Synthesis and SAR of pyrrolotriazine-4-one based Eg5 inhibitors.

  title={Synthesis and SAR of pyrrolotriazine-4-one based Eg5 inhibitors.},
  author={Kyoung Soon Kim and Songfeng Lu and Lyndon A. M. Cornelius and Louis J Lombardo and Robert M. Borzilleri and Gretchen M. Schroeder and C. Sheng and George Charles Rovnyak and Donald Crews and Robert J. Schmidt and David K. Williams and Rajeev S. Bhide and Sarah C. Traeger and Patricia A. McDonnell and Luciano Mueller and Steven Sheriff and John A Newitt and Andrew T. Pudzianowski and Zheng Yang and Robert A. Wild and Frances Y Lee and Roberta Batorsky and J. S. Ryder and Marie Ortega-Nanos and Henry Shen and Marco M. Gottardis and Deborah L. Roussell},
  journal={Bioorganic \& medicinal chemistry letters},
  volume={16 15},
Synthetic strategies for pyrrolo[2,1-f][1,2,4]triazine: the parent moiety of antiviral drug remdesivir
This review summarizes diverse synthetic protocols for the preparation of pyrrolo[2,1- f ][1,2,4]triazine derivatives, covering literature sources from the past two decades, and identifies six distinct categories for effective representation.
Pyrrolotriazinone as an Underexplored Scaffold in Drug Discovery
This work offers an extensive review of pyrrolo[2,1-f][1,2,4]triazin-4(1H)-one and pyrro[ 1,2-d], describing their biological properties en route to drug discovery.
Structure-activity relationship of S-trityl-L-cysteine analogues as inhibitors of the human mitotic kinesin Eg5.
An initial structure-activity relationship study on a series of STLC analogues reveals the minimal skeleton necessary for Eg5 inhibition as well as indications of how to obtain more potent analogues.
Design, synthesis and evaluation of tetrahydroisoquinolines as new kinesin spindle protein inhibitors.
Nine of a series of tetrahydroisoquinolines synthesized and identified as novel kinesine spindle protein (KSP) inhibitors were more active than monastrol and exhibited excellent cell-killing activities against HepG2 cells.
Structure‐Based Design of New KSP‐Eg5 Inhibitors Assisted by a Targeted Multicomponent Reaction
An integrated multidisciplinary approach that combined structure‐based drug design, multicomponent reaction synthetic approaches and functional characterization in enzymatic and cell assays led to
Discovery of Novel Allosteric Eg5 Inhibitors Through Structure‐Based Virtual Screening
A new allosteric regulation mechanism of Eg5 is explored and a novel drug targeting site for cancer therapy is identified and identified through structure‐based virtual screening.
Pyrrolo[2,1-f][1,2,4]triazine: a promising fused heterocycle to target kinases in cancer therapy
  • Sarbjit Singh, D. Utreja, Vimal Kumar
  • Biology, Chemistry
    Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents
  • 2021
This review articles focus on the recent advances made in the development of kinase inhibitors containing pyrrolo[2,1-f][1,2,4]triazine scaffold.
CPUYJ039, a newly synthesized benzimidazole‐based compound, is proved to be a novel inducer of apoptosis in HCT116 cells with potent KSP inhibitory activity
Objectives  This study investigated the antiproliferative and apoptotic activities of CPUYJ039, a newly synthesized benzimidazole‐based kinesin spindle protein (KSP) inhibitor, on HCT116 cell lines.


20th‐Century Advances in Drug Therapy in Oncology—Part I
Part II of this series discusses agents which target the mitotic mechanism by inhibiting microtubules and topoisomerase I inhibitors, which are among the most important anticancer agents currently available.
Targeting the kinesin Eg5 to monitor siRNA transfection in mammalian cells.
A single siRNA leading to an easily assayed phenotype can be used to monitor the transfection of siRNA into any type of proliferating cells of both human and murine origin, and the optimal parameters for the electroporation of si RNA differ from those for plasmids, allowing the use of milder conditions that induce less cell toxicity.
Chemotherapy-induced peripheral neuropathy
A general predisposition for developing a chemotherapy-induced neuropathy has been observed in nerves previously damaged by diabetes mellitus, alcohol or inherited neuropathy and no drug is available to reliably prevent or cure chemotherapy- induced neuropathy.
Modulation of microtubule dynamics by drugs: a paradigm for the actions of cellular regulators.
It is clear that molecules that regulate dynamics such as Kin 1 and stathmin could bind to a large number of distinct tubulin sites on microtubules and employ an array of mechanisms to selectively and powerfully regulate microtubule dynamics and dynamics-dependent cellular functions.
Automated 1H and 13C chemical shift prediction using the BioMagResBank
It is believed that SHIFTY may have widespread utility in assigning individual members in families of related proteins, an endeavor that accounts for a growing portion of the protein NMR work being done today.
Mitotic spindle organization by a plus-end-directed microtubule motor
An in vitro assay for spindle assembly, derived from Xenopus egg extracts, is used to investigate the role of Eg5, a kinesin-like protein in Xenopus eggs, and demonstrates that Eg5 is a plus-end-directed microtubule motor in vitro.