Pd-Catalyzed Synthesis of Piperazine Scaffolds Under Aerobic and Solvent-Free Conditions

A facile Pd-catalyzed methodology providing an efficient synthetic route to biologically relevant arylpiperazines under aerobic conditions is reported. Electron donating and sterically hindered aryl chlorides were aminated to afford yields up to 97%, with examples using piperazine as solvent, illustrating an ecofriendly, cost-effective synthesis of these privileged structures

Rapid Cu-Catalyzed [²¹¹At]Astatination and [¹²⁵I]Iodination of Boronic Esters at Room Temperature

Access to ²¹¹At- and ¹²⁵I-radiolabeled compounds in excellent RCCs and RCYs was achieved in just 10 min at room temperature using a Cu catalyst. The reaction conditions are applicable to a broad class of aryl and heteroaryl boronic reagents with varying steric and electronic properties as well as late-stage astatination and iodination of anticancer PARP inhibitors. This protocol eliminates the traditional need for toxic organotin reagents, elevated temperatures, and extended reaction times, providing a more practical and environmentally friendly approach to developing α-emitting radiotherapeutics

Chemical structures of [³H]WC-10 and [³H]raclopride.

<p><i>K_d</i> values were obtained through saturation binding of [³H]<b>WC-10</b> and [³H]raclopride to cloned human D₃ and D_2L receptors expressed in HEK cells. a₁, and b₁ represent the fractional receptor occupancy to dopamine D₂ and D₃ receptors in human brain at a ligand concentration of 3.54 nM for [³H]<b>WC-10</b>. a₂ and b₂ represent the same parameters at a ligand concentration of 2.50 nM [³H]raclopride. The receptor occupancy fractions were calculated from the saturation binding isotherm using the <i>K_d</i> values. *Data were taken from Xu et al. (2009).</p

Dopamine D₁, D₂, D₃ receptors, dopamine transporter (DAT) and vesicular monoamine transporter type-2 (VMAT2) densities and D₂ ∶ D₃ receptor density ratio in aged human brain.

<p>Receptor densities (fmol/mg) presented as mean value ±SEM.</p

Comparison of dopamine D₁, D₂, and D₃ receptors, and DAT and DTBZ densities in the striatal regions between an aged rhesus monkey (25 years old) and aged human brain samples.

<p>Autoradiograms show neuroanatomical localization of [³H]SCH23390 for D₁, [³H]raclopride for D₂, [³H]<b>WC-10</b> for D₃ receptors, [³H]WIN35428 for DAT and [³H]DTBZ for VMAT2 in the striatal regions of rhesus monkey (A) and aged human brain (B). [³H]Microscale stnadards (ranging from 0 to 36.3 nCi/mg) (C). The numbers 1 through 8 in panels (A) (B) designate the following CNS anatomical regions: 1: Monkey putamen; 2: Monkey caudate; 3: Monkey globus pallidus; 4: Monkey thalamus; 5: Human putamen; 6: Human caudate; 7: Human globus pallidus; 8: Human thalamus.</p

Correlation of DAT with VMAT2 in the striatal regions and substantia nigra.

<p>The correlation between the VMAT2 and DAT densities in the precommissural putamen (PrePu), caudate (PreCd) and substantia nigra (SN) (A). Correlation of the VMAT densities between the substantia nigra (SN) and PrePu or PreCd (B). Correlation of the DAT densities between the SN and PrePu or PreCd (C). The average VMAT DAT density ratio in the PrePu, PreCd and SN (D). #p<0.01 compared to SN.</p

Quantitative autoradiographic analysis of dopamine receptors, DAT and DTBZ densities in the thalamus.

