13675-94-0Relevant articles and documents
Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors
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
, p. 671 - 682 (2019)
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.
A Selective and Orally Bioavailable Quinoline-6-Carbonitrile-Based Inhibitor of CDK8/19 Mediator Kinase with Tumor-Enriched Pharmacokinetics
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
, p. 3420 - 3433 (2022/02/16)
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
AKT3 MODULATORS
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, (2021/11/13)
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.
Visible-Light-Photocatalyzed Reductions of N-Heterocyclic Nitroaryls to Anilines Utilizing Ascorbic Acid Reductant
Todorov, Aleksandar R.,Aikonen, Santeri,Muuronen, Mikko,Helaja, Juho
, p. 3764 - 3768 (2019/05/24)
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.
