1042159-60-3Relevant articles and documents
Discovery of Novel Indoline Cholesterol Ester Transfer Protein Inhibitors (CETP) through a Structure-Guided Approach
Wilson, Jonathan E.,Kurukulasuriya, Ravi,Reibarkh, Mikhail,Reiter, Maud,Zwicker, Aaron,Zhao, Kake,Zhang, Fengqi,Anand, Rajan,Colandrea, Vincent J.,Cumiskey, Anne-Marie,Crespo, Alejandro,Duffy, Ruth A.,Murphy, Beth Ann,Mitra, Kaushik,Johns, Douglas G.,Duffy, Joseph L.,Vachal, Petr
, p. 261 - 265 (2016)
Using the collective body of known (CETP) inhibitors as inspiration for design, a structurally novel series of tetrahydroquinoxaline CETP inhibitors were discovered. An exemplar from this series, compound 5, displayed potent in vitro CETP inhibition and was efficacious in a transgenic cynomologus-CETP mouse HDL PD (pharmacodynamic) assay. However, an undesirable metabolic profile and chemical instability hampered further development of the series. A three-dimensional structure of tetrahydroquinoxaline inhibitor 6 was proposed from 1H NMR structural studies, and this model was then used in silico for the design of a new class of compounds based upon an indoline scaffold. This work resulted in the discovery of compound 7, which displayed potent in vitro CETP inhibition, a favorable PK-PD profile relative to tetrahydroquinoxaline 5, and dose-dependent efficacy in the transgenic cynomologus-CETP mouse HDL PD assay.
Orthogonal Pd- and Cu-based catalyst systems for C- and N-arylation of oxindoles
Altman, Ryan A.,Hyde, Alan M.,Huang, Xiaohua,Buchwald, Stephen L.
supporting information; scheme or table, p. 9613 - 9620 (2009/02/02)
In the cross-coupling reactions of unprotected oxindoles with aryl halides, Pd- and Cu-based catalyst systems displayed orthogonal chemoselectivity. A Pd-dialkylbiarylphosphine-based catalyst system chemoselectively arylated oxindole at the 3 position, while arylation occurred exclusively at the nitrogen using a Cu-diamine-based catalyst system. Computational examination of the relevant L1Pd(Ar)(oxindolate) and diamine-Cu(oxindolate) species was performed to gain mechanistic insight into the controlling features of the observed chemoselectivity.