100517-41-7Relevant articles and documents
Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection
Papageorgiou,Von Matt,Joergensen,Andersen,Wagner,Beerli,Than,Borer,Florineth,Rihs,Schreier,Weckbecker,Heusser
, p. 1986 - 1992 (2001)
The prevention of xenograft rejection is substantially dependent on inhibiting antibodies (Ab) produced by B-cells independently of T-cell signals (TI-1). Due to their ubiquitous biochemical mechanisms of action, the immunosuppressants currently employed
Naphthalimide and quinoline derivatives as inhibitors for insect N-acetyl-β-D-hexosaminidase
Yang, Huibin,Qi, Huitang,Liu, Tian,Shao, Xusheng,Yang, Qing,Qian, Xuhong
, p. 977 - 980 (2019)
Insect chitinolytic β-N-acetyl-D-hexosaminidase, such as OfHex1 from Ostrinia furnacalis, is a potential target for insecticide design. Among the known OfHex1 inhibitors, Q2 is of great interest because it is the first non-carbohydrate inhibitor. In this study, we designed and synthesized a series of Q2 derivatives by replacing the thiadiazole and naphthalimide groups and changing the linker length. Compound 3m showed the best inhibitory activity with a Ki value of 0.34 μmol/L against OfHex1, which is about one-quarter that of Q2 (Ki = 1.4 μmol/L). Compound 6a showed the best inhibitory activity among the quinoline-containing derivatives (Ki = 2.3 μmol/L). Molecular docking indicated that although 3m, 6a, and Q2 binding the active pocket of OfHex1 in similar mode, compound 3m engaged better than the other compounds in intermolecular interaction with OfHex1.
N-Ammonium Ylide Mediators for Electrochemical C-H Oxidation
Saito, Masato,Kawamata, Yu,Meanwell, Michael,Navratil, Rafael,Chiodi, Debora,Carlson, Ethan,Hu, Pengfei,Chen, Longrui,Udyavara, Sagar,Kingston, Cian,Tanwar, Mayank,Tyagi, Sameer,McKillican, Bruce P.,Gichinga, Moses G.,Schmidt, Michael A.,Eastgate, Martin D.,Lamberto, Massimiliano,He, Chi,Tang, Tianhua,Malapit, Christian A.,Sigman, Matthew S.,Minteer, Shelley D.,Neurock, Matthew,Baran, Phil S.
supporting information, p. 7859 - 7867 (2021/05/26)
The site-specific oxidation of strong C(sp3)-H bonds is of uncontested utility in organic synthesis. From simplifying access to metabolites and late-stage diversification of lead compounds to truncating retrosynthetic plans, there is a growing need for new reagents and methods for achieving such a transformation in both academic and industrial circles. One main drawback of current chemical reagents is the lack of diversity with regard to structure and reactivity that prevents a combinatorial approach for rapid screening to be employed. In that regard, directed evolution still holds the greatest promise for achieving complex C-H oxidations in a variety of complex settings. Herein we present a rationally designed platform that provides a step toward this challenge using N-ammonium ylides as electrochemically driven oxidants for site-specific, chemoselective C(sp3)-H oxidation. By taking a first-principles approach guided by computation, these new mediators were identified and rapidly expanded into a library using ubiquitous building blocks and trivial synthesis techniques. The ylide-based approach to C-H oxidation exhibits tunable selectivity that is often exclusive to this class of oxidants and can be applied to real-world problems in the agricultural and pharmaceutical sectors.
Synthesis, structure-activity relationships, cocrystallization and cellular characterization of novel smHDAC8 inhibitors for the treatment of schistosomiasis
Darwish, Salma,Erdmann, Frank,Ghazy, Ehab,Heimburg, Tino,Jung, Manfred,Lancelot, Julien,Pierce, Raymond,Robaa, Dina,Romier, Christophe,Schmidt, Matthias,Schmidtkunz, Karin,Shaik, Tajith B.,Simoben, Conrad V.,Sippl, Wolfgang,Truhn, Anne,Zeyen, Patrik
, (2021/08/17)
Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, we chemically optimized our previously reported benzhydroxamate-based inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the inhibition mode of smHDAC8 activity by the highly potent inhibitor 5o. Structure-based optimization of the novel inhibitors was carried out using the available crystal structures as well as docking studies on smHDAC8. The compounds were evaluated in screens for inhibitory activity against schistosome and human HDACs (hHDAC). The in vitro and docking results were used for detailed structure activity relationships. The synthesized compounds were further investigated for their lethality against the schistosome larval stage using a fluorescence-based assay. The most promising inhibitor 5o showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.
