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Corrigendum to “Activity of novel 4-PIOL analogues at human α1β2γ2S GABAA receptors—correlation with hydrophobicity” [Eur. J. Pharmacol. 451 (2002) 125–132]
European Journal of Pharmacology 453 (2002) 345 – 346 www.elsevier.com/locate/ejphar
Corrigendum
Corrigendum to ‘‘Activity of novel 4-PIOL analogues at human a1h2g2S GABAA receptors—correlation with $ hydrophobicity’’ [Eur. J. Pharmacol. 451 (2002) 125–132] Martin Mortensen a, Bente Frølund b, Anne T. Jørgensen b, Tommy Liljefors b, Povl Krogsgaard-Larsen b, Bjarke Ebert c,* b
a Department of Pharmacology, The Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100 Copenhagen Ø, Denmark Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, 2 Universiteitsparken, DK-2100 Copenhagen Ø, Denmark c Department of Molecular Pharmacology, H. Lundbeck A/S, 9 Otilliavej, DK-2500 Valby, Denmark
Table 1 Estimates of the lipophilicity of 4-PIOL analogue substituents (log P) and antagonist potencies (Ki) obtained by two-electrode voltage clamping on a1h2g2S expressing Xenopus oocytes Compound
log P
Ki (AM) (pKi F SEM)
5 6a 6b 6c 6d 6e 6f 6g 6h 6i 6j 6k 6l 6m 6n 6o 6p 6q
0 1.09 1.26 1.72 2.17 3.09 2.28 2.74 3.19 4.52 3.72 3.40 3.86 3.40 3.86 3.96 4.42 4.87
36 45 10 3.7 3.9 0.66 2.8 6.2 0.80 1.5 0.31 0.099 0.77 0.62 2.3 0.42 0.026 0.12
(4.449 F 0.181) (4.350 F 0.098) (4.984 F 0.059) (5.433 F 0.073) (5.414 F 0.111) (6.178 F 0.081) (5.552 F 0.102) (5.210 F 0.158) (6.096 F 0.150) (5.834 F 0.077) (6.506 F 0.046) (7.005 F 0.132) (6.112 F 0.062) (6.206 F 0.073) (5.636 F 0.027) (6.374 F 0.038) (7.588 F 0.087) (6.936 F 0.043)
The author apologises that in the above-mentioned article, some correlations between log P values were erroneously printed. The correct Table 1, Fig. 7, and corrected texts are given here. p. 129, Section 3.3, paragraph 5, lines 1 –11 should read: As shown in Fig. 6, a linear correlation between pKi and log P values was obtained for the complete data set (r 2 = 0.696, P < 0.001; stippled line; slope 0.540). The correlation between pKi values and log P values of the remaining compounds (Fig. 6, filled circles) showed an excellent correlation (r 2 = 0.918, P < 0.001; unbroken line; slope
The estimates of the logarithm of partition coefficient in n-octanol/water (log P) were obtained by use of Crippen’s fragmentation method (Ghose and Crippen, 1986; Ghose et al., 1988) in the computer programme ChemDraw Ultra 5.0. The antagonist potencies were determined by shifts of agonist concentration – response curves using two-electrode voltage clamping on a1h2g2S expressing Xenopus oocytes (see Materials and methods). Ki values (AM) are calculated from pKi values found in brackets. The pKi values represent mean F S.E.M. of at least four experiments.
$
PII of original article S0014-2999(02)02271-9. * Corresponding author. Tel.: +45-2220-0245; fax: +45-3644-0043. E-mail address: [email protected] (B. Ebert).
Fig. 7. Correlation between the mean antagonist affinity (pKi) and the lipophilicity (log P) of the substituent of the 4-PIOL analogues. The stippled line shows the correlation for all compounds, the two grey lines connect the high affinity compounds (open squares) and the low-affinity compounds (open triangles), respectively, and the black line shows the correlation between the remaining compounds (black circles).
0014-2999/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 0 1 4 - 2 9 9 9 ( 0 2 ) 0 2 4 5 7 - 3
346
Corrigendum
0.551), indicating a common binding mechanism for these compounds (see Discussion). p. 131, Discussion, paragraph 9, lines 14 –19 should read: The fact that the line correlating affinity with lipophilicity of these compounds has a slope of 0.551 indicates
only partial desolvation of the compounds, or in other words, that the four substituents of these ligands when located in the lipophilic binding site are still partly exposed to water (Leo and Hansch, 1999).
