Citation: Xue-Ping Chu, Qing-Fa Zhou, Shen Zhao, Fei-Fei Ge, Mian Fu, Jia-Peng Chen, Tao Lu. Synthesis and biological evaluation of 3-amino-2-pyrones as selective cyclooxygenase-1 (COX-1) inhibitors[J]. Chinese Chemical Letters, ;2013, 24(2): 120-122. shu

Synthesis and biological evaluation of 3-amino-2-pyrones as selective cyclooxygenase-1 (COX-1) inhibitors

1.
Department of Organic Chemistry, China Pharmaceutical University, Nanjing 210009, China

Corresponding author: Qing-Fa Zhou, Tao Lu,
Received Date: 2 December 2012
Available Online: 27 December 2012
Fund Project: Wethank the National Natural Science Foundation of China (No. 21102179) (No. 21102179)Fundamental Research Funds for the Central Universities (No. JKZ2011011) for the financial support. (No. JKZ2011011)

A group of 3-amino-2-pyrones were synthesized and their biological activities were evaluated for inhibiting cyclooxygenase (COX) activity. This study has led to the identification of COX-1-selective inhibitors. Among the tested compounds, the compound 5j exhibited the most potent COX-1 inhibitory activity (IC₅₀ = 19.32 mg/mL) and COX-1 selectivity index (SI = 41.98).
- 3-Amino-2-pyrone,
- Biological activity,
- COX-1-selective inhibitor,
- Synthesis
1. [1]
  [1] C.J. Hawkey, COX-2 inhibitors, Lancet 353 (1999) 307-314.
2. [2]
  [2] W.L. Xie, J.G. Chipman, D.L. Robertson, R.L. Erikson, D.L. Simmons, Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing, Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 2692-2696.
3. [3]
  [3] S.A. Frautschy, Thinking outside the box about COX-1 in Alzheimer's disease, Neurobiol. Dis. 38 (2010) 492-494.
4. [4]
  [4] J.L. Teeling, C. Cunningham, T.A. Newman, V.H. Perry, The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: implications for a role of COX-1, Brain Behav. Immun. 24 (2010) 409-419.
5. [5]
  [5] (a) F. Wuest, X. Tang, T. Kniess, J. Pietzsch, M. Suresh, Synthesis and cyclooxygenase inhibition of various (aryl-1,2,3-triazole-1-yl)-methanesulfonylphenyl derivatives, Bioorg. Med. Chem. 17 (2009) 1146-1151;
6. [6]
  (b) M. Scholz, H.K. Ulbrich, O. Soehnlein, et al., Diaryl-dithiolanes and-isothiazoles: COX-1/COX-2 and 5-LOX-inhibitory, ^·OH scavenging and anti-adhesive activities, Bioorg. Med. Chem. 17 (2009) 558-568;
7. [7]
  (c) F. Wuest, T. Kniess, R. Bergmann, J. Pietzsch, Synthesis and evaluation in vitro and in vivo of a ¹¹C-labeled cyclooxygenase-2 (COX-2) inhibitor, Bioorg. Med. Chem. 16 (2008) 7660-7662;
8. [8]
  (d) A.S. Kalgutkar, Selective cyclooxygenase-2 inhibitors as non-ulcerogenic antiinflammatory agents, Exp. Opin. Ther. Patents 8 (1999) 831-849;
9. [9]
  (e) T.D. Penning, J.J. Talley, S.R. Bertenshaw, et al., Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib), J. Med. Chem. 40 (1997) 1347-1365.
10. [10]
  [6] (a) H. Kakuta, R. Fukai, X. Zheng, et al., Identification of urine metabolites of TFAP, a cyclooxygenase-1 inhibitor, Bioorg. Med. Chem. Lett. 20 (2010) 1840-1843;
11. [11]
  (b) H. Sano, T. Noguchi, A. Miyajma, Y. Hashimoto, H. Miyachi, Anti-angiogenic activity of basic-type, selective cyclooxygenase (COX)-1 inhibitors, Bioorg. Med. Chem. Lett. 16 (2006) 3068-3072;
12. [12]
  (c) H. Sano, T. Noguchi, A. Tanatni, Y. Hashimoto, H. Miyachi, Design and synthesis of subtype-selective cyclooxygenase (COX) inhibitors derived from thalidomide, Bioorg. Med. Chem. 13 (2005) 3079-3091;
13. [13]
  (d) T. Noguchi, R. Shimazawa, K. Nagasawa, Y. Hashimoto, Thalidomide and its analogues as cyclooxygenase inhibitors, Bioorg. Med. Chem. Lett. 12 (2002) 1043-1046.
