- BIOCATALYST FOR CATALYTIC HYDROAMINATION
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The present invention relates to a method for the enzymatic hydroamination of C—C double bonds catalyzed by enzymes structurally and/or functionally related to phenylalanine ammonia lyase (PAL) isolated from microorganisms of Petroselinum crispum, Rhodoturula glutinis and/or functional active derivatives thereof.
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Page/Page column 11
(2012/05/21)
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- Design, synthesis, biological activity, and ADME properties of pyrazolo[3,4- d ]pyrimidines active in hypoxic human leukemia Cells: A lead optimization study
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A family of dual Src/Abl inhibitors characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold was previously reported by us and proved to be active against several tumor cell lines. Among these compounds, a promising antileukemia lead (1) has been recently identified, but, unfortunately, it suffers from substandard pharmaceutical properties. Accordingly, an approach for the optimization of the lead 1 is described in the present work. A series of more soluble pyrazolo[3,4-d]pyrimidine derivatives were rationally designed and proved to maintain the dual Src/Abl activity of the lead. Selected compounds showed an interesting activity profile against three different leukemic cells also in hypoxic conditions, which are usually characterized by imatinib-resistance. Finally, in vitro ADME properties (PAMPA permeation, water solubility, microsomal stability) for the most promising inhibitors were also evaluated, thus allowing the identification of a few optimized analogues of lead 1 as promising antileukemia agents.
- Radi, Marco,Dreassi, Elena,Brullo, Chiara,Crespan, Emmanuele,Tintori, Cristina,Bernardo, Vincenzo,Valoti, Massimo,Zamperini, Claudio,Daigl, Henry,Musumeci, Francesca,Carraro, Fabio,Naldini, Antonella,Filippi, Irene,Maga, Giovanni,Schenone, Silvia,Botta, Maurizio
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supporting information; experimental part
p. 2610 - 2626
(2011/06/21)
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- Azo Anions in Synthesis: α-Amino Carbanion Equivalents from t-Butyldiphenylmethylhydrazones
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α-Amino carbanion equivalents (=C(1-)NH2) and α-hydrazino anion equivalents (=C(1-)NHNH2) are readily accessible from the C-alkylation products of t-butyldiphenylmethylhydrazones; these azoalkanes can be efficiently transformed into amines, hydrazines, and also alkanes under mild reaction conditions.
- Baldwin, Jack E.,Adlington, Robert M.,Newington, Ian M.
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p. 176 - 178
(2007/10/02)
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