63909-28-4Relevant articles and documents
Tetrahydroisoquinolinone-based steroidomimetic and chimeric microtubule disruptors
Leese, Mathew P.,Jourdan, Fabrice L.,Major, Meriel R.,Dohle, Wolfgang,Hamel, Ernest,Ferrandis, Eric,Fiore, Ann,Kasprzyk, Philip G.,Potter, Barry V. L.
, p. 85 - 108 (2014/01/17)
A structure-activity relationship (SAR) translation strategy was used for the discovery of tetrahydroisoquinoline (THIQ)-based steroidomimetic and chimeric microtubule disruptors based upon a steroidal starting point. A steroid A,B-ring-mimicking THIQ core was connected to methoxyaryl D-ring ring mimics through methylene, carbonyl and sulfonyl linkers to afford a number of steroidomimetic hits (e.g., 7-methoxy-2-(3- methoxybenzyl)-6-sulfamoyloxy-1,2,3, 4-tetrahydroisoquinoline (20 c) GI50=2.1 μM). Optimisation and control experiments demonstrate the complementary SAR of this series and the steroid derivatives that inspired its design. Linkage of the THIQ-based A,B-mimic with the trimethoxyaryl motif prevalent in colchicine site binding microtubule disruptors delivered a series of chimeric molecules whose activity (GI50=40 nM) surpasses that of the parent steroid derivatives. Validation of this strategy was obtained from the excellent oral activity of 7-methoxy-6-sulfamoyloxy-2-(3,4,5-trimethoxybenzyl)-1,2,3,4- tetrahydroisoquinoline (20 z) relative to a benchmark steroidal bis- sulfamate Copyright
Synthesis and biological evaluation of berberine analogues as novel up-regulators for both low-density-lipoprotein receptor and insulin receptor
Wang, Yan-Xiang,Wang, Yu-Ping,Zhang, Hao,Kong, Wei-Jia,Li, Ying-Hong,Liu, Fei,Gao, Rong-Mei,Liu, Ting,Jiang, Jian-Dong,Song, Dan-Qing
scheme or table, p. 6004 - 6008 (2010/06/16)
Berberine (BBR) is a natural compound with up-regulating activity on both low-density-lipoprotein receptor (LDLR) and insulin receptor (InsR). This one-drug-multiple-target characteristic might be suitable for the treatment of metabolic syndrome. In searching for up-regulators effective for both LDLR and InsR expression, the structure-activity relationship (SAR) analysis for BBR analogues was done. Fourteen BBR analogues were designed, synthesized and biologically evaluated. SAR analysis revealed that appropriate modifications on the phenyl ring A or D of BBR might retain the up-regulatory activities on the expression of both LDLR and InsR. Among these compounds, compound 13a bearing 9-methoxy and 10-hydroxyl on the ring D showed promising activities on either LDLR or InsR gene expression. The 10-hydroxyl of 13a could be an arm to connect proper chemical groups for optimizing drug-bioavailability in vivo. Thus, 13a could be considered to be a parent compound to make pro-drugs for either blood lipids or glucose.
Reduction of conjugated nitroalkenes with zinc borohydride. A mild method for converting monosubstituted nitroalkenes to nitroalkanes and disubstituted ones to oximes
Ranu,Chakraborty
, p. 5317 - 5322 (2007/10/02)
Mono-β-substituted conjugated nitroalkenes are readily reduced by zinc borohydride in 1,2-dimethoxyethane to the corresponding nitroalkanes, whereas the disubstituted ones furnish the corresponding oximes in excellent yields.