169335-50-6Relevant articles and documents
Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
Zhang, Yong-Kang,Plattner, Jacob J.,Easom, Eric E.,Jacobs, Robert T.,Guo, Denghui,Sanders, Virginia,Freund, Yvonne R.,Campo, Brice,Rosenthal, Philip J.,Bu, Wei,Gamo, Francisco-Javier,Sanz, Laura M.,Ge, Min,Li, Liang,Ding, Jie,Yang, Yin
, p. 5344 - 5354 (2015)
A series of 6-hetaryloxy benzoxaborole compounds was designed and synthesized for a structure-activity relationship (SAR) investigation to assess the changes in antimalarial activity which result from 6-aryloxy structural variation, substituent modification on the pyrazine ring, and optimization of the side chain ester group. This SAR study discovered highly potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles (9, 27-34) with IC50s = 0.2-22 nM against cultured Plasmodium falciparum W2 and 3D7 strains. Compound 9 also demonstrated excellent in vivo efficacy against P. berghei in infected mice (ED90 = 7.0 mg/kg).
CYCLOPROPYL FUSED THIAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE
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Page/Page column 302, (2016/04/20)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I): wherein variables A4, A5, A6, A8, and each of Ra, Rb, R1, R2, R3 and R7 of Formula (I), independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and 15 deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas (II) and (III), and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.
Identification of RO4597014, a glucokinase activator studied in the clinic for the treatment of type 2 diabetes
Qian, Yimin,Corbett, Wendy L.,Berthel, Steven J.,Choi, Duk Soon,Dvorozniak, Mark T.,Geng, Wanping,Gillespie, Paul,Guertin, Kevin R.,Haynes, Nancy-Ellen,Kester, Robert F.,Mennona, Francis A.,Moore, David,Racha, Jagdish,Radinov, Roumen,Sarabu, Ramakanth,Scott, Nathan R.,Grimsby, Joseph,Mallalieu, Navita L.
supporting information, p. 414 - 418 (2013/07/25)
To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.
5-SUBSTITUTED-PYRAZINE OR PYRIDINE GLUCOKINASE ACTIVATORS
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Page 116, (2010/02/07)
The present invention provides a compound according to formula (I) where the substituent designations are provided in the specification. Pharmaceutical compositions comprising a compound according to formula (I) are also provided, said compounds being glucokinase activators which are useful in the treatment of type II diabetes.
Pyrazinoic Acid Esters with Broad Spectrum in Vitro Antimycobacterial Activity
Cynamon, Michael H.,Gimi, Rayomand,Gyenes, Ferenc,Sharpe, Cindy A.,Bergmann, Kathryn E.,et al.
, p. 3902 - 3907 (2007/10/02)
A series of substituted pyrazinoic acid esters has been prepared and examined for their in vitro activity against Mycobacterium avium and Mycobacterium kansasii as well as mycobacterium tuberculosis.Modification of both the pyrazine nucleus and the ester functionality have been very successfull in expanding the activity of pyrazinamide to include M. avium and M. kansasii, organisms normally not susceptible to pyrazinamide.Several of these compounds have activities 100-1000-fold greater than that of pyrazinamide against M. tuberculosis.
