Chinese Journal of Organic Chemistry >
Synthesis and Biological Activities of Dihydrooxazolo[5,4-d]-pyrrolo[1,2-a]pyrimidinones
Received date: 2021-07-02
Revised date: 2021-09-06
Online published: 2022-02-24
Supported by
West Light Foundation of Chinese Academy of Sciences(2018-XBQNXZ-B-004)
Based on the general framework of natural alkaloid deoxyvasicinone, forty dihydrooxazolo[5,4-d]pyrrolo[1,2-a]- pyrimidinone compounds were designed and synthesized through bioisosterism strategy. The novel compounds were confirmed by 1H NMR, 13C NMR and HRMS spectra. The main factors affecting the reactions of synthesis and the structure-activity relationships (SARs) were investigated. The activities of the target compounds against three cancer cell lines (MCF-7, HeLa and A549) were evaluated by methyl thiazolyl tetrazolium (MTT) in vitro. All the compounds were also evaluated for their antimicrobial activities by agar punch method. The results showed that 2-(naphthalen-1-yl)-6,7-dihydrooxazolo[5,4-d]- pyrrolo[1,2-a]pyrimidin-9(5H)-one (E12) and 2-(4-(trifluoromethoxy)phenyl)-6,7-dihydrooxazolo[5,4-d]pyrrolo[1,2-a]pyrimidin-9(5H)-one (E39) exhibited relatively better anti-proliferative activities against HeLa and MCF-7 cancer cell lines, with the half maximal inhibitory concentration (IC50) values of (4.59±0.10), (6.89±1.26) μmol•L–1, respectively. 2-((3R,5R,7R)- Adamantan-1-yl)-6,7-dihydrooxazolo[5,4-d]pyrrolo[1,2-a]pyrimidin-9(5H)-one (E6) and 2-(3,5-dichlorophenyl)-6,7-dihydrooxazolo[5,4-d]pyrrolo[1,2-a]pyrimidin-9(5H)-one (E28) showed good antimicrobial activity to C. albicans, E. coli and S. aureus.
Yan Zeng , Lifei Nie , Chao Niu , Aytilla Mamatjan , Khurshed Bozorov , Jiangyu Zhao , Haji Akber Aisa . Synthesis and Biological Activities of Dihydrooxazolo[5,4-d]-pyrrolo[1,2-a]pyrimidinones[J]. Chinese Journal of Organic Chemistry, 2022 , 42(2) : 543 -556 . DOI: 10.6023/cjoc202107002
| [1] | Alshamma, A.; Drake, S.; Flynn, D. L.; Mitscher, L. A.; Park, Y. H.; Rao, G. S. R.; Simpson, A.; Swayze, J. K.; Veysoglu, T.; Wu, S. T. - S. J. Nat. Prod. 1981, 44, 745. |
| [2] | Mohr, N.; Budzikiewicz, H.; Korth, H.; Pulverer, und. G. Liebigs Ann. Chem. 1981, 1515. |
| [3] | Okmanov, R. Y.; Tashkhodzhaev, B.; Khakimova, Z. M.; Tulyaganov, T. S.; Shakhidoyatov, K. M. Chem. Nat. Compd. 2010, 46, 59. |
| [4] | Wu, X.-Y.; Qin, G.-W.; Cheung, K. K.; Cheng, K. F. Tetrahedron 1997, 53, 13323. |
| [5] | Molina, P.; Tárraga, A.; Gonzalez-Tejero, A.; Rioja, I.; Ubeda, A.; Terencio, M. C.; Alcaraz, M. J. J. Nat. Prod. 2001, 64, 1297. |
| [6] | Wang, C.-H.; Zeng, H.; Wang, Y.-H.; Li, C.; Cheng, J.; Ye, Z.-J.; He, X.-J. J. Asian Nat. Prod. Res. 2015, 17, 595. |
