- De novo design, synthesis and evaluation of benzylpiperazine derivatives as highly selective binders of Mcl-1
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Considerable efforts have been made to the development of small-molecule inhibitors of antiapoptotic B-cell lymphoma 2 (Bcl-2) family proteins (such as Bcl-2, Bcl-xL, and Mcl-1) as a new class of anticancer therapies. Unlike general inhibitors
- Ding, Xiao,Li, Yan,Lv, Li,Zhou, Mi,Han, Li,Zhang, Zhengxi,Ba, Qian,Li, Jingquan,Wang, Hui,Liu, Hong,Wang, Renxiao
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p. 1986 - 2014
(2014/01/06)
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- Synthesis and structure-activity relationships of 4-hydroxy-4-phenylpiperidines as nociceptin receptor ligands: Part 2
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A series of 4-[2-(aminomethyl)phenyl]-1-[bis(2-chlorophenyl)methyl]-4-hydroxypiperidine analogs has been identified as nociceptin receptor ligands. These compounds display high affinity and functional activity at the nociceptin receptor. The synthesis and
- Ho, Ginny D.,Bercovici, Ana,Tulshian, Deen,Greenlee, William J.,Fawzi, Ahmad,Fernandez, Xiomara,McLeod, Robbie L.,Smith Torhan, April,Zhang, Hongtao
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p. 3028 - 3033
(2008/02/02)
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- N-sulfonylcarboximidamide apoptosis promoters
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Compounds having the formula are apoptosis promoters. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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Page/Page column 21
(2008/06/13)
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- Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors
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Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.
- Bolognesi, Maria Laura,Cavalli, Andrea,Andrisano, Vincenza,Bartolini, Manuela,Banzi, Rita,Antonello, Alessandra,Rosini, Michela,Melchiorre, Carlo
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p. 917 - 928
(2007/10/03)
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