Oligo-aspartic acid conjugates with benzo[c][2,6]naphthyridine-8-carboxylic acid scaffold as picomolar inhibitors of CK2
作者:Jürgen Vahter、Kaido Viht、Asko Uri、Erki Enkvist
DOI:10.1016/j.bmc.2017.02.055
日期:2017.4
class inhibitor taken to clinical trials. The most potentconjugates possessed two-digit picomolar affinity and clear selectivity for CK2α in a panel of 140 protein kinases. Labeling of the inhibitors with a fluorescent dye yielded probes for a fluorescence anisotropy-based binding/displacement assay which can be used for analysis of CK2 and precise determination of affinity of the highly potent (tight-binding)
Transforming Olefins into
<i>γ</i>
,
<i>δ</i>
‐Unsaturated Nitriles through Copper Catalysis
作者:Xuesong Wu、Jan Riedel、Vy M. Dong
DOI:10.1002/anie.201705859
日期:2017.9.11
We have developed a strategy to transform olefins into homoallylic nitriles through a mechanism that combines copper catalysis with alkyl nitrile radicals. The radicals are easily generated from alkyl nitriles in the presence of the mild oxidant di‐tert‐butyl peroxide. This cross‐dehydrogenative coupling between simple olefins and alkylnitriles bears advantages over the conventional use of halides
Betulinic Acid Derivatives: A New Class of Specific Inhibitors of Human Immunodeficiency Virus Type 1 Entry
作者:Françoise Soler、Christèle Poujade、Michel Evers、Jean-Christophe Carry、Yvette Hénin、Anne Bousseau、Thierry Huet、Rudi Pauwels、Erik De Clercq、Jean-François Mayaux、Jean-Bernard Le Pecq、Norbert Dereu
DOI:10.1021/jm950669u
日期:1996.1.1
A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. ''Time of addition'' experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.