105147-86-2Relevant academic research and scientific papers
SYNTHESIS OF NEW DEAZAFLAVINS WITH PLANAR CHIRALITY. REDOX-INDUCED "ROPE-SKIPPING" RACEMIZATION
Shinkai, Seiji,Yamaguchi, Toshiro,Nakao, Hideki,Manabe, Osamu
, p. 1611 - 1614 (1986)
New 5-deazaflavins with planar chirality (dF1(n)) were synthesized in which N(3) and O(2'α) in the 10-(2'-hydroxy)phenyl group were linked by a -(CH2)- chain (n=8,10). (+)-dF1(n=8) showed a large chiral discrimination in fluorescence quenching
Toxoflavins and deazaflavins as the first reported selective small molecule inhibitors of tyrosyl-DNA phosphodiesterase II
Raoof, Ali,Depledge, Paul,Hamilton, Niall M.,Hamilton, Nicola S.,Hitchin, James R.,Hopkins, Gemma V.,Jordan, Allan M.,Maguire, Laura A.,McGonagle, Alison E.,Mould, Daniel P.,Rushbrooke, Mathew,Small, Helen F.,Smith, Kate M.,Thomson, Graeme J.,Turlais, Fabrice,Waddell, Ian D.,Waszkowycz, Bohdan,Watson, Amanda J.,Ogilvie, Donald J.
supporting information, p. 6352 - 6370 (2013/09/23)
The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAR) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.
Coenzyme Models. 47. Synthesis and Reactivity Studies of Novel Flavinophanes and 5-Deazaflavinophanes: Correlation between Flavin Reactivity and Ring Strain
Shinkai, Seiji,Kawase, Akito,Yamaguchi, Toshiro,Manabe, Osamu,Wada, Yoshikazu,et al.
, p. 4928 - 4935 (2007/10/02)
New flavinophanes Fl(n) and 5-deazaflavinophanes dFl(n) were synthesized in which N(3) and O(2') in the 10-(2-hydroxyphenyl) group were linked by a -(CH2)n- chain (n = 6, 7, 8, 10, and 12).In the (1)H NMR spectra the chemical shift of 9-H in the isoalloxa