14. [14]
  [7] (a) M.C. Allison, A.G. Howatson, C.J. Torrance, F.D. Lee, R.I. Russell, Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs, N. Engl. J. Med. 327 (1992) 749-754;
15. [15]
  (b) J.R. Vane, Y.S. Bakhle, R.M. Botting, Cyclooxygenase 1 and 2, Annu. Rev. Pharmacol. Toxicol. 38 (1998) 97-120.
16. [16]
  [8] (a) J.M. Dickinson, Microbial pyran-2-ones and dihydropyran-2-ones, Nat. Prod. Rep. 10 (1993) 71-98;
17. [17]
  (b) G.P. McGlacken, I.J.S Fairlamb, 2-Pyrone natural products and mimetics: isolation, characterization and biological activity, Nat. Prod. Rep. 22 (2005) 369-385.
18. [18]
  [9] J.V.N. Vara Prasad, K.S. Para, E.A. Lunney, et al., Novel series of achiral, low molecular weight, and potent HIV-1 protease inhibitors, J. Am. Chem. Soc. 116 (1994) 6989-6990.
19. [19]
  [10] A. Kanai, T. Kamino, K. Kuramochi, S. Kobayashi, Synthetic studies directed toward the assembly of the C-glycoside fragment of the telomerase inhibitor D8646-2-6, Org. Lett. 5 (2003) 2837-2839.
20. [20]
  [11] (a) A.F. Barrero, J.E. Oltra, M.M. Herrador, et al., Gibepyrones: a-pyrones from Gibberella fujikuroi, Tetrahedron 49 (1993) 141-150;
21. [21]
  (b) W.R. Abraham, H. Arfmann, Fusalanipyrone, a monoterpenoid from Fusarium solani, Phytochemistry 27 (1988) 3310-3311.
22. [22]
  [12] (a) A. Evidente, A. Cabras, L. Maddau, et al., Viridepyronone, a new antifungal 6-substituted 2H-pyran-2-one produced by Trichoderma viride, J. Agric. Food Chem. 51 (2003) 6957-6960;
23. [23]
  (b) A. Simon, R.W. Dunlop, E.L. Ghisalberti, K. Sivasithamparam, Trichoderma koningii produces a pyrone compound with antibiotic properties, Soil Biol. Biochem. 20 (1988) 263-264;
24. [24]
  (c) N. Claydon, M. Asllan, J.R. Hanson, A.G. Avent, Antifungal alkyl pyrones of Trichoderma harzianum, Trans. Br. Mycol. Soc. 88 (1987) 503-513;
25. [25]
  (d) H.G. Cutler, R.H. Cox, F.G. Crumley, P.O. Cole, 6-Pentyl-a-pyrone from Trichoderma harzianum: its plant growth inhibitory and antimicrobial properties, Agric. Biol. Chem. 50 (1986) 2943-2945.
26. [26]
  [13] K.K. Chen, A.J. Kovarikova, Pharmacology and toxicology of toad venom, J. Pharm. Sci. 56 (1967) 1535-1541.
27. [27]
  [14] X. Shi, W.S. Leal, Z. Liu, E. Schrader, J. Meinwald, A new synthesis of alkylated 2Hpyran-2-ones and its application to the determination of the relative and absolute configuration of supellapyrone, sex pheromone of the brownbanded cockroach, Supella longipalpa, Tetrahedron Lett. 36 (1995) 71-74.
28. [28]
  [15] G. Schlingmann, L. Milne, G.T. Carter, New a-pyrones produced by fungal culture LL-11G219 function as androgen receptor ligands, Tetrahedron 54 (1998) 13013-13022.
29. [29]
  [16] H. Sato, K. Konoma, S. Sakamura, Three new phytotoxins produced by Pyrenochaeta terrestris: pyrenochaetic acids A, B and C, Agric. Biol. Chem. 45 (1981) 1675-1679.
30. [30]
  [17] S. Hagen, J.V.N. Vara Prasa, B.D. Tait, Nonpeptide inhibitors of HIV protease, Adv. Med. Chem. 5 (2000) 159-195.
31. [31]
  [18] (a) L.R. Marrison, J.M. Dickinson, I.J.S. Fairlamb, Bioactive 4-substituted-6-methyl-2-pyrones with promising cytotoxicity against A2780 and K562 cell lines, Bioorg. Med. Chem. Lett. 12 (2002) 3509-3513;
32. [32]
  (b) L.R. Marrison, J.M. Dickinson, I.J.S. Fairlamb, Suzuki cross-coupling approaches to the synthesis of bioactive 3-substituted and 5-substituted-4-methoxy-6-methyl-2-pyrones, Bioorg. Med. Chem. Lett. 13 (2003) 2667-2671.
