2. Academic Validation
  3. Enterovirus inhibitory activity of C-8-tert-butyl substituted 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-ones

Enterovirus inhibitory activity of C-8-tert-butyl substituted 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-ones

  • Bioorg Med Chem Lett. 2017 Aug 1;27(15):3582-3585. doi: 10.1016/j.bmcl.2017.05.030.
Bishyajit Kumar Biswas 1,  Yashwardhan R Malpani 1,  Neul Ha 1,  Do-Hyun Kwon 2,  Jin Soo Shin 2,  Hae-Soo Kim 2,  Chonsaeng Kim 2,  Soo Bong Han 1,  Chong-Kyo Lee 2,  Young-Sik Jung 3
Affiliations

Affiliations

  • 1 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeongro, Yuseong, Daejeon 34114, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, 217 Gajeongro, Yuseong, Daejeon 34113, Republic of Korea.
  • 2 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeongro, Yuseong, Daejeon 34114, Republic of Korea.
  • 3 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeongro, Yuseong, Daejeon 34114, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, 217 Gajeongro, Yuseong, Daejeon 34113, Republic of Korea. Electronic address: ysjung@krict.re.kr.
PMID: 28587824 DOI: 10.1016/j.bmcl.2017.05.030
Abstract

Members of a series of 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-ones (1, Fig. 2) were prepared and tested against representative enteroviruses including Human Coxsackievirus B1 (COX B1), Human Coxsackievirus B3 (COX B3), human Poliovirus 3 (PV3), human Rhinovirus 14 (HRV14), human Rhinovirus 21 (HRV 21) and human Rhinovirus 71 (HRV 71). The C-8-tert-butyl group on the tetrahydrobenzene ring in these substances was found to be crucial for their Enterovirus activity. One member of this group, 1e, showed single digit micromolar activities (1.6-8.85μM) against a spectrum of viruses screened, and the highest selectivity index (SI) values for COX B1 (>11.2), for COX B3 (>11.5), and for PV3 (>51.2), respectively. In contrast, 1p, was the most active analog against the selected HRVs (1.8-2.6μM), and showed the highest selectivity indices among the group of compounds tested. The SI values for 1p were 11.5 for HRV14, 8.4 for HRV21, and 12.1 for HRV71, respectively.

Keywords

4-Aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e]triazolo[4,3-a]pyrimidin-5(4H)-one Poliovirus; Antiviral; Enterovirus; Rhinovirus.

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