2122
J. Med. Chem. 2002, 45, 2122
Additions and Corrections 2001, Volume 44 Jay T. Goodwin, Robert A. Conradi, Norman F. H. Ho, and Philip S. Burton*: Physicochemical Determinants of Passive Membrane Permeability: Role of Solute Hydrogen-Bonding Potential and Volume. Page 3722. In line 25, “... from log Phydrocarbon/water log Poctanol/water...” should be “... from log Poctanol/water log Phydrocarbon/water...”. In Table 1, the values for log ptrans should be negative in sign. Page 3733. In Table 2, the values for log Poctanol/water for compounds 1 and 2, all values of log Phydrocarbon/water, and all values of log Pheptane/glycol should be negative in sign. Table 1. Permeability Data for Compounds 1-12 peff compound
AP f BLa
BL f APa
ratiob
1 2 3a 4 5a 6 7 8 9a 10 11a 12
0.17 0.24 0.91 1.41 2.75 7.20 21.9 24.6 34.5 42.6 52.0 58.3
0.24 0.38 1.84 2.24 5.19 14.5 20.6 22.9 32.4 47.2 56.8 58.4
1.4 1.6 2.0 1.6 1.9 2.0 0.9 0.9 0.9 1.1 1.1 1.0
peff,verapamil AP f BLa BL f APa 0.14 0.25 0.89 1.52 2.80 8.93 22.6 25.2 35.1 47.4 55.1 55.5
0.12 0.25 0.78 1.42 2.64 9.02 20.8 23.5 33.0 47.7 59.5 55.6
ratiob
pmonoc
pparac
ptransc
log ptrans
0.9 1.0 0.9 0.9 0.9 1.0 0.9 0.9 0.9 1.0 1.1 1.0
0.14 0.25 0.9 1.56 2.95 10.7 38.4 46.5 97.0 343
0.60 0.56 0.48 0.44 0.37 0.36 0.77 0.71 0.60 0.56
0.00 0.00 0.42 1.12 2.58 10.3 37.6 45.8 96.4 342
-6.38 -5.95 -5.59 -4.99 -4.42 -4.34 -4.02 -3.47
a AP f BL ) apical-to-basolateral permeability; BL f AP ) basolateral-to-apical permeability. b Ratio of BL f AP to AP f BL permeabilities. c pmono ) monolayer permeability, ppara ) paracellular permeability, ptrans ) transcellular permeability; permeabilities are given in units of 10-6 centimeters per second. Standard errors in permeabilities are e10%, n g 4, except for compounds 7, 8, 9a, and 10, where the standard error is e30%. The mass balances for all permeabilities determined are 100% ((10%).
Table 2. Physicochemical Data for Compounds 1-12 compound
MW
tHBa
dHBa
aHBa
log Poctanol/waterb
log Pheptane/waterb
∆ log Pb
log Pheptane/glycolb
1 2 3a 4 5a 6 7 8 9a 10 11a 12
277 291 319 333 367 373 220 234 262 276 310 316
6 6 6 6 6 6 4 4 4 4 4 4
3 3 3 3 3 3 2 2 2 2 2 2
3 3 3 3 3 3 2 2 2 2 2 2
-0.30 -0.06 0.66 1.24 1.44 2.40 0.48 0.76 1.59 2.03 2.32 3.13
-6.30 -6.26 -5.33 -4.61 -4.15 -3.41 -3.73 -3.53 -2.64 -2.14 -2.00 -0.90
6.00 6.20 5.99 5.85 5.59 5.81 4.21 4.29 4.23 4.17 4.32 4.03
-6.17 -5.83 -5.79 -5.43 -5.34 -5.03 -5.00 -4.40 -3.77 -3.69 -3.70 -3.41
a tHB ) total number of solute hydrogen bonds possible, dHB ) number of donor hydrogen bonds, aHB ) number of acceptor hydrogen bonds. b Standard error for log Poctanol/water e 15%, for log Pheptane/water e 10%, for ∆ log P e 15%, and for log Pheptane/ethylene glycol e 5%; n g 2 for all solvent partition experiments.
JM0200963 10.1021/jm0200963 Published on Web 04/10/2002
