- The discovery of quinoline derivatives, as NF-κB inducing kinase (NIK) inhibitors with anti-inflammatory effects in vitro, low toxicities against T cell growth
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NIK is a critical regulatory protein of the non-classical NF-kB pathway, and its dysregulated activation has been proved to be one of the pathogenic factors in a variety of autoimmune diseases and inflammatory diseases. Nevertheless, its corresponding dev
- Song, Jianing,Zhu, Yuqin,Zu, Weidong,Duan, Chunqi,Xu, Junyu,Jiang, Fei,Wang, Xinren,Li, Shuwen,Liu, Chenhe,Gao, Qianqian,Li, Hongmei,Zhang, Yanmin,Tang, Weifang,Lu, Tao,Chen, Yadong
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Read Online
- A Selective and Orally Bioavailable Quinoline-6-Carbonitrile-Based Inhibitor of CDK8/19 Mediator Kinase with Tumor-Enriched Pharmacokinetics
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Senexins are potent and selective quinazoline inhibitors of CDK8/19 Mediator kinases. To improve their potency and metabolic stability, quinoline-based derivatives were designed through a structure-guided strategy based on the simulated drug–target dockin
- Zhang, Li,Cheng, Chen,Li, Jing,Wang, Lili,Chumanevich, Alexander A.,Porter, Donald C.,Mindich, Aleksei,Gorbunova, Svetlana,Roninson, Igor B.,Chen, Mengqian,McInnes, Campbell
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p. 3420 - 3433
(2022/02/16)
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- AKT3 MODULATORS
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Compounds of Formula la, lb, or Ic, (Ia); (Ib); or (Ic), are described, where the various substituents are defined herein. The compounds can modulate a property or effect of Akt3 in vitro or in vivo, and can also be used, individually or in combination with other agents, in the prevention or treatment of a variety of conditions. Methods for synthesizing the compounds are described. Pharmaceutical compositions and methods of using these compounds or compositions, individually or in combination with other agents or compositions, in the prevention or treatment of a variety of conditions are also described.
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Paragraph 0368; 0369
(2021/11/13)
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- AKT3 MODULATORS
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Compounds of Formula la, lb, or Ic, are described, where the various substituents are defined herein. The compounds can modulate a property or effect of Akt3 in vitro or in vivo, and can also be used, individually or in combination with other agents, in the prevention or treatment of a variety of conditions. Methods for synthesizing the compounds are described. Pharmaceutical compositions and methods of using these compounds or compositions, individually or in combination with other agents or compositions, in the prevention or treatment of a variety of conditions are also described.
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Paragraph 0368
(2021/11/13)
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- QUINOLINE-BASED COMPOUNDS AND METHODS OF INHIBITING CDK8/19
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Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted qunioline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.
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Paragraph 0108; 0110-0111; 0116
(2020/03/09)
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- Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors
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In this study, amino-oxy-diarylquinolines were designed using structure-guided molecular hybridization strategy and fusing of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), etravirine (ETV, TMC125) and rilpivirine (RPV, TMC278). The anti-HIV-1 reverse transcriptase (RT) activity was evaluated using standard ELISA method, and the cytotoxic activity was performed using MTT and XTT assays. The primary bioassay results indicated that 2-amino-4-oxy-diarylquinolines possess moderate inhibitory properties against HIV-1 RT. Molecular docking results showed that 2-amino-4-oxy-diarylquinolines 8(a-d) interacted with the Lys101 and His235 residue though hydrogen bonding and interacted with Tyr318 residue though π-π stacking in HIV-1 RT. Furthermore, 8a and 8d were the most potent anti-HIV agents among the designed and synthesized compounds, and their inhibition rates were 34.0% and 39.7% at 1 μM concentration. Interestingly, 8a was highly cytotoxicity against MOLT-3 (acute lymphoblastic leukemia), with an IC 50 of 4.63±0.62 μg/mL, which was similar with that in EFV and TMC278 (IC 50 7.76±0.37 and 1.57±0.20 μg/ml, respectively). Therefore, these analogs of the synthesized compounds can serve as excellent bases for the development of new anti-HIV-1 agents in the near future.
- Makarasen, Arthit,Kuno, Mayuso,Patnin, Suwicha,Reukngam, Nanthawan,Khlaychan, Panita,Deeyohe, Sirinya,Intachote, Pakamas,Saimanee, Busakorn,Sengsai, Suchada,Boonsri, Pornthip,Chaivisuthangkura, Apinya,Sirithana, Wandee,Techasakul, Supanna
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p. 671 - 682
(2019/12/09)
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- Visible-Light-Photocatalyzed Reductions of N-Heterocyclic Nitroaryls to Anilines Utilizing Ascorbic Acid Reductant
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A photoreductive protocol utilizing [Ru(bpy)3]2+ photocatalyst, blue light LEDs, and ascorbic acid (AscH2) has been developed to reduce nitro N-heteroaryls to the corresponding anilines. Based on experimental and computational results and previous studies, we propose that the reaction proceeds via proton-coupled electron transfer between AscH2, photocatalyst, and the nitro N-heteroaryl. The method offers a green catalytic procedure to reduce, e.g., 4-/8-nitroquinolines to the corresponding aminoquinolines, substructures present in important antimalarial drugs.
- Todorov, Aleksandar R.,Aikonen, Santeri,Muuronen, Mikko,Helaja, Juho
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supporting information
p. 3764 - 3768
(2019/05/24)
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- 2, 6-Di-Nitrogen-Containing Substituted Purine Derivative, And Preparation Method, Pharmaceutical Composition And Use Thereof
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The present invention provides a 2, 6-di-nitrogen-containing substituted purine derivative having a formula (I) structure, or pharmaceutical salt or hydrate thereof, and preparation method and use thereof. The compound is broad spectrum anticancer, low to
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Paragraph 0109; 0111
(2016/08/17)
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- Application of fragment screening and merging to the discovery of inhibitors of the mycobacterium tuberculosis cytochrome P450 CYP121
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Pieces of the puzzle: The first fragment-based approach was used to target cytochrome P450 enzymes (CYPs) for drug development (see scheme). The experiments provide new insights into the binding site of the essential Mycobacterium tuberculosis CYP121 enzyme, and resulted in a promising novel lead compound based on fragment merging.
- Hudson, Sean A.,McLean, Kirsty J.,Surade, Sachin,Yang, Yong-Qing,Leys, David,Ciulli, Alessio,Munro, Andrew W.,Abell, Chris
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p. 9311 - 9316
(2012/10/30)
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- Synthesis and biological evaluation of 4-anilinoquinolines as potent inhibitors of epidermal growth factor receptor
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The mutant receptor tyrosine kinase EGFR is a validated and therapeutically amenable target for genotypically selected lung cancer patients. Here we present the synthesis and biological evaluation of a series of 6- and 7-substituted 4-anilinoquinolines as potent type I inhibitors of clinically relevant mutant variants of EGFR. Quinolines 3a and 3e were found to be highly active kinase inhibitors in biochemical assays and were further investigated for their biological effect on EGFR-dependent Ba/F3 cells and non-small cell lung cancer (NSCLC) cell lines.
- Pawar, Vijaykumar G.,Sos, Martin L.,Rode, Haridas B.,Rabiller, Matthias,Heynck, Stefanie,Van Otterlo, Willem A. L.,Thomas, Roman K.,Rauh, Daniel
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supporting information; experimental part
p. 2892 - 2901
(2010/08/05)
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