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Chemical Structure| 129113-00-4

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Hurtle, Bryan T ; Jana, Susovan ; Cai, Lisheng ; Pike, Victor W ;

Abstract: Ligand-based virtual screening (LBVS) has rarely been tested as a method for discovering new structural scaffolds for PET radioligand development. This study used LBVS to discover potential chemotype leads for developing radioligands for PET imaging of tauopathies. ZINC12, a free database of over 12 million commercially available compounds, was searched to discover novel scaffolds based on similarities to four query compounds. Thirteen high-ranking hits were purchased and assayed for their ability to compete against three tritiated radioligands at their distinct binding sites in Alzheimer’s disease brain tissue. Three hits were 2-substituted 6-methoxy naphthalenes. Synthetic elaboration of this new chemotype yielded three new ligands (25, 26, and 28) with high affinity for the [3H]6 (flortaucipur) neurofibrillary tangle binding site. Compound 28 showed remarkably high affinity (Ki, 7 nM) and other desirable properties for a candidate PET radioligand, including low topological polar surface area, moderate computed log D, and amenability for labeling with carbon-11. LBVS appears to be uniquely valuable for discovering new chemotypes for candidate PET radioligands.

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Product Details of [ 129113-00-4 ]

CAS No. :129113-00-4
Formula : C13H10O
M.W : 182.22
SMILES Code : COC1=CC2=CC=C(C#C)C=C2C=C1
MDL No. :MFCD00089947

Safety of [ 129113-00-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H318-H410
Precautionary Statements:P273-P280-P305+P351+P338
Class:9
UN#:3077
Packing Group:
 

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