Corrigendum
Corrigendum to ‘‘Activity of novel 4-PIOL analogues at human a1h2g2S GABAA receptors—correlation with $ hydrophobicity’’ [Eur. J. Pharmacol. 451 (2002) 125–132] Martin Mortensen a, Bente Frølund b, Anne T. Jørgensen b, Tommy Liljefors b, Povl Krogsgaard-Larsen b, Bjarke Ebert c,* b
a Department of Pharmacology, The Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100 Copenhagen Ø, Denmark Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, 2 Universiteitsparken, DK-2100 Copenhagen Ø, Denmark c Department of Molecular Pharmacology, H. Lundbeck A/S, 9 Otilliavej, DK-2500 Valby, Denmark
Table 1 Estimates of the lipophilicity of 4-PIOL analogue substituents (log P) and antagonist potencies (Ki) obtained by two-electrode voltage clamping on a1h2g2S expressing Xenopus oocytes Compound
log P
Ki (AM) (pKi F SEM)
5 6a 6b 6c 6d 6e 6f 6g 6h 6i 6j 6k 6l 6m 6n 6o 6p 6q
0 1.09 1.26 1.72 2.17 3.09 2.28 2.74 3.19 4.52 3.72 3.40 3.86 3.40 3.86 3.96 4.42 4.87
36 45 10 3.7 3.9 0.66 2.8 6.2 0.80 1.5 0.31 0.099 0.77 0.62 2.3 0.42 0.026 0.12
(4.449 F 0.181) (4.350 F 0.098) (4.984 F 0.059) (5.433 F 0.073) (5.414 F 0.111) (6.178 F 0.081) (5.552 F 0.102) (5.210 F 0.158) (6.096 F 0.150) (5.834 F 0.077) (6.506 F 0.046) (7.005 F 0.132) (6.112 F 0.062) (6.206 F 0.073) (5.636 F 0.027) (6.374 F 0.038) (7.588 F 0.087) (6.936 F 0.043)
The author apologises that in the above-mentioned article, some correlations between log P values were erroneously printed. The correct Table 1, Fig. 7, and corrected texts are given here. p. 129, Section 3.3, paragraph 5, lines 1 –11 should read: As shown in Fig. 6, a linear correlation between pKi and log P values was obtained for the complete data set (r 2 = 0.696, P < 0.001; stippled line; slope 0.540). The correlation between pKi values and log P values of the remaining compounds (Fig. 6, filled circles) showed an excellent correlation (r 2 = 0.918, P < 0.001; unbroken line; slope
The estimates of the logarithm of partition coefficient in n-octanol/water (log P) were obtained by use of Crippen’s fragmentation method (Ghose and Crippen, 1986; Ghose et al., 1988) in the computer programme ChemDraw Ultra 5.0. The antagonist potencies were determined by shifts of agonist concentration – response curves using two-electrode voltage clamping on a1h2g2S expressing Xenopus oocytes (see Materials and methods). Ki values (AM) are calculated from pKi values found in brackets. The pKi values represent mean F S.E.M. of at least four experiments.
$
PII of original article S0014-2999(02)02271-9. * Corresponding author. Tel.: +45-2220-0245; fax: +45-3644-0043. E-mail address: [email protected] (B. Ebert).
Fig. 7. Correlation between the mean antagonist affinity (pKi) and the lipophilicity (log P) of the substituent of the 4-PIOL analogues. The stippled line shows the correlation for all compounds, the two grey lines connect the high affinity compounds (open squares) and the low-affinity compounds (open triangles), respectively, and the black line shows the correlation between the remaining compounds (black circles).
0014-2999/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 0 1 4 - 2 9 9 9 ( 0 2 ) 0 2 4 5 7 - 3
346
Corrigendum
0.551), indicating a common binding mechanism for these compounds (see Discussion). p. 131, Discussion, paragraph 9, lines 14 –19 should read: The fact that the line correlating affinity with lipophilicity of these compounds has a slope of 0.551 indicates
only partial desolvation of the compounds, or in other words, that the four substituents of these ligands when located in the lipophilic binding site are still partly exposed to water (Leo and Hansch, 1999).