Abstract
Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.
| Original language | English |
|---|---|
| Pages (from-to) | 4806-4809 |
| Number of pages | 4 |
| Journal | Bioorganic & Medicinal Chemistry Letters |
| Volume | 19 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - 15 Aug 2009 |
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Keywords
- β-Diketo
- HIV-1
- Integrase inhibitors
- Quinolinone
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Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor. / Vandurm, Pierre; Cauvin, Christine; Guiguen, Allan; Georges, Benoît; Van, Kiet Le; Martinelli, Valérie; Cardona, Christelle; Mbemba, Gladys; Mouscadet, Jean François; Hevesi, László; Lint, Carine Van; Wouters, Johan.
In: Bioorganic & Medicinal Chemistry Letters, Vol. 19, No. 16, 15.08.2009, p. 4806-4809.Research output: Contribution to journal › Article
TY - JOUR
T1 - Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor
AU - Vandurm, Pierre
AU - Cauvin, Christine
AU - Guiguen, Allan
AU - Georges, Benoît
AU - Van, Kiet Le
AU - Martinelli, Valérie
AU - Cardona, Christelle
AU - Mbemba, Gladys
AU - Mouscadet, Jean François
AU - Hevesi, László
AU - Lint, Carine Van
AU - Wouters, Johan
PY - 2009/8/15
Y1 - 2009/8/15
N2 - Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.
AB - Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.
KW - β-Diketo
KW - HIV-1
KW - Integrase inhibitors
KW - Quinolinone
UR - http://www.scopus.com/inward/record.url?scp=67651091690&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2009.06.044
DO - 10.1016/j.bmcl.2009.06.044
M3 - Article
C2 - 19556126
AN - SCOPUS:67651091690
VL - 19
SP - 4806
EP - 4809
JO - Bioorganic and medicinal chemistry letters
JF - Bioorganic and medicinal chemistry letters
SN - 0960-894X
IS - 16
ER -