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Chemical Structure| 72087-21-9 Chemical Structure| 72087-21-9

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Chemical Structure| 72087-21-9

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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 [ 72087-21-9 ]

CAS No. :72087-21-9
Formula : C7H8N2O
M.W : 136.15
SMILES Code : O=CC1=CN=C(NC)C=C1
MDL No. :MFCD09607923

Safety of [ 72087-21-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501
 

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