CNS

Life Chemicals CNS library comprises over 22,700 carefully designed and diverse small organic molecules. Compounds for this library have been selected according to the steps listed below. Calculations were done in SYBYL-X and VolSurf+ software:

1. Life chemicals in-stock compound collection has been filtered to meet the following criteria:

MW ≤ 450
ClogP ≤ 3.6
H-Bond Acceptors ≤ 8
H-Bond Donors ≤ 5
TPSA ≤ 120
Rotatable Bonds ≤ 5
logBB -3.0 to 1.0

2. PAIN and ADME filters were applied.
3. CNS specific filters applied:

a) If N + O ≤ 5 then the compound has a high chance to cross blood-brain barrier1.
b) If ClogP – (N+O)>0 then LogBB is likely to be positive1.
c) MW should be kept below 450 to facilitate CNS permeation2.
d) CNS drugs tend to be more rigid (caused by lack of rotable bonds) compared to non CNS drugs3.

According to4, compounds with logBB > 0.3 are readily distributed to the brain, while compounds with logBB < -1.00 are poorly distributed to the brain. The implemented filter removes compounds with logBB <= 0.3. In addition to that it also removes salts and zwitterions. This approach can only predict BBB penetration of compounds in the absence of active transport.

Finally, substructure filters for detection and removal of Pan Assay Interference (PAINS) compounds have been applied.


References
1. Norinder, U. and Haeberlein, M. (2002). Computational approaches to the prediction of blood brain distribution. Adv. Drug Deliv. Rev. 54, 291-313
2. Van de Waterbeemd, H. et al. (1998). Estimation of blood-brain barrier crossing of drugs using molecular size and shape and H-bonding descriptors. J, Drug Target. 6, 151-165
3. Doan, K.M. et al. (2002). Passive permeability and P-glycoprotein mediated efflux differentiate central nervous system (CNS) and non CNS marketed drugs. J. Pharmacol. Exp. Ther. 303, 1029-1037
4. Abraham MH, Takács-Novák K, Mitchell RC. On the partition of ampholytes: application to blood-brain distribution. J Pharm Sci. 1997 Mar;86(3):310-5.