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2-Methylacrylamide as a bioisoster of thiourea group for 1,3-dibenzylthioureido TRPV1 receptor antagonists.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Jun2018, Vol. 28 Issue 11, p2080-2083. 4p. - Publication Year :
- 2018
-
Abstract
- In order to replace thiourea group with the more drug-like moiety for 1,3-dibenzylthioureas having TRPV1 antagonist activity, we introduced a set of functional groups between the two aromatic rings based on bioisosteric replacement. The synthesized bioisosteres of 1,3-dibenzylthioureas were tested for their antagonist activities on TRPV1 by 45 Ca 2+ -influx assay using neonatal rat cultured spinal sensory neurons. Among the tested 14 kinds of bioisosters, 2-methylacrylamide group was the best candidate to replace thiourea group. Compound 7c , 2-methylacrylamide analog of ATC-120, showed as potent as ATC-120 in its antagonist activity. In addition, 2-methylacrylamide analog 7e having vinyl moiety showed the most potent activity with 0.022 μM of IC 50 value, indicating that thiourea group of 1,3-dibenzylthioureas could be replaced to 2-methylacrylamide without loss of their potencies. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 28
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 129682515
- Full Text :
- https://doi.org/10.1016/j.bmcl.2018.04.044