30100-16-4Relevant articles and documents
Mechanically induced gelation of a kinetically trapped supramolecular polymer
Teunissen, Abraham J. P.,Nieuwenhuizen, Marko M. L.,Rodrguez-Llansola, Fransico,Palmans, Anja R. A.,Meijer
, p. 8429 - 8436 (2014)
The stimuli-induced gelation of a urethane-functionalized ditopic ureidopyrimidinone (UPy) compound is presented, and the mechanism by which the gelation proceeds is proposed. In a 40-120 mM solution in chloroform, the compound can exist in two different aggregated states, namely a low viscous mixture of (cyclic) oligomers or a fibrous gel. As evidenced by IR, NMR, and WAXS, the liquid state is stabilized by hydrogen bonds between the UPy and the back-folded chain, while the fibrous gel is stabilized by lateral hydrogen bonds within stacked UPy dimers. Controlled preparation techniques allow for pathway selection to arrive at one of both states. The remarkable long-term stability of the low viscous state (over 2 months for a 80 mM solution) is in contrast to the fast transformation into a gel by stirring in a few hours. Other mechanical stimuli like shaking, sonicating, and stirring for a shorter period, as well as freezing and thawing the solution, yield weaker gels than those obtained by long stirring. Heating the gels and slow cooling reversibly yield the nonviscous solution. This shows that the formation of UPy-urethane hydrogen bonds kinetically traps the UPy polymers, thereby preventing their lateral aggregation. The application of mechanical stress or freezing disrupts this interaction, allowing for the formation of a stacked nucleus on which further material can grow, eventually leading to gelation of the solution.
Self-aggregation inhibits the photonuclease activity of porphyrins.
Aoki, Katsumasa,Ishikawa, Yoshinobu,Oyama, Miyuki,Tomisugi, Yoshikazu,Uno, Tadayuki
, p. 899 - 903 (2003)
A series of tentacle porphyrins having four aminoalkyl groups at the periphery was synthesized, and the DNA binding properties were investigated by absorption and circular dichroism (CD) spectroscopic methods. The aminopropyl chain was found to facilitate binding, and bisignate induced CD spectra revealed that the porphyrins are self-stacked on the DNA surface. The photonuclease activity of the tentacle porphyrins was also studied, and the aminopropylporphyrin showed the highest activity. The activity increased in proportion to the porphyrin load, but higher loads resulted in the decrease of activity. This inhibitory step corresponded to aggregation of the porphyrin. Thus, the aggregation was suggested to shield the inner porphyrin from the solvent, the production of active oxygen species being suppressed.
A practical synthesis of ω-aminoalkanoic acid derivatives from cycloalkanones
Ho, Koc-Kan,O'Toole, Doris C.,Achan, Douglas M.,Lim, Kitae T.,Press, Jeffery B.,Leone-Bay, Andrea
, p. 2641 - 2649 (1996)
A practical synthetic route to N-Boc protected or Boc-amino acid coupled ω-aminoalkanoic acids is reported and exemplified by the preparation of 8-(t-butoxycarbonylamino)caprylic acid 2 and (N-t-butoxycarbonylphenylalanyl)-8-aminocaprylic acid 3. The sequence does not involve column chromatography, hydrogenation, azide or bromide related rearrangements, and therefore is amenable to scale-up. Homologues of the ω-aminoalkanoic acid derivatives may also be prepared by using different cycloalkanones.
Molecular Umbrellas Modulate the Selective Toxicity of Polyene Macrolide Antifungals
Skwarecki, Andrzej S.,Skarbek, Kornelia,Martynow, Dorota,Serocki, Marcin,Bylińska, Irena,Milewska, Maria J.,Milewski, S?awomir
, p. 1454 - 1465 (2018)
Antifungal polyene macrolide antibiotics Amphotericin B (AmB) and Nystatin (NYS) were conjugated through the ω-amino acid linkers with diwalled "molecular umbrellas" composed of spermidine-linked deoxycholic or cholic acids. The presence of "umbrella" substituents modulated biological properties of the antibiotics, especially their selective toxicity. Some of the AmB-umbrella conjugates demonstrated antifungal in vitro activity comparable to that of the mother antibiotic but diminished mammalian toxicity, especially the hemolytic activity. In contrast, antifungal in vitro activity of NYS-umbrella conjugates was strongly reduced and all these conjugates demonstrated poorer than NYS selective toxicity. No correlation between the aggregation state and hemolytic activity of the novel conjugates was found.
