- HETEROCYCLIC MITOCHONDRIAL ACTIVITY INHIBITORS AND USES THEREOF
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Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (A/K), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.
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Page/Page column 111
(2019/05/22)
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- Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design
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Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of β-amyloid peptides (pGlu-Aβ) and thus may participate in the pathogenesis of Alzheimer’s disease (AD). We designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, Aβ3E?42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering effect was achieved by incorporating an additional binding region into our previously established pharmacophoric model, resulting in strong interactions with the carboxylate group of Glu327 in the QC binding site. Our study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD.
- Hoang, Van-Hai,Tran, Phuong-Thao,Cui, Minghua,Ngo, Van T. H.,Ann, Jihyae,Park, Jongmi,Lee, Jiyoun,Choi, Kwanghyun,Cho, Hanyang,Kim, Hee,Ha, Hee-Jin,Hong, Hyun-Seok,Choi, Sun,Kim, Young-Ho,Lee, Jeewoo
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supporting information
p. 2573 - 2590
(2017/04/03)
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- Maytansinoid derivatives with peptide linker and conjugates thereof
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The invention relates to novel cell-binding agent-cytotoxic agent conjugate having a peptide linkers and more specifically to conjugates of formula (I). The invention also provides novel cytotoxic agents of formula (II), linker compounds represented by fo
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Page/Page column 107; 108
(2016/04/20)
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- Preparation of azobenzenealkanethiols for self-assembled monolayers with photoswitchable properties
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A series of azobenzenealkanethiol compounds with the structure p-RC 6H4N=NC6H4(CH2) nSH (n = 3, 4) was synthesized using a divergent strategy with the two anilines H2NC6H4(CH2) nSAc as central compounds. This strategy provides fast access to a broad variety of the respective azobenzenethiols without (note!) an oxygen atom in the alkyl chain, thus permitting the self-assembly of these compounds onto gold in a predictable conformation, also taking advantage of the previously found odd-even effect in aromatic-aliphatic hybrid systems. Initial experiments indicate that all of these molecules indeed form dense monolayers, in which the orientation of the azobenzene unit is determined by the number of methylene groups in the aliphatic part of the molecules. CSIRO 2010.
- Krakert, Simone,Terfort, Andreas
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scheme or table
p. 303 - 314
(2011/06/23)
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- MACROLIDE COMPOUNDS AND METHODS OF MAKING AND USING THE SAME
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The present invention provides amide containing macrocyclic compounds useful as therapeutic agents. More particularly, these compounds are useful as anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents.
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Page/Page column 117
(2008/12/07)
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- Optimized N-phenyl-N′-(2-chloroethyl)ureas as potential antineoplastic agents: Synthesis and growth inhibition activity
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In our ongoing research program aimed at the optimization of microtubule-self-assembly disrupting agents, we have prepared three series of phenylurea analogues (CEU), derived from N-(3-ω-hydroxyalkyl or 4-ω-hydroxyalkyl or 3-ω-hydroxyalkynyl)-phenyl-N′-(2
- Moreau, Emmanuel,Fortin, Sebastien,Desjardins, Michel,Rousseau, Jean L.C.,Petitclerc, Eric,C.-Gaudreault, Rene
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p. 6703 - 6712
(2007/10/03)
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- Pyrimidines and uses thereof
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The invention relates to pyrimidines and uses thereof, including to inhibit lysophosphatidic acid acyltransferase β (LPAAT-β) activity and/or proliferation of cells such as tumor-cells.
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- Iodine(V) reagents in organic synthesis. Part 2. Access to complex molecular architectures via Dess-Martin periodinane-generated o-imidoquinones
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o-Imidoquinones, a rather rare class of compounds, are prepared from anilides by the action of Dess-Martin pedodinane (DMP) and water. Their chemistry has been extensively investigated and found to lead to p-quinones and polycyclic systems of diverse mole
- Nicolaou,Sugita,Baran,Zhong
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p. 2221 - 2232
(2007/10/03)
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- Certain aryl-ureido anti-cancer agents
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The present invention is concerned with novel anticancer agents having potent antineoplastic activity without systemic toxicity and mutagenicity. The novel anticancer agents of the present invention are derivatives of formula I: STR1 wherein: A is O or NH
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- Regioselectivity of Diels-Alder Reactions of a Surfactant 1,3-Diene with Surfactant Dienophiles
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The ability of aqueous surfactant aggregates to control the regiochemistry of Diels-Alder reactions was investigated with surfactant 1,3-diene 4--1,3-butadien-2-yl>thio>-phenyl>-N,N,N-trimethyl-1-butanaminium bromide (6), deriv
- Jaeger, David A.,Wang, Jinkang
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p. 6745 - 6755
(2007/10/02)
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