128490-08-4Relevant articles and documents
Asymmetric Synthesis of Lysine Analogues with Reduced Basicity, and their Incorporation into Proteasome Inhibitors
de Bruin, Gerjan,van Rooden, Eva J.,Ward, David,Wesseling, Charlotte,van den Nieuwendijk, Adrianus M. C. H.,van Boeckel, Constant A. A.,Driessen, Christoph,Kisselev, Alexei F.,Florea, Bogdan I.,van der Stelt, Mario,Overkleeft, Herman S.
, p. 5921 - 5934 (2017/10/31)
Most known β2-selective proteasome inhibitors suffer from relatively poor cell permeability as the result of a net positive charge caused by the basic moiety at P1. In this paper, we describe the synthesis of oligopeptide vinyl sulfones that contain different amino acids bearing amino groups with reduced basicity at P1 and/or P3. For this, we developed the first enantioselective synthesis of lysine(4-ene) and lysine(4-yne). These amino acids, as well as histidine and diaminopropionic-acid-glycine, were incorporated at the P1 and/or P3 positions of oligopeptide vinyl sulfones. All inhibitors were found to inhibit β2, but with a loss of potency compared to our most potent and selective β2 inhibitor, LU-102. These results notwithstanding, our results provide important insights for the future design of β2-selective proteasome inhibitors.
The discovery and development of selective 3-fluoro-4-aryloxyallylamine inhibitors of the amine oxidase activity of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1)
Foot, Jonathan S.,Deodhar, Mandar,Turner, Craig I.,Yin, Ping,Van Dam, Ellen M.,Silva, Diego G.,Olivieri, Aldo,Holt, Andrew,McDonald, Ian A.
scheme or table, p. 3935 - 3940 (2012/07/03)
A new class of 3-fluoroallyl amine-based SSAO/VAP-1 inhibitors is reported. These compounds have excellent selectivity over diamine oxidase, MAO-A and MAO-B. Synthesis and SAR studies leading to compound 28 (PXS-4159A) are reported. The pharmacokinetic profile of 28 in the rat, together with activity in a murine model of lung inflammation are also disclosed.
Iridium-catalyzed asymmetric allylic amination with polar amines: Access to building blocks with lead-like molecular properties
Tosatti, Paolo,Horn, Joachim,Campbell, Amanda J.,House, David,Nelson, Adam,Marsden, Stephen P.
supporting information; experimental part, p. 3153 - 3157 (2011/03/18)
The combination of an air-stable iridium catalyst and the dipolar aprotic solvent dimethyl sulfoxide (DMSO) allowed, for the first time, the systematic exploitation of highly polar, functionalized amines in asymmetric allylic substitutions: low molecular
Combinatorial synthesis of libraries of macrocyclic compounds useful in drug discovery
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Page/Page column 11, (2010/02/11)
A library of macrocyclic compounds of the formula (I) where part (A) is a (CH2)y—NH— bivalent radical, a —(CH2)y— bivalent radical or a covalent bond; where part (B) is a (CH2)z—NH— bivalent radical, a —(CH2)z— bivalent radical, or a covalent bond; where part (C) is a (CH2)t—NH— bivalent radical, a —(CH2)t— bivalent radical, or a covalent bond; and where part (T) is a —Y-L-Z— radical wherein Y is CH2 or CO, Z is NH or O and L is a bivalent radical. These compounds are useful for carrying out screening assays or as intermediates for the synthesis of other compounds of pharmaceutical interest. A process for their preparation of these compounds in a combinatorial manner, is also disclosed.
A SELECTIVE 1,2-REDUCTION OF γ-AMINO-α,β-UNSATURATED ESTERS BY MEANS OF BF3.OEt2-DIBAL-H SYSTEM. HIGHLY VERSATILE CHIRAL BUILDING BLOCKS FROM α-AMINO ACIDS
Moriwake, Toshio,Hamano, Shin-ichi,Miki, Daiya,Saito, Seiki,Torii, Sigeru
, p. 815 - 818 (2007/10/02)
A combination of DIBAL-H with BF3.Et2O has been demonstrated to be a promising agent for a selective 1,2-reduction of γ-amino-α,β-unsaturated esters, which, otherwise, is difficult to realize and provides the route to potent chiral building blocks from α-