Design, synthesis and activity study of a novel PI3K degradation by hijacking VHL E3 ubiquitin ligase
Li, Chuchu,Liu, Xiaoqing,Ma, Mingliang,Wang, Haili
, (2022/03/31)
PI3K kinase plays an important role in regulating key processes in cells, such as cell growth, metabolism, proliferation, and apoptosis. The overexpression of PI3K kinase exists in many cancers. The proteolytic target chimera (PROTAC) technology is a new technology that uses the ubiquitin–proteasome system to degrade a given target protein. It has been described that CRBN-based PROTAC targets the degradation of PI3K kinase. However, PROTAC based on VHL has not been reported yet. Here, we connected the previously obtained highly active PI3K inhibitor to the VHL ligand through different small molecules, and obtained a series of PROTAC molecules targeting PI3K kinase. Obtain the most active compound through screening. It provides evidence for the feasibility of PROTAC technology to recruit VHL E3 ligase in PI3K kinase.
TARGET PROTEIN EED DEGRADATION-INDUCING DEGRADUCER, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DISEASES RELATED TO EED, EZH2, OR PRC2, COMPRISING SAME AS ACTIVE INGREDIENT
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, (2021/12/23)
The present invention relates to a target protein degradation-inducing Degraducer, a preparation method thereof, and a pharmaceutical composition for preventing or treating diseases related to EED, EZH2, or PRC2 comprising same as an active ingredient. A novel compound represented by formula 1, according to the present invention is a Degraducer compound that induces degradation of a target protein, i.e., embryonic ectoderm development (EED) or polycomb repressive complex 2 (PRC2), utilizing cereblon E3 ubiquitin ligase, von Hippel-Lindau tumor suppressor (VHL) E3 ubiquitin ligase, mouse double minute 2 homolog (MDM2) E3 ubiquitin ligase, and cellular inhibitor of apoptosis protein 1 (cIAP) E3 ubiquitin ligase, wherein the compound has an aspect of remarkably achieving target protein degradation-inducing activity through a ubiquitin proteasome system (UPS), and therefore there is a useful effect in that it is possible to provide a pharmaceutical composition for preventing or treating diseases or conditions related to a target protein, and a functional health food composition for preventing or improving same, comprising said compound as an active ingredient.
MACROCYCLIC COMPOUNDS USEFUL AS CHITINASE INHIBITORS
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Paragraph 0131; 0134-0135, (2021/07/29)
The present invention relates to macrocyclic compounds of formula (I) and their use as chitinase inhibitors as well as to pharmaceutical compositions and methods of preparation thereof. The compounds can in particular be used in the treatment, prevention and/or amelioration of asthma.
ERK5 DEGRADERS AS THERAPEUTICS IN CANCER AND INFLAMMATORY DISEASES
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Paragraph 00169; 00170, (2021/04/02)
Disclosed are bispecific compounds (degraders) that target ERK5 for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat cancer and inflammatory diseases.
GLYCOPEPTIDE COMPOUNDS, METHODS FOR PRODUCING THE SAME, AND USES THEREOF
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Paragraph 0158; 0160, (2020/12/14)
Disclosed herein are novel compounds and uses thereof. The present compounds are useful in suppressing the growth of various bacteria, including gram-positive and gram-negative bacteria. Accordingly, these compounds may be used to manufacture a medicament or pharmaceutic composition for treating disease and/or disorders associated with bacterial infection, especially antibiotic-resistant bacterial infection. Al so disclosed herein are methods for treating infectious diseases by use of the present compounds, medicament or pharmaceutical composition.
Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity
Ni, Jingxuan,Guo, Mengqi,Cao, Yucheng,Lei, Lei,Liu, Kangli,Wang, Binghua,Lu, Fangfang,Zhai, Rong,Gao, Xiangwei,Yan, Chunhong,Wang, Hongbo,Bi, Yi
, p. 122 - 131 (2018/11/23)
A series of novel fusidic acid (FA) derivatives were synthesized and screened for their in vitro cytotoxicity against the Hela, U87, KBV and MKN45 cancer cell lines. Selected FA derivatives with anti-tumor activity were firstly identified including compound 4, which exhibited good anti-proliferative activity with IC50 values in the range of 1.26–3.57 μM. Further research revealed that compound 4 induced Hela cells to undergo apoptosis by increasing the ratio of the cells in the Sub-G0/G1 phase via decreasing the neo-synthesized proteins in a dose-dependent manner from 1 to 10 μM. Compound 4 also showed good in vivo anti-tumor activity against the xenograft tumor of Hela cells and had no apparent toxicity. This study highlights the advantage of introducing the medium-length amino-terminal groups at the 3-OH position of FA to enhance its anti-tumor activity and suggests that compound 4 provides a starting point for designing more potent derivatives in the future.
