYCLIC MITOCHONDRIAL ACTIVITY INHIBITORS AND USES THEREOF
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, (2019/05/22)
Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (A/K), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.
Deacetylcolchicine deriv.
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, (2016/10/08)
Provided are 4-modified colchicine compounds and medicines using the same. Specifically provided are colchicine derivatives represented by general formula (1), salts thereof, and solvates of the same. In general formula (1), R1 is a halogen atom, a hydroxyl group, a nitro group, an amino group, or a mono-, di- or tri-fluoromethyl group; R2, R3 and R4 are each a methoxy group or a hydroxyl group, or alternatively R2 and R3, or R3 and R4 together represent a methylenedioxy group; R5 and R6 may be the same or different and are each a hydrogen atom, a C1-6 alkyl group, an arylalkyl group, a C2-6 alkenyl group, -COR7, -COOR8, -SO2R9, -CONR10R11, or -CSNR12R13, or alternatively R5 and R6 together with the nitrogen atom to which R5 and R6 are bonded may form a three- to seven-membered cyclic amino group; R7 is a C1-6 alkyl group or the like; R8 is a C1-6 alkyl group or the like; R9 is a C1-6 alkyl group or the like; R10 and R11 may be the same or different and are each a hydrogen atom, a C1-6 alkyl group, or the like; and R12 and R13 may be the same or different and are each a hydrogen atom, an alkyl group, or the like.
DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
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, (2013/04/10)
The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.
DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
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, (2013/04/13)
The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.
An inhibitor of glutathione S-transferase omega 1 that selectively targets apoptotic cells
Pace, Nicholas J.,Pimental, Daniel R.,Weerapana, Eranthie
, p. 8365 - 8368 (2012/09/25)
On (cell) suicide watch: The increased permeability of apoptotic cells was used to identify a peptide-based, covalent inhibitor (NJP2) for glutathione S-transferase omega (GSTO1) that is highly selective for apoptotic cells, with no inhibition of healthy
New Antibacterial Agents Derived from the DNA Gyrase Inhibitor Cyclothialidine
Angehrn, Peter,Buchmann, Stefan,Funk, Christoph,Goetschi, Erwin,Gmuender, Hans,Hebeisen, Paul,Kostrewa, Dirk,Link, Helmut,Luebbers, Thomas,Masciadri, Raffaello,Nielsen, Joergen,Reindl, Peter,Ricklin, Fabienne,Schmitt-Hoffmann, Anne,Theil, Frank-Peter
, p. 1487 - 1513 (2007/10/03)
Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products. It acts by competitively inhibiting the ATPase activity exerted by the B subunit of DNA gyrase but barely exhibits any growth inhibitory activity against intact bacterial cells, presumably due to insufficient permeation of the cytoplasmic membrane. To explore the antibacterial potential of 1, we developed a flexible synthetic route allowing for the systematic modification of its structure. From a first set of analogues, structure-activity relationships (SAR) were established for different substitution patterns, and the 14-hydroxylated, bicyclic core (X) of 1 seemed to be the structural prerequisite for DNA gyrase inhibitory activity. The variation of the lactone ring size, however, revealed that activity can be found among 11- to 16-membered lactones, and even seco-analogues were shown to maintain some enzyme inhibitory properties, thereby reducing the minimal structural requirements to a rather simple, hydroxylated benzyl sulfide (XI). On the basis of these "minimal structures" a modification program afforded a number of inhibitors that showed in vitro activity against Gram-positive bacteria. The best activities were displayed by 14-membered lactones, and representatives of this subclass exhibit excellent and broad in vitro antibacterial activity against Gram-positive pathogens, including Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, and overcome resistance against clinically used drugs. By improving the pharmacokinetic properties of the most active compounds (94, 97), in particular by lowering their lipophilic properties, we were able to identify congeners of cyclothialidine (1) that showed efficacy in vivo.
DNA gyrase inhibitors and pharmaceutical preparations therefor
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, (2008/06/13)
Bicyclic derivatives of the formula STR1 wherein X1, X2, R1, R2, R3, R4, R5, R6, R7a, R7b, and R8 are as defined in the specification. These compounds are antimicrobially active.
