1350374-46-7Relevant articles and documents
Nonclassical Phenyl Bioisosteres as Effective Replacements in a Series of Novel Open-Source Antimalarials
Tse, Edwin G.,Houston, Sevan D.,Williams, Craig M.,Savage, G. Paul,Rendina, Louis M.,Hallyburton, Irene,Anderson, Mark,Sharma, Raman,Walker, Gregory S.,Obach, R. Scott,Todd, Matthew H.
, p. 11585 - 11601 (2020/12/04)
The replacement of one chemical motif with another that is broadly similar is a common method in medicinal chemistry to modulate the physical and biological properties of a molecule (i.e., bioisosterism). In recent years, bioisosteres such as cubane and bicyclo[1.1.1]pentane (BCP) have been used as highly effective phenyl mimics. Herein, we show the successful incorporation of a range of phenyl bioisosteres during the open-source optimization of an antimalarial series. Cubane (19) and closo-carborane (23) analogues exhibited improved in vitro potency against Plasmodium falciparum compared to the parent phenyl compound; however, these changes resulted in a reduction in metabolic stability; unusually, enzyme-mediated oxidation was found to take place on the cubane core. A BCP analogue (22) was found to be equipotent to its parent phenyl compound and showed significantly improved metabolic properties. While these results demonstrate the utility of these atypical bioisosteres when used in a medicinal chemistry program, the search to find a suitable bioisostere may well require the preparation of many candidates, in our case, 32 compounds.
Synthesis and structure-activity relationship of p-carborane-based non-secosteroidal vitamin D analogs
Fujii, Shinya,Kano, Atsushi,Songkram, Chalermkiat,Masuno, Hiroyuki,Taoda, Yoshiyuki,Kawachi, Emiko,Hirano, Tomoya,Tanatani, Aya,Kagechika, Hiroyuki
, p. 1227 - 1235 (2014/03/21)
1α,25-Dihydroxyvitamin D3 [1α,25(OH) 2D3: 1] is a specific modulator of nuclear vitamin D receptor (VDR), and novel vitamin D analogs are therapeutic candidates for multiple clinical applications. We recently developed non
Boron cluster-based development of potent nonsecosteroidal vitamin D receptor ligands: Direct observation of hydrophobic interaction between protein surface and carborane
Fujii, Shinya,Masuno, Hiroyuki,Taoda, Yoshiyuki,Kano, Atsushi,Wongmayura, Angsuma,et al.
, p. 20933 - 20941 (2012/03/07)
We report here the design and synthesis of a novel vitamin D receptor (VDR) agonist whose hydrophobic core structure is p-carborane (1,12-dicarba-closo- dodecaborane, an icosahedral carbon-containing boron cluster having remarkable thermal and chemical st
