857035-61-1Relevant articles and documents
β-Amino alcohols from anilines and ethylene glycol through heterogeneous Borrowing Hydrogen reaction
Llabres-Campaner, Pedro J.,Ballesteros-Garrido, Rafael,Ballesteros, Rafael,Abarca, Belén
supporting information, p. 5552 - 5561 (2017/08/22)
Borrowing Hydrogen (BH), also called Hydrogen Autotransfer (HA), reaction with neat ethylene glycol represents a key step in the preparation of β-amino alcohols. However, due to the stability of ethylene glycol, mono-activation has rarely been achieved. Herein, a combination of Pd/C and ZnO is reported as heterogeneous catalyst for this BH/HA reaction. This system results in an extremely air and moisture stable, and economic catalyst able to mono-functionalize ethylene glycol in water, without further activation of the diol. In this work, different diols and aromatic amines have been explored affording a new approach towards amino alcohols. This study reveals how the combination of two solid species can afford interesting catalytic properties in heterogeneous phase. ZnO activates ethylene glycol while Pd/C is the responsible of the BH/HA cycle. This catalytic system has also been found useful to dehydrogenate indoles affording indolines that undergo in situ BH/HA cycle prior to re-aromatization, representing a tandem heterogeneous process.
Searching for New Leads for Tuberculosis: Design, Synthesis, and Biological Evaluation of Novel 2-Quinolin-4-yloxyacetamides
Pitta, Eleni,Rogacki, Maciej K.,Balabon, Olga,Huss, Sophie,Cunningham, Fraser,Lopez-Roman, Eva Maria,Joossens, Jurgen,Augustyns, Koen,Ballell, Lluis,Bates, Robert H.,Van Der Veken, Pieter
, p. 6709 - 6728 (2016/08/05)
In this study, a new series of more than 60 quinoline derivatives has been synthesized and evaluated against Mycobacterium tuberculosis (H37Rv). Apart from the SAR exploration around the initial hits, the optimization process focused on the improvement of the physicochemical properties, cytotoxicity, and metabolic stability of the series. The best compounds obtained exhibited MIC values in the low micromolar range, excellent intracellular antimycobacterial activity, and an improved physicochemical profile without cytotoxic effects. Further investigation revealed that the amide bond was the source for the poor blood stability observed, while some of the compounds exhibited hERG affinity. Compound 83 which contains a benzoxazole ring instead of the amide group was found to be a good alternative, with good blood stability and no hERG affinity, providing new opportunities for the series. Overall, the obtained results suggest that further optimization of solubility and microsomal stability of the series could provide a strong lead for a new anti-TB drug development program.
Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121)
Bonfanti, Jean-Fran?ois,Meyer, Christophe,Doublet, Frédéric,Fortin, Jér?me,Müller, Philippe,Queguiner, Laurence,Gevers, Tom,Janssens, Peggy,Szel, Heidi,Willebrords, Rudy,Timmerman, Philip,Wuyts, Koen,Van Remoortere, Pieter,Janssens, Frans,Wigerinck, Piet,Andries, Koen
, p. 875 - 896 (2008/09/19)
A preceding paper (Bonfanti et al. J. Med Chem. 2007, 50, 4572-4584) reported the optimization of the pharmacokinetic profile of substituted benzimidazoles by reducing their tissue retention. However, the modifications that were necessary to achieve this goal also led to a significant drop in anti-RSV activity. This paper describes a molecular modeling study followed by a lead optimization program that led to the recovery of the initial potent antiviral activity and the selection of TMC353121 as a clinical candidate.
