- Design, Synthesis, and SAR Studies of Heteroarylpyrimidines and Heteroaryltriazines as CB2R Ligands
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Herein we describe the design and synthesis of a new series of heteroarylpyrimidine/heteroaryltriazine derivatives on the basis of quinazoline-2,4(1H,3H)-diones as CB2R-selective ligands using a bioisosterism strategy. An acetamide group was explored to displace the enamine linker of the lead compound for the purpose of stereoisomerism elimination and hydrophilicity increase. As a result, some of the synthesized compounds showed high bioactivity and selectivity for CB2R in calcium mobilization assays, and four displayed CB2R agonist activity, with EC50 values below 30 nm. The compound exhibiting the highest agonist activity toward CB2R (EC50=7.53±3.15 nm) had a selectivity over CB1R of more than 1328-fold. Moreover, structure–activity relationship (SAR) studies indicated that the substituents on the nucleus play key roles in the functionality of a ligand, with one such example demonstrating CB2R antagonist activity. Additionally, molecular docking simulations were conducted with the aim of better understanding of these new derivatives in relation to the structural requirements for agonists/antagonists binding to CB2R.
- Qian, Hai-Yan,Wang, Zhi-Long,Chen, Li-Li,Pan, You-Lu,Xie, Xiao-Yu,Xie, Xin,Chen, Jian-Zhong
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p. 2455 - 2463
(2018/11/23)
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- Photooxygenation of an amino-thienopyridone yields a more potent PTP4A3 inhibitor
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The phosphatase PTP4A3 is an attractive anticancer target, but knowledge of its exact role in cells remains incomplete. A potent, structurally novel inhibitor of the PTP4A family was obtained by photooxygenation of a less active, electron-rich thienopyrid
- Salamoun, Joseph M.,McQueeney, Kelley E.,Patil, Kalyani,Geib, Steven J.,Sharlow, Elizabeth R.,Lazo, John S.,Wipf, Peter
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supporting information
p. 6398 - 6402
(2016/07/16)
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- Heteroarylpyrimindinedione derivative and use thereof
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The invention provides a heteroarylpyrimindinedione derivative and use thereof. The heteroarylpyrimindinedione derivative comprises a compound with a structure shown as general formula I, and a pharmaceutically acceptable salt or hydrate thereof. The derivative is obtained by chemical synthesis, and pharmacological experiments prove that the active ligand with cannabinoid type II receptor CB2 can be used for preparation of drugs for prevention and mitigation of CB2 receptor-mediated diseases, and the drug is cannabinoid CB2 receptor agonist's agonist, partial agonist, inverse agonist or antagonist. And the general structural formula I is shown as the specification.
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- 2,4-Diaminothienopyrimidines as orally active antimalarial agents
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A novel series of 2,4-diaminothienopyrimidines with potential as antimalarials was identified from whole-cell high-throughput screening of a SoftFocus ion channel library. Synthesis and structure-activity relationship studies identified compounds with potent antiplasmodial activity and low in vitro cytotoxicity. Several of these analogues exhibited in vivo activity in the Plasmodium berghei mouse model when administered orally. However, inhibition of the hERG potassium channel was identified as a liability for this series.
- González Cabrera, Diego,Le Manach, Claire,Douelle, Frederic,Younis, Yassir,Feng, Tzu-Shean,Paquet, Tanya,Nchinda, Aloysius T.,Street, Leslie J.,Taylor, Dale,De Kock, Carmen,Wiesner, Lubbe,Duffy, Sandra,White, Karen L.,Zabiulla, K. Mohammed,Sambandan, Yuvaraj,Bashyam, Sridevi,Waterson, David,Witty, Michael J.,Charman, Susan A.,Avery, Vicky M.,Wittlin, Sergio,Chibale, Kelly
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p. 1014 - 1022
(2014/03/21)
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- THIENO [2,3-D] PYRIMIDINE COMPOUNDS AS INHIBITORS OF ADP-MEDIATED PLATELETS AGGREGATION
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I): wherein A1, A2, A3, A4, A5, A6, A7, A8, X4, X6, R2, R4, R5, and R6 are as defined in the detailed description of the invention. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
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Page/Page column 78
(2008/06/13)
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- Synthesis of Cyclic and Acyclic Nucleoside Analogues Having a Thiophene or Dihydrothiophene Ring Fused to the d Side of an Uracil
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Synthesis of cyclic and acyclic nucleosides was achieved by alkylation of various new aglycones following the Vorbrueggen and Niedballa's procedure .The analytical results allowed us to conclude that the alkylation ocurred on N1 site led to the β anomeric form for the cyclic nucleosides.
- Jourdan, Fabrice,Renault, Jacques,Karamat, Abdesselam,Ladurie, Daniel,Robba, Max
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p. 953 - 958
(2007/10/02)
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