Lipophilicity

Lipophilicity can be used to estimate blood-brain barrier permeability in PET (brain) biomarker development.

Dishino, D. D.; Welch, M. J.; Kilbourn, M. R.; Raichle, M. E. "Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals" J Nucl Med 1983, 24, 1030-8.

Waterhouse, R. N.; Mardon, K.; Giles, K. M.; Collier, T. L.; O'Brien, J. C. "Halogenated 4-(Phenoxymethyl)piperidines as Potential Radiolabeled Probes for σ-1 Receptors:  In Vivo Evaluation of [123I]-1-(Iodopropen-2-yl)-4-[(4-cyanophenoxy)methyl]piperidine" J Med Chem 1997, 40, 1657-67 and references therein.  (Lipophilicity estimation: LogP 7.5 value is determined by reverse-phase HPLC with non-radioactive 'cold' compounds)

Wilson, A. A.; Jin, L.; Garcia, A.; DaSilva, J. N.; Houle, S. "An admonition when measuring the lipophilicity of radiotracers using counting techniques" Appl Radiat Isot 2001, 54, 203-8.  (also known as, "Pre-washing Shake flask" method; A radiolabeled compound is necessary for the determination of lipophilicity.)

Waterhouse, R. N. "Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents" Mol Imaging Biol 2003, 5, 376-89. (Review)

Pike, V. W. "PET radiotracers: crossing the blood-brain barrier and surviving metabolism" Trends Pharmacol Sci 2009, 30, 431-40. (Review)

Zoghbi, S. S.; Anderson, K. B.; Jenko, K. J.; Luckenbaugh, D. A.; Innis, R. B.; Pike, V. W. "On Quantitative Relationships Between Drug-Like Compound Lipophilicity and Plasma Free Fraction in Monkey and Human" J Pharm Sci 2012, 101, 1028-39.

Lipophilicity prediction

http://www.molinspiration.com/cgi-bin/properties