The Synthesis and Initial Evaluation of MerTK Targeted PET Agents

MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to MerTK suppression may not be uniform due to the heterogeneity of solid tumors and different tumor stages. In this report, we develop a series of radiolabeled agents as potential MerTK PET (positron emission tomography) agents. In our initial in vivo evaluation, [18F]-MerTK-6 showed prominent uptake rate (4.79 ± 0.24%ID/g) in B16F10 tumor-bearing mice. The tumor to muscle ratio reached 1.86 and 3.09 at 0.5 and 2 h post-injection, respectively. In summary, [18F]-MerTK-6 is a promising PET agent for MerTK imaging and is worth further evaluation in future studies

Organocatalytic Asymmetric Synthesis of α‑Oxetanyl and α‑Azetidinyl Tertiary Alkyl Fluorides and Chlorides

Asymmetric thiourea and squaramide catalysis provides access to synthetically versatile α-oxetanyl and α-azetidinyl alkyl halides exhibiting a tetrasubstituted chiral carbon center with high yields and enantioselectivities. The products are readily transformed with negligible erosion of enantiopurity and excellent diastereoselectivity to a diverse group of multifunctional compounds including fluorooxindoles with two contiguous chirality centers, fluorinated heterocyclic spiranes, and polyspiro compounds

Organocatalytic Insertion of Isatins into Aryl Difluoronitromethyl Ketones

An organocatalytic method that achieves insertion of isatins into aryl difluoro­nitro­methyl ketones under mild conditions is described. The reaction occurs in the presence of 20 mol % of DBU and with 100% atom economy. A series of isatin derived difluoro­nitro­methyl substituted tertiary alcohol benzoates and naphthoates were prepared in 81–99% yield. The general synthetic usefulness of these 3-hydroxy­oxindole derivatives is demonstrated with the selective reduction to fluorooximes

The Synthesis and Initial Evaluation of MerTK Targeted PET Agents

MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to MerTK suppression may not be uniform due to the heterogeneity of solid tumors and different tumor stages. In this report, we develop a series of radiolabeled agents as potential MerTK PET (positron emission tomography) agents. In our initial in vivo evaluation, [18F]-MerTK-6 showed prominent uptake rate (4.79 ± 0.24%ID/g) in B16F10 tumor-bearing mice. The tumor to muscle ratio reached 1.86 and 3.09 at 0.5 and 2 h post-injection, respectively. In summary, [18F]-MerTK-6 is a promising PET agent for MerTK imaging and is worth further evaluation in future studies