. Author manuscript; available in PMC: 2014 Jul 14.

Published in final edited form as: J Am Chem Soc. 2013 Dec 27;136(1):299–310. doi: 10.1021/ja409801p

Table 1.

Values (MW, clogP, HBA, HBD, PSA, logBB, and −logP_e)^a for ML and 1

Compound	MW	clogP	HBA	HBD	PSA (Å)	logBB	−logP_e	CNS± prediction^b
ML	323	2.57	5	3	68.1	−0.478	4.49 (±0.01)	CNS+
1	174	0.889	3	3	58.6	−0.593	4.70 (±0.01)	CNS+
Lipinski’s rules and others	≤ 450	≤ 5.0	≤ 10	≤ 5	≤ 90	> 3.0 (readily); < −1.0 (poorly)	< 5.4; > 5.7	CNS+; CNS−

MW, molecular weight; clogP, calculated logarithm of the octanol–water partition coefficient; HBA, hydrogen bond acceptor atoms; HBD, hydrogen bond donor atoms; PSA, polar surface area; logBB = −0.0148 × PSA + 0.152 × clogP + 0.139 (logBB > 3.0, readily crosses BBB; logBB < −1.0, poorly distributed to the brain); −logP_e values were determined using the Parallel Artificial Membrane Permeability Assay (PAMPA), and average −logP_e values were then calculated by the PAMPA 9 Explorer software v. 3.5.

Prediction of a compound’s ability to penetrate the central nervous system (CNS) on the basis of literature values. Compounds categorized as CNS+ possess the ability to penetrate the BBB and are available in the CNS. Compounds assigned as CNS− have poor permeability through the BBB; therefore, their bioavailability into the CNS is considered to be minimal.