128217-61-8Relevant articles and documents
Towards a universal organocatalyst for the synthesis of enantioenriched phenylalanine derivatives by enantioselective decarboxylative protonation
Pigeaux, Morgane,Laporte, Romain,Harrowven, David C.,Baudoux, Jér?me,Rouden, Jacques
supporting information, p. 4599 - 4603 (2016/09/23)
Access to enantioenriched non-proteogenic phenylalanine derivatives is described using the enantioselective decarboxylative protonation reaction of amidohemimalonate esters catalysed by various cinchona-based compounds. This study compares the catalytic efficiency as well as the enantioselectivity induced by three types of common organocatalysts, namely thioureas, squaramides and bis-cinchona squaramides. One of the main outcome of this work is the observation of a significant influence of the N-protecting group of the hemimalonate on its interaction with the catalyst. This methodology carried out under mild conditions exhibits good substrate scope and functional group tolerance. A substoichiometric amount of catalyst can also be used in certain cases while affording good yields and selectivities.
Discovery of a series of nonpeptide small molecules that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins
Chen,Zhu,Liu,Lu,Xie,Ling
, p. 4001 - 4010 (2007/10/03)
Insulin-like growth factors (IGF-I and II) play an important role in metabolic and mitogenic activities through stimulation of the IGF-I receptor on the cell surface. Although the concentration of IGF in blood and cerebrospinal fluid is quite high (>100 nM) this large pool of IGF is biologically inactive because of its association with six distinct binding proteins which form high-affinity complexes with IGF. Thus, inhibitors of IGF-binding proteins (IGFBPs), especially IGFBP-3, could potentially alter the distribution between the "free" and "bound" forms of IGF and thereby elevate biologically active IGF-I to exert a beneficial effect on those patients with diseases that respond to the application of exogenous IGF-I. Whereas IGF-I peptide variants which bind to IGFBPs but not the IGF-I receptor have been shown to be potent IGF/IGFBP inhibitors small molecule nonpeptide IGF/IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen. Here we report the discovery of several isoquinoline analogues, exemplified by 1 and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations. More importantly, both compounds were shown to be able to release biologically active IGF-I from the IGF-I/IGFBP-3 complex. These results point to the feasibility of developing orally active therapeutics to treat IGF-responsive diseases by optimization of the lead molecules 1 and 2.