33. [33]
  [19] (a) P.N. Praveen Rao, M. Amini, H. Li, A.G. Habeeb, E.E. Knaus, Design, synthesis, and biological evaluation of 6-substituted-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones: a novel class of diarylheterocyclic selective cyclooxygenase-2 inhibitors, J. Med. Chem. 46 (2003) 4872-4882;
34. [34]
  (b) P.N. Praveen Rao, M.J. Uddin, E.E. Knaus, Design, synthesis, and structure-activity relationship studies of 3,4,6-triphenylpyran-2-ones as selective cyclooxygenase-2 inhibitors, J. Med. Chem. 47 (2004) 3972-3990.
35. [35]
  [20] (a) Q.F. Zhou, Y. Zhu, W.F. Tang, T. Lu, Michael addition-lactonization reaction of electron-deficient alkynes with N-(diphenylmethylene)glycinates: an efficient synthesis of 3-amino-2-pyrone derivatives, Synthesis (2010) 211-216;
36. [36]
  (b) Q.F. Zhou, S. Zhao, X. Wang, T. Lu, Research progress in the synthesis of 2-pyrone derivatives, Chin. J. Org. Chem. 30 (2010) 1652-1663.
37. [37]
  [21] W. Duan, L. Zhang, Cyclooxygenase inhibitors not inhibit resting lung cancer A549 cell proliferation, Prostaglandins Leukot Essent Fatty Acids 74 (2006) 317-321.
1. [1]
  Yulong Shi , Fenbei Chen , Mengyuan Wu , Xin Zhang , Runze Meng , Kun Wang , Yan Wang , Yuheng Mei , Qionglu Duan , Yinghong Li , Rongmei Gao , Yuhuan Li , Hongbin Deng , Jiandong Jiang , Yanxiang Wang , Danqing Song . Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1. Chinese Chemical Letters, 2024, 35(5): 108792-. doi: 10.1016/j.cclet.2023.108792
2. [2]
  Tao Yu , Vadim A. Soloshonok , Zhekai Xiao , Hong Liu , Jiang Wang . Probing the dynamic thermodynamic resolution and biological activity of Cu(Ⅱ) and Pd(Ⅱ) complexes with Schiff base ligand derived from proline. Chinese Chemical Letters, 2024, 35(4): 108901-. doi: 10.1016/j.cclet.2023.108901
3. [3]
  Ping Sun , Yuanqin Huang , Shunhong Chen , Xining Ma , Zhaokai Yang , Jian Wu . Indole derivatives as agrochemicals: An overview. Chinese Chemical Letters, 2024, 35(7): 109005-. doi: 10.1016/j.cclet.2023.109005
4. [4]
  Wei Sun , Anjing Liao , Li Lei , Xu Tang , Ya Wang , Jian Wu . Research progress on piperidine-containing compounds as agrochemicals. Chinese Chemical Letters, 2025, 36(1): 109855-. doi: 10.1016/j.cclet.2024.109855
5. [5]
  Anqiu LIU , Long LIN , Dezhi ZHANG , Junyu LEI , Kefeng WANG , Wei ZHANG , Junpeng ZHUANG , Haijun HAO . Synthesis, structures, and catalytic activity of aluminum and zinc complexes chelated by 2-((2,6-dimethylphenyl)amino)ethanolate. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 791-798. doi: 10.11862/CJIC.20230424
6. [6]
  Bairu Meng , Zongji Zhuo , Han Yu , Sining Tao , Zixuan Chen , Erik De Clercq , Christophe Pannecouque , Dongwei Kang , Peng Zhan , Xinyong Liu . Design, synthesis, and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs. Chinese Chemical Letters, 2024, 35(6): 108827-. doi: 10.1016/j.cclet.2023.108827
7. [7]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
8. [8]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
9. [9]
  Jia Chen , Yun Liu , Zerong Long , Yan Li , Hongdeng Qiu . Colorimetric detection of α-glucosidase activity using Ni-CeO₂ nanorods and its application to potential natural inhibitor screening. Chinese Chemical Letters, 2024, 35(9): 109463-. doi: 10.1016/j.cclet.2023.109463
10. [10]
  Mianling Yang , Meehyein Kim , Peng Zhan . Modular miniaturized synthesis and in situ biological evaluation facilitate rapid discovery of potent MraY inhibitors as antibacterial agents. Chinese Chemical Letters, 2025, 36(2): 110455-. doi: 10.1016/j.cclet.2024.110455
