160232-23-5Relevant academic research and scientific papers
Probing pockets S2-S4′ of the γ-secretase active site with (hydroxyethyl)urea peptidomimetics
Esler, William P.,Das, Chittaranjan,Wolfe, Michael S.
, p. 1935 - 1938 (2004)
(Hydroxyethyl)urea peptidomimetics are potent inhibitors of γ-secretase that are accessible in a few synthetic steps. Systematic alteration of P2-P4′ revealed that the corresponding S2-S4′ active site pockets accommodate a variety of substituents, consistent with the fact that this protease cleaves a variety of single-pass membrane proteins; however, phenylalanine is not well tolerated at P2′. A compound spanning P2-P3′ was identified as a low nM inhibitor of γ-secretase activity both in cells and under cell-free conditions.
Design and biological evaluation of cinnamic and phenylpropionic amide derivatives as novel dual inhibitors of HIV-1 protease and reverse transcriptase
Zhu, Mei,Shan, Qi,Ma, Ling,Wen, Jiajia,Dong, Biao,Zhang, Guoning,Wang, Minghua,Wang, Juxian,Zhou, Jinming,Cen, Shan,Wang, Yucheng
, (2021/05/04)
Upon the basis of both possible ligand-binding site interactions and the uniformity of key residues in active sites, a novel class of HIV-1 PR/RT dual inhibitors was designed and evaluated. Cinnamic acids or phenylpropionic acids with more flexible chain and smaller steric hindrance were introduced into the inhibitors, giving rise to significant improvement in HIV-1 RT inhibitory activity by one or two orders of magnitude, with comparable or even improved potency against PR at the same time, compared with coumarin anologues in our previous studies. Among these inhibitors, 38d displayed a 19-fold improvement in anti-PR activity with IC50 value of 0.081 nM compared to the control DRV. In addition, inhibitor 38c exhibited an excellent anti-RT IC50 value of 0.43 μM, only a 4.7-fold less potent activity than the control EFV. More significantly, the disparate ratio between HIV-1 PR and RT inhibition became more reasonable with ratio of 1: 10.4, just as 37b. Furthermore, the assays on HIV-1 late stage and early stage supported the rationality of designing dual inhibitors. The SAR data as well as molecular modeling studies provided new insight for further optimization of more potent HIV-1 PR/RT dual inhibitors.
Synthesis and in vivo antimalarial evaluation of novel hydroxyethylamine derivatives
Souza, Mariana Concei??o De,Gon?alves-Silva, Triciana,Moreth, Marcele,Gomes, Claudia R. B.,Kaiser, Carlos Roland,Henriques, Maria Das Gra?as Muller De Oliveira,Souza, Marcus V. N. De
experimental part, p. 266 - 272 (2012/08/08)
A series of hydroxyethylamines has been synthesized from the reaction of (2S,3S )Boc-phenylalanine epoxide with alkyl amines in good yields and evaluated for their in vivo antimalarial activity in mice. Compound 4g presented better activity then the reference artesunate in percentage of inhibition of parasitemia in treated P. berghei-infected mice and compare to the activity of artesunate in the survival of mice 14 days after infection. In addiction, no hemolytic activity was found, which supports that inhibition of parasitemia is due to antimalarial activity. The compound 4g inhibited the differentiation to schizonts suggesting that parasite metabolism is a possible target of 4g. These results indicate that this class of compound possesses promising perspectives for the development of new antimalarial drugs.
Potent memapsin 2 (β-secretase) inhibitors: Design, synthesis, protein-ligand X-ray structure, and in vivo evaluation
Ghosh, Arun K.,Kumaragurubaran, Nagaswamy,Hong, Lin,Kulkarni, Sarang,Xu, Xiaoming,Miller, Heather B.,Srinivasa Reddy, Dandepally,Weerasena, Vajira,Turner, Robert,Chang, Wanpin,Koelsch, Gerald,Tang, Jordan
, p. 1031 - 1036 (2008/09/20)
Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic β-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memap
HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE
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Page 105, (2010/02/07)
The present invention relates to novel hydroxyethylamine compounds of formula (I): (I) having Asp2 (-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated-amyloid levels or-amyloid deposits, particularly Alzheimer's disease.
TRICYCLIC INDOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF ALZHEIMER’S DISEASE
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Page 36, (2010/02/09)
The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β- amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.
