Abstract
We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50 = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.
| Original language | English |
|---|---|
| Pages (from-to) | 140-144 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2016 Jan 1 |
Fingerprint
Keywords
- Antagonist
- Metabotropic glutamate receptor
- Molecular docking
- Picolinamides
- Thiazole-2-carboxamides
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Molecular Biology
- Molecular Medicine
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science
Cite this
Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists. / Vu, Hoang Nam; Kim, Ji Young; Hassan, Ahmed H E; Choi, Kihang; Park, Jong Hyun; Park, Ki Duk; Lee, Jae Kyun; Pae, Ae Nim; Choo, Hyunah; Min, Sun Joon; Cho, Yong Seo.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 1, 01.01.2016, p. 140-144.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists
AU - Vu, Hoang Nam
AU - Kim, Ji Young
AU - Hassan, Ahmed H E
AU - Choi, Kihang
AU - Park, Jong Hyun
AU - Park, Ki Duk
AU - Lee, Jae Kyun
AU - Pae, Ae Nim
AU - Choo, Hyunah
AU - Min, Sun Joon
AU - Cho, Yong Seo
PY - 2016/1/1
Y1 - 2016/1/1
N2 - We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50 = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.
AB - We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50 = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.
KW - Antagonist
KW - Metabotropic glutamate receptor
KW - Molecular docking
KW - Picolinamides
KW - Thiazole-2-carboxamides
UR - http://www.scopus.com/inward/record.url?scp=84949500511&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949500511&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2015.11.012
DO - 10.1016/j.bmcl.2015.11.012
M3 - Article
C2 - 26598462
AN - SCOPUS:84949500511
VL - 26
SP - 140
EP - 144
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 1
ER -