Pyrazole compound, salt and uses thereof,
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Paragraph 0244-0246; 0248, (2020/04/02)
The invention discloses a pyrazole compound and a salt thereof, wherein the structural formula of the pyrazole compound is represented by a formula (I). According to the invention, the pyrazole compound has good prevention and control effect on various gr
Heterocyclic compound and preparation and application thereof
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Paragraph 0210-0212, (2020/07/24)
The invention relates to bromodomain inhibitors, and provides a compound represented by a general formula I, a pharmaceutically acceptable salt, an enantiomer, a diastereoisomer, an atropisomer, a racemate, a polymorph, a solvate or an isotope-labeled compound (including deuterium substitution) thereof, a preparation method thereof, a pharmaceutical composition containing the same, and applicationthereof in pharmacy.
Pyrazole derivatives as well as preparation method and application thereof
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Paragraph 0269; 0271; 0272, (2020/01/08)
The invention discloses a derivative containing a pyrazole ring and quinoline structure, which has a very good control effect on various gramineous weeds and broadleaf weeds in agriculture or other fields, and can achieve a relatively good control effect even at a relatively low concentration. The herbicide controlling spectrum is expanded, weeds in crops can be killed by only one herbicide, and the herbicide is safe and reliable; the pyrazole derivative disclosed by the invention is relatively low in toxicity, few in residues in crops and small in harm to human and livestock, well solves theproblems of relatively high toxicity and more residues in crops of an existing herbicide, and improves the safety of agricultural production; the invention further provides a preparation method of thepyrazole derivative; in addition, the preparation method is few in step, easy in process operation, suitable for large-scale industrial production and good in application prospect.
WNT INHIBITORS FOR HUMAN STEM CELL DIFFERENTIATION
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Paragraph 0182, (2013/07/19)
Methods and small molecule compounds for stem cell differentiation and treatment of animals with diseases are provided. One example of a class of compounds that may be used is represented by the compound of Formula I and II: or a pharmaceutically acceptab
Wnt inhibition correlates with human embryonic stem cell cardiomyogenesis: A structure-activity relationship study based on inhibitors for the Wnt response
Lanier, Marion,Schade, Dennis,Willems, Erik,Tsuda, Masanao,Spiering, Sean,Kalisiak, Jaroslaw,Mercola, Mark,Cashman, John R.
experimental part, p. 697 - 708 (2012/04/10)
Human embryonic stem cell-based high-content screening of 550 known signal transduction modulators showed that one "lead" (1, a recently described inhibitor of the proteolytic degradation of Axin) stimulated cardiomyogenesis. Because Axin controls canonical Wnt signaling, we conducted an investigation to determine whether the cardiogenic activity of 1 is Wnt-dependent, and we developed a structure-activity relationship to optimize the cardiogenic properties of 1. We prepared analogues with a range of potencies (low nanomolar to inactive) for Wnt/β-catenin inhibition and for cardiogenic induction. Both functional activities correlated positively (r 2 = 0.72). The optimal compounds induced cardiogenesis 1.5-fold greater than 1 at 30-fold lower concentrations. In contrast, no correlation was observed for cardiogenesis and modulation of transforming growth factor β (TGFβ)/Smad signaling that prominently influences cardiogenesis. Taken together, these data show that Wnt signaling inhibition is essential for cardiogenic activity and that the pathway can be targeted for the design of druglike cardiogenic molecules.
Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists
Nelson, Derek W.,Gregg, Robert J.,Kort, Michael E.,Perez-Medrano, Arturo,Voight, Eric A.,Wang, Ying,Grayson, George,Namovic, Marian T.,Donnelly-Roberts, Diana L.,Niforatos, Wende,Honore, Prisca,Jarvis, Michael F.,Faltynek, Connie R.,Carroll, William A.
, p. 3659 - 3666 (2007/10/03)
1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X? receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution
