1108192-19-3Relevant articles and documents
Combined Proteomic and In Silico Target Identification Reveal a Role for 5-Lipoxygenase in Developmental Signaling Pathways
Brand, Silke,Roy, Sayantani,Schr?der, Peter,Rathmer, Bernd,Roos, Jessica,Kapoor, Shobhna,Patil, Sumersing,Pommerenke, Claudia,Maier, Thorsten,Janning, Petra,Eberth, Sonja,Steinhilber, Dieter,Schade, Dennis,Schneider, Gisbert,Kumar, Kamal,Ziegler, Slava,Waldmann, Herbert
, p. 1095 - 23,1106 (2018)
Identification and validation of the targets of bioactive small molecules identified in cell-based screening is challenging and often meets with failure, calling for the development of new methodology. We demonstrate that a combination of chemical proteom
Neuritogenic Militarinone-Inspired 4-Hydroxypyridones Target the Stress Pathway Kinase MAP4K4
Schr?der, Peter,F?rster, Tim,Kleine, Stefan,Becker, Christian,Richters, André,Ziegler, Slava,Rauh, Daniel,Kumar, Kamal,Waldmann, Herbert
, p. 12398 - 12403 (2015)
Progressive loss and impaired restoration of neuronal activity are hallmarks of neurological diseases, and new small molecules with neurotrophic activity are in high demand. The militarinone alkaloids and structurally simplified analogues with 4-hydroxy-2
Conjugated Metal-Organic Macrocycles: Synthesis, Characterization, and Electrical Conductivity
Zasada, Leo B.,Guio, Lorenzo,Kamin, Austin A.,Dhakal, Diwash,Monahan, Madison,Seidler, Gerald T.,Luscombe, Christine K.,Xiao, Dianne J.
, p. 4515 - 4521 (2022/03/18)
The dimensional reduction of solids into smaller fragments provides a route to achieve new physical properties and gain deeper insight into the extended parent structures. Here, we report the synthesis of CuTOTP-OR (TOTPn- = 2,3,6,7-tetraoxidotriphenylene), a family of copper-based macrocycles that resemble truncated fragments of the conductive two-dimensional (2D) metal-organic framework Cu3(HHTP)2 (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene). The planar metal-organic macrocycles self-assemble into ordered nanotubes with internal diameters of ~2 nm and short interlayer distances of ~3.20 ?. Strong π-πstacking interactions between macrocycles facilitate out-of-plane charge transport, and pressed pellet conductivities as high as 2(1) × 10-3 S cm-1 are observed. Peripheral alkyl functionalization enhances solution processability and enables the fabrication of thin-film field-effect transistor devices. Ambipolar charge transport is observed, suggesting that similar behavior may be operative in Cu3(HHTP)2. By coupling the attractive features of metal-organic frameworks with greater processability, these macrocycles enable facile device integration and a more nuanced understanding of out-of-plane charge transport in 2D conductive metal-organic frameworks.
Hydroxyl radical-induced oxidation of a phenolic c-linked 2′-deoxyguanosine adduct yields a reactive catechol
Witham, Aaron A.,Beach, Daniel G.,Gabryelski, Wojciech,Manderville, Richard A.
scheme or table, p. 315 - 325 (2012/06/30)
Phenolic toxins stimulate oxidative stress and generate Clinked adducts at the C8-site of 2/-deoxyguanosine (dG). We previously reported that the C-linked adduct 8-(4″-hydroxyphenyl)-dG (p-PhOH-dG) undergoes oxidation in the presence of Na2IrCl
Novel CYP17 inhibitors: Synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls
Hille, Ulrike E.,Hu, Qingzhong,Vock, Carsten,Negri, Matthias,Bartels, Marc,Mueller-Vieira, Ursula,Lauterbach, Thomas,Hartmann, Rolf W.
experimental part, p. 2765 - 2775 (2009/10/09)
Recently, the steroidal CYP17 inhibitor Abiraterone entered phase II clinical trial for the treatment of androgen-dependent prostate cancer. As 17α-hydroxylase-17,20-lyase (CYP17) catalyzes the last step in androgen biosynthesis, inhibition of this target should affect not only testicular but also adrenal androgen formation. Therefore CYP17 inhibitors should be advantageous over existing therapies, for example with GnRH analogues. However, steroidal drugs are known for side effects which are due to affinities for steroid receptors. Therefore we decided to synthesize non-steroidal compounds mimicking the natural CYP17 substrates pregnenolone and progesterone. The synthesis and biological evaluation of a series of 15 novel and highly active non-steroidal CYP17 inhibitors are reported. The compounds were prepared via Suzuki-cross-coupling, Grignard reaction and CDI-assisted SNt-reaction with imidazole and their inhibitory activity was examined with recombinant human CYP17 expressed in Escherichia coli. Promising compounds were further tested for their selectivity against the hepatic enzyme CYP3A4 and the glucocorticoid-forming enzyme CYP11B1. All compounds turned out to be potent CYP17 inhibitors. The most active compounds 7 and 8 were much more active than Ketoconazole showing activity comparable to Abiraterone (IC50 values of 90 and 52 nM vs. 72 nM). Most compounds also showed higher selectivities than Ketoconazole, but turned out to be less selective than Abiraterone. Docking studies using our CYP17 protein model were performed with selected compounds to study the interactions between the inhibitors and the amino acid residues of the active site.
Asymmetric catalysis of intramolecular cyclopropanation of 5-aryl-1-diazo-1-mesitylsulfonyl-5-hexen-2-ones
Sawada, Takashi,Nakada, Masahisa
, p. 1527 - 1532 (2007/10/03)
We have examined the catalytic asymmetric intramolecular cyclopropanation (IMCP) reactions of 5-aryl-1-diazo-1-mesitylsulfonyl-5-hexen-2-ones, and found that the substituent of the 5-aryl group dramatically changes the enantioselectivity. That is, no enantioselectivity was observed when the substituent was a methoxy group; however, enantioselectivity was moderate when the substituent was a methylenedioxy group or a tert-butyldimethylsilyloxy group, and it dramatically increased when the substituent was lacking (96% ee) or a benzoyloxy group (93% ee).