11. [11]
  Guoping Yang , Zhoufu Lin , Xize Zhang , Jiawei Cao , Xuejiao Chen , Yufeng Liu , Xiaoling Lin , Ke Li . Assembly of Y(Ⅲ)-containing antimonotungstates induced by malic acid with catalytic activity for the synthesis of imidazoles. Chinese Chemical Letters, 2024, 35(12): 110274-. doi: 10.1016/j.cclet.2024.110274
12. [12]
  Yao HUANG , Yingshu WU , Zhichun BAO , Yue HUANG , Shangfeng TANG , Ruixue LIU , Yancheng LIU , Hong LIANG . Copper complexes of anthrahydrazone bearing pyridyl side chain: Synthesis, crystal structure, anticancer activity, and DNA binding. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 213-224. doi: 10.11862/CJIC.20240359
13. [13]
  Rong-Nan Yi , Wei-Min He . Photocatalytic Minisci-type multicomponent reaction for the synthesis of 1-(halo)alkyl-3-heteroaryl bicyclo[1.1.1]pentanes. Chinese Chemical Letters, 2024, 35(10): 110115-. doi: 10.1016/j.cclet.2024.110115
14. [14]
  Gangsheng Li , Xiang Yuan , Fu Liu , Zhihua Liu , Xujie Wang , Yuanyuan Liu , Yanmin Chen , Tingting Wang , Yanan Yang , Peicheng Zhang . Three-step synthesis of flavanostilbenes with a 2-cyclohepten-1-one core by Cu-mediated [5 + 2] cycloaddition/decarboxylation cascade. Chinese Chemical Letters, 2025, 36(2): 109880-. doi: 10.1016/j.cclet.2024.109880
15. [15]
  Jian Song , Shenghui Wang , Qiuge Liu , Xiao Wang , Shuo Yuan , Hongmin Liu , Saiyang Zhang . N-Benzyl arylamide derivatives as novel and potent tubulin polymerization inhibitors against gastric cancers: Design, structure–activity relationships and biological evaluations. Chinese Chemical Letters, 2025, 36(2): 109678-. doi: 10.1016/j.cclet.2024.109678
16. [16]
  Chong Liu , Ling Li , Jiahui Gao , Yanwei Li , Nazhen Zhang , Jing Zang , Cong Liu , Zhaopei Guo , Yanhui Li , Huayu Tian . The study of antibacterial activity of cationic poly(β-amino ester) regulating by amphiphilic balance. Chinese Chemical Letters, 2025, 36(2): 110118-. doi: 10.1016/j.cclet.2024.110118
17. [17]
  Maitri Bhattacharjee , Rekha Boruah Smriti , R. N. Dutta Purkayastha , Waldemar Maniukiewicz , Shubhamoy Chowdhury , Debasish Maiti , Tamanna Akhtar . Synthesis, structural characterization, bio-activity, and density functional theory calculation on Cu(Ⅱ) complexes with hydrazone-based Schiff base ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1409-1422. doi: 10.11862/CJIC.20240007
18. [18]
  Xiaomeng Hu , Jie Yu , Lijie Sun , Linfeng Zhang , Wei Zhou , Dongpeng Yan , Xinrui Wang . Synthesis of an AVB@ZnTi-LDH composite with synergistically enhance UV blocking activity and high stability for potential application in sunscreen formulations. Chinese Chemical Letters, 2024, 35(11): 109466-. doi: 10.1016/j.cclet.2023.109466
19. [19]
  Liyong Ding , Zhenhua Pan , Qian Wang . 2D photocatalysts for hydrogen peroxide synthesis. Chinese Chemical Letters, 2024, 35(12): 110125-. doi: 10.1016/j.cclet.2024.110125
20. [20]
  Junjun Huang , Ran Chen , Yajian Huang , Hang Zhang , Anran Zheng , Qing Xiao , Dan Wu , Ruxia Duan , Zhi Zhou , Fei He , Wei Yi . Discovery of an enantiopure N-[2-hydroxy-3-phenyl piperazine propyl]-aromatic carboxamide derivative as highly selective α_1D/1A-adrenoceptor antagonist and homology modelling. Chinese Chemical Letters, 2024, 35(11): 109594-. doi: 10.1016/j.cclet.2024.109594

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(1254)
HTML views(23)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142