Library of novel small molecules with high CNS MPO scores
47 360 compounds
To create the CNS-targeted library that will enable discovery of new CNS drugs we employed versatile approaches, bearing in mind molecular properties and structural features preferable for BBB permeability.
We have carefully selected diverse compounds with desirable CNS properties. All compounds are stored as dry materials and they can be acquired in diverse custom formats. Alternatively, we can supply a copy of plated CNS Library, that can be also made in a customized ready-to-screen formats. Using our CNS Library for hit discovery you receive multiple benefits allowing you to save on time and costs in lead generation:
- Analogs and hit samples resupply from dry stock of over 4.5M compounds.
- Straightforward & low-cost synthesis of follow-up libraries through our REAL Database technology
- Medicinal chemistry support enhanced with on-site broad ADME/T panel
You have also an option to screen the library directly at Enamine. In this case we will be happy to offer you discount on library cost depending on the collaboration scope.
Typical Formats
CNS Library is available for supply in various pre-plated formats, including the following most popular ones:
Catalog No.
CNS-47-0-Z-10
Compounds
47 360
37 plates
Amount
≤ 300 nL of 10 mM of DMSO solutions
Plates and formats
1536-well Echo LDV microplates, first and last four columns empty, 1280 compounds per plate
Price
Catalog No.
CNS-47-10-Y-10
Compounds
47 360
148 plates
Amount
≤ 10 µL of 10 mM DMSO solutions
Plates and formats
384-well, Echo Qualified LDV microplates #001-12782 (LP-0200), first and last two columns empty, 320 compounds per plate
Price
Catalog No.
CNS-47-50-Y-10
Compounds
47 360
148 plates
Amount
50 μL of 10 mM DMSO solutions
Plates and formats
384-well, Greiner Bio-One plates #781280, 1,2 and 23,24 columns empty, 320 compounds per plate
Price
Catalog No.
Library & follow-up package
Plates and formats
CNS-47-10-Y-10 screening library 47 360 cmpds, hit resupply, analogs from 4.4M+ stock and synthesis from REAL Space
Price
*We will be happy to provide our library in any other most convenient for your project format. Please select among the following our standard microplates: Greiner Bio-One 781270, 784201, 781280, 651201 or Echo Qualified 001-12782 (LP-0200), 001-14555 (PP-0200), 001-6969 (LP-0400), C52621 or send your preferred labware. Compounds pooling can be provided upon request.
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Library design
Overcoming the difficulty of delivering therapeutic agents to the specific CNS sites is one of the major challenges in discovery of new treatments of neurological disorders. The criteria for selection of CNS-active molecules which are able to penetrate blood-brain barrier (BBB) were low polar surface area (TPSA < 70 Å2 (median value 48 Å2), cf. 45 Å2 for the marketed CNS drugs), low degree of possible hydrogen bond formation (total number of hydrogen bond acceptors and donors are less than 8) and low ClogP values (average is 1.63). Further selection was driven by evaluation of CNS MPO desirability scores for each candidate compound.
The parameters for selection included:
CNS MPO ≥ 4 (ClogP, ClogD, MW, TPSA, HBD, and pKa for most basic center)
MW ≤ 350 (median value 283, cf. 305 for the marketed CNS drugs),
ClogP ≤ 3.0 (mean value 1.63, cf. 2.8 for the marketed CNS drugs),
Amide groups ≤ 1, HBD ≤ 2, QProp CNS value > 0.
Parameter
MW
Range
170 ... 350
Parameter
RotBonds
Range
≤ 4
Parameter
ClogP
Range
-0.5 ... 3.0
Parameter
Aromatic rings
Range
1 ... 3
Parameter
HBD
Range
≤ 2
Parameter
Fsp3
Range
0.15 ... 0.8
Parameter
TPSA
Range
≤ 70 Å2
Parameter
QPPCaco-2
Range
> 500
Parameter
Amide groups
Range
≤ 1
Parameter
Basic N
Range
≤ 2
Parameter
Total H-bonding
Range
< 8
Parameter
QPlogBB
Range
-1.0-0.8
Parameter
Carboxylic acids
Range
≤ 1
Parameter
CNS
Range
> 0
Parameter
CNS MPO
Range
≥ 4
Parameter
pKa_bs
Range
-1.5 ... 8.0
Key features
Modern CNS drug discovery notions suggest that conformational constraints and rigidity of the molecules are important structural features of CNS-active compounds. Our selection of CNS compounds was enriched with recently synthesized molecules having sp3-rich saturated ring cores of various architectures including spirocyclic (1 341 compounds, 14.5%), bridged and fused scaffolds (4 106 compounds, 44.5%).
Novelty
Compounds included into CNS focused Library were selected from all three screening collections - HTS, Advanced and Premium. Preference was given to the compounds synthesized within the last 4 years, based on innovative scaffolds and with use of advanced building blocks to enhance the novelty value of the library.
Molecular properties