| [7] | Potewar, T. M.; Ingale, S. A.; Srinivasan, K. V. ARKIVOC 2008, 100. |
| [8] | Nepali, K.; Sharma, S.; Ojha, R.; Dhar, K. L. Med. Chem. Res. 2013, 22, 1. |
| [9] | Zhang, H.-Z.; Zhao, Z.-L.; Zhou, C.-H. Eur. J. Med. Chem. 2018, 144, 444. |
| [10] | Zhang, H.-Z.; Gan, L.-L.; Wang, H.; Zhou, C.-H. Mini-Rev. Med. Chem. 2017, 17, 122. |
| [11] | Zhang, L.; Peng, X.-M.; Damu, G. L. V.; Geng, R.-X.; Zhou, C.-H. Med. Res. Rev. 2014, 34, 340. |
| [12] | Zhou, C.-H.; Wang, Y. Curr. Med. Chem. 2012, 19, 239. |
| [13] | Seenaiah, D.; Reddy, P. R.; Reddy, G. M.; Padmaja, A.; Padmavathi, V.; Krishna, N. S. Eur. J. Med. Chem. 2014, 77, 1. |
| [14] | Tropcheva, R.; Lesev, N.; Danova, S.; Stoitsova, S.; Kaloyanova, S. J. Photochem. Photobiol.,B 2015, 143, 120. |
| [15] | Zhang, Y.; Bao, J.; Deng, X.-X.; He, W.; Fan, J.-J.; Jiang, F.-Q.; Fu, L. Bioorg. Med. Chem. Lett. 2016, 26, 4081. |
| [16] | Li, Z.; Gever, J. R.; Rao, S.; Widjaja, K.; Prusiner, S. B.; Silber, B. M. ACS Med. Chem. Lett. 2013, 4, 397. |
| [17] | Bernard, A. M.; Cabiddu, M. G.; De Montis, S.; Mura, R.; Pompei, R. Biorg. Med. Chem. 2014, 22, 4061. |
| [18] | Henderson, J. A.; Bilimoria, D.; Bubenik, M.; Cadilhac, C.; Cottrell, K. M.; Denis, F.; Dietrich, E.; Ewing, N.; Falardeau, G.; Giroux, S.; L'Heureux, L.; Liu, B.; Mani, N.; Morris, M.; Nicolas, O.; Pereira, O. Z.; Poisson, C.; Reddy, T. J.; Selliah, S.; Shawgo, R. S.; Vaillancourt, L.; Wang, J.; Xu, J.; Chauret, N.; Berlioz-Seux, F.; Chan, L. C.; Das, S. K.; Grillot, A.-L.; Bennani, Y. L.; Maxwell, J. P. Biorg. Med. Chem. Lett. 2015, 25, 948. |
| [19] | Lu, X.-Y.; Hu, X.-L.; Liu, Z.-Y.; Zhang, T.-Y.; Wang, R.-B.; Wan, B.-J.; Franzblau, S. G.; You, Q.-D. MedChemComm 2017, 8, 1303. |
| [20] | Costales, A.; Mathur, M.; Ramurthy, S.; Lan, J.; Subramanian, S.; Jain, R.; Atallah, G.; Setti, L.; Lindvall, M.; Appleton, B. A.; Ornelas, E.; Feucht, P.; Warne, B.; Doyle, L.; Basham, S. E.; Aronchik, I.; Jefferson, A. B.; Shafer, C. M. Bioorg. Med. Chem. Lett. 2014, 24, 1592. |
| [21] | An, Y.; Lee, E.; Yu, Y.; Yun, J.; Lee, M. Y.; Kang, J. S.; Kim, W.-Y.; Jeon, R. Bioorg. Med. Chem. Lett. 2016, 26, 3067. |
| [22] | Zhang, J.; Yao, D.-H.; Jiang, Y.-N.; Huang, J.; Yang, S.-L.; Wang, J.-H. Bioorg. Chem. 2017, 72, 168. |
| [23] | Seth, K.; Garg, S. K.; Kumar, R.; Purohit, P.; Meena, V. S.; Goyal, R.; Banerjee, U. C.; Chakraborti, A. K. ACS Med. Chem. Lett. 2014, 5, 512. |
| [24] | Salomé, C.; Ribeiro, N.; Chavagnan, T.; Thuaud, F.; Serova, M.; de Gramont, A.; Faivre, S.; Raymond, E.; Désaubry, L. Eur. J. Med. Chem. 2014, 81, 181. |
| [25] | Lu, X.-Y.; Liu, X.-B.; Wan, B.-J.; Franzblau, S. G.; Chen, L.-L.; Zhou, C.-L.; You, Q.-D. Eur. J. Med. Chem. 2012, 49, 164. |
/
| 〈 |
|
〉 |