<p>Autoradiograms show total binding of 1.44 nM [³H]SCH23390, 2.50 nM [³H]raclopride, 3.54 nM [³H]<b>WC-10</b>, 2.19 nM [³H]WIN35428, 4.53 nM [³H]DTBZ (A), and nonspecific binding in presence of 1 µM (+) butaclamol (for [³H]SCH23390), 1 µM <i>S</i>(-)-eticlopride (for [³H]raclopride and [³H]<b>WC-10</b>), 1 µM nomifensine (for WIN35428) and 1 µM <i>S</i>(-)-tetrabenazine (for DTBZ) (B) in the thalamus of human brain sections. The adjacent section shows cresyl violet staining to identify related anatomical structures (C). [³H]Microscale standards (ranging from 0 to 36.3 nCi/mg) were also counted (D). Quantitative analysis of dopamine D₁, D₂, and D₃ receptors, DAT and DTBZ densities (fmol/mg) and the dopamine D₂ ∶ D₃ receptor density ratio in human brain are shown in E and F, respectively. Linear correlation analysis of the average dopamine D₁ and D₃ receptor densities in human thalamus is shown in (G). The numbers 1 through 4 designate the following CNS anatomical regions: 1: Postcommissural putamen (PostPu); 2: Postcommissural caudate (PosCd); 3: Thalamus; 4: Internal capsule (IC). #p<0.01 compared to thalamus.</p

Quantitative autoradiographic analysis of dopamine D₃ receptors, DAT and DTBZ densities in the globus pallidus.

<p>Autoradiograms show total binding of 1.44 nM [³H]SCH23390, 2.50 nM [³H]raclopride, 3.54 nM [³H]<b>WC-10</b>, 2.19 nM [³H]WIN35428, 4.53 nM [³H]DTBZ (A), and nonspecific binding in presence of 1 µM (+) butaclamol (for [³H]SCH23390), 1 µM <i>S</i>(-)-eticlopride (for [³H]raclopride and [³H]<b>WC-10</b>), 1 µM nomifensine (for [³H]WIN35428) and 1 µM <i>S</i>(-)-tetrabenazine (for [³H]DTBZ) (B) in the globus pallidus of aged human brain sections. The adjacent section shows cresyl violet staining to identify related anatomical structures (C). [³H]Microscale standards (ranging from 0 to 36.3 nCi/mg) were also counted (D). Quantitative analysis of dopamine D₁, D₂, and D₃ receptors, DAT and DTBZ densities (fmol/mg) and the dopamine D₂ ∶ D₃ receptor density ratio in human globus pallidus are shown in E and F, respectively. The numbers 1 through 5 designate the following CNS anatomical regions: 1: Putamen; 2: Caudate; 3: Globus pallidus external part (GPe); 4: Globus pallidus internal part (GPi); 5: Internal capsule (IC). *p<0.05 compared to GPe.</p

Comparison of dopamine D₁, D₂, D₃ receptors, DAT and VMAT2 densities (fmol/mg) in the striatal regions of adult rhesus monkey and aged human brain.

<p>Data were obtained from 10 aged healthy human and a 25 years old rhesus monkey brain and presented as mean value ± stdev. Pu: Putamen; Cd: Caudate.</p

Quantitative autoradiographic analysis of dopamine receptors, and DAT and DTBZ densities in the substantia nigra.

<p>Autoradiograms show total binding of 1.44 nM [³H]SCH23390, 2.50 nM[³H]raclopride, 3.54 nM [³H]<b>WC-10</b>, 2.19 nM [³H]WIN35428, 4.53 nM [³H]DTBZ (A), and nonspecific binding in presence of 1 uM (+) butaclamol (for [³H]SCH23390), 1 µM <i>S</i>(-)-eticlopride (for [³H]raclopride and [³H]<b>WC-10</b>), 1 µM nomifensine (for WIN35428) and 1 µM <i>S</i>(-)-tetrabenazine (for DTBZ) (B) in the substantia nigra (SN) of aged human brain sections. [³H]Microscale standards (ranging from 0 to 36.3 nCi/mg) were also counted (C). Quantitative analysis of dopamine D₁, D₂ and D₃ receptors, and DAT and DTBZ densities (fmol/mg) and the dopamine D₂ ∶ D₃ receptor density ratio in human SN and red nucleus are shown in D and E respectively. The numbers 1 through 3 designate the following CNS anatomical regions: 1: Substantia nigra (SN); 2: Red nucleus (RN); 3: Thalamus.</p