Tomonobu Umetani

Bio: Tomonobu Umetani is an academic researcher from Takeda Pharmaceutical Company. The author has contributed to research in topics: Benzopyran & Carboxylic acid. The author has an hindex of 3, co-authored 6 publications receiving 293 citations.

Chromone: A Valid Scaffold in Medicinal Chemistry

Abstract: This work was supported by the Foundation for Science and Technology (FCT), Portugal (projects PTDC/QUI-QUI/113687/2009 and PEst-C/QUI/UI0081/2013). A.G. (SFRH/BD/43531/2008) and M.J.M. (SFRH/BD/61262/2009) thank FCT for grants.

Medicinal chemistry of tetrazoles.

Abstract: Publisher Summary Tetrazole itself exhibits no pharmacological activity; however, many of its derivatives possess interesting biological actions. The tetrazole function is metabolically stable and this feature and a close similarity between the acidic character of the tetrazole group and the carboxylic group have inspired syntheses of potential medicinal agents. This chapter discusses the literature on the medicinal chemistry of tetrazoles. The most successful drug among the CNS acting tetrazole derivatives has been leptazol. The tetrazole system is metabolically stable and it may be of interest to introduce this stable lump on biologically active moieties and examine the effect produced on the activity. There are several instances of introduction of tetrazole heterocycle in the synthesis of new medicinal agents. A particular mention has been made of the promising anti-bacterial cephalosporin derivatives cephazolin sodium, ceftezole, and cephamandole.

Identification of a Potent and Selective Pharmacophore for Cdc25 Dual Specificity Phosphatase Inhibitors.

Abstract: Small molecules provide powerful tools to interrogate biological pathways but many important pathway participants remain refractory to inhibitors. For example, Cdc25 dual-specificity phosphatases regulate mammalian cell cycle progression and are implicated in oncogenesis, but potent and selective inhibitors are lacking for this enzyme class. Thus, we evaluated 10,070 compounds in a publicly available chemical repository of the National Cancer Institute for in vitro inhibitory activity against oncogenic, full-length, recombinant human Cdc25B. Twenty-one compounds had mean inhibitory concentrations of 75% were quinones and >40% were of the para-naphthoquinone structural type. Most notable was NSC 95397 (2,3-bis-[2-hydroxyethylsulfanyl]-[1,4]naphthoquinone), which displayed mixed inhibition kinetics with in vitro K(i) values for Cdc25A, -B, and -C of 32, 96, and 40 nM, respectively. NSC 95397 was more potent than any inhibitor of dual specificity phosphatases described previously and 125- to 180-fold more selective for Cdc25A than VH1-related dual-specificity phosphatase or protein tyrosine phosphatase 1b, respectively. Modification of the bis-thioethanol moiety markedly decreased enzyme inhibitory activity, indicating its importance for bioactivity. NSC 95397 showed significant growth inhibition against human and murine carcinoma cells and blocked G(2)/M phase transition. A potential Cdc25 site of interaction was postulated based on molecular modeling with these quinones. We propose that inhibitors based on this chemical structure could serve as useful tools to probe the biological function of Cdc25.