Category: 178928-58-0

Foley, Timothy L. published the artcile4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a Potent Inhibitor of Bacterial Phosphopantetheinyl Transferase That Attenuates Secondary Metabolism and Thwarts Bacterial Growth, Formula: C11H13N3, the publication is Journal of Medicinal Chemistry (2014), 57(3), 1063-1078, database is CAplus and MEDLINE.

4′-Phosphopantetheinyl transferases (PPTases) catalyze a post-translational modification essential to bacterial cell viability and virulence. We present the discovery and medicinal chem. optimization of 2-pyridinyl-N-(4-aryl)-piperazine-1-carbothioamides, which exhibit submicromolar inhibition of bacterial Sfp-PPTase with no activity toward the human orthologue. Moreover, compounds within this class possess antibacterial activity in the absence of a rapid cytotoxic response in human cells. An advanced analog of this series, ML267 (55), was found to attenuate production of an Sfp-PPTase-dependent metabolite when applied to Bacillus subtilis at sublethal doses. Addnl. testing revealed antibacterial activity against methicillin-resistant Staphylococcus aureus, and chem. genetic studies implicated efflux as a mechanism for resistance in Escherichia coli. Addnl., we highlight the in vitro absorption, distribution, metabolism, and excretion and in vivo pharmacokinetic profiles of compound 55 to further demonstrate the potential utility of this small-mol. inhibitor.

Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Formula: C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Kumar, Vivek published the artcileSynthesis and Pharmacological Characterization of Novel trans-Cyclopropylmethyl-Linked Bivalent Ligands That Exhibit Selectivity and Allosteric Pharmacology at the Dopamine D₃ Receptor (D₃R), Safety of 1-(3-Cyanophenyl)piperazine, the publication is Journal of Medicinal Chemistry (2017), 60(4), 1478-1494, database is CAplus and MEDLINE.

The development of bitopic ligands directed toward D₂-like receptors has proven to be of particular interest to improve the selectivity and/or affinity of these ligands and as an approach to modulate and bias their efficacies. The structural similarities between dopamine D₃ receptor (D₃R)-selective mols. that display bitopic or allosteric pharmacol. and those that are simply competitive antagonists are subtle and intriguing. Herein the authors synthesized a series of mols. in which the primary and secondary pharmacophores were derived from the D₃R-selective antagonists SB269,652 and SB277011A whose structural similarity and pharmacol. disparity provided the perfect templates for SAR investigation. Incorporating a trans-cyclopropylmethyl linker between pharmacophores and manipulating linker length resulted in the identification of two bivalent noncompetitive D₃R-selective antagonists, I and II, which further delineates SAR associated with allosterism at D₃R and provides leads toward novel drug development.

Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Safety of 1-(3-Cyanophenyl)piperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Sun, Aiming published the artcileDiscovering Small-Molecule Estrogen Receptor ¦Á/Coactivator Binding Inhibitors: High-Throughput Screening, Ligand Development, and Models for Enhanced Potency, Product Details of C11H13N3, the publication is ChemMedChem (2011), 6(4), 654-666, database is CAplus and MEDLINE.

Small mols., namely coactivator binding inhibitors (CBIs), that block estrogen signaling by directly inhibiting the interaction of the estrogen receptor (ER) with coactivator proteins act in a fundamentally different way to traditional antagonists, which displace the endogenous ligand estradiol. To complement our prior efforts at CBI discovery by de novo design, we used high-throughput screening (HTS) to identify CBIs of novel structure and subsequently investigated two HTS hits by analog synthesis, finding many compounds with low micromolar potencies in cell-based reporter gene assays. We examined structure-activity trends in both series, using induced-fit computational docking to propose binding poses for these mols. in the coactivator binding groove. Anal. of the structure of the ER-steroid receptor coactivator (SRC) complex suggests that all four hydrophobic residues within the SRC nuclear receptor box sequence are important binding elements. Thus, insufficient water displacement upon binding of the smaller CBIs in the expansive complexation site may be limiting the potency of the compounds in these series, which suggests that higher potency CBIs might be found by screening compound libraries enriched with larger mols.

ChemMedChem published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C10H14O, Product Details of C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Hayatshahi, Hamed S. published the artcileFactors Governing Selectivity of Dopamine Receptor Binding Compounds for D2R and D3R Subtypes, Formula: C11H13N3, the publication is Journal of Chemical Information and Modeling (2021), 61(6), 2829-2843, database is CAplus and MEDLINE.

Targeting the D3 dopamine receptor (D3R) is a promising pharmacotherapeutic strategy for the treatment of many disorders. The structure of the D3R is similar to the D2 dopamine receptor (D2R), especially in the transmembrane spanning regions that form the orthosteric binding site, making it difficult to identify D3R selective pharmacotherapeutic agents. Here, the authors examine the mol. basis for the high affinity D3R binding and D3R vs. D2R binding selectivity of substituted phenylpiperazine thiopheneamides. Removing the thiophenearylamide portion of the ligand consistently decreases the affinity of these ligands at D3R, while not affecting their affinity at the D2R. The authors’ long (>10¦Ìs) mol. dynamics simulations demonstrated that both dopamine receptor subtypes adopt two major conformations that the authors refer to as closed or open conformations, with D3R sampling the open conformation more frequently than D2R. The binding of ligands with conjoined orthosteric-allosteric binding moieties causes the closed conformation to populate more often in the trajectories. Also, significant differences were observed in the extracellular loops (ECL) of these two receptor subtypes leading to the identification of several residues that contribute differently to the ligand binding for the two receptors that could potentially contribute to ligand binding selectivity. The authors’ observations also suggest that the displacement of ordered water in the binding pocket of D3R contributes to the affinity of the compounds containing an allosteric binding motif. These studies provide a better understanding of how a bitopic mode of engagement can determine ligands that bind selectively to D2 and D3 dopamine receptor subtypes.

Journal of Chemical Information and Modeling published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Formula: C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Hayatshahi, Hamed S. published the artcileFactors Governing Selectivity of Dopamine Receptor Binding Compounds for D2R and D3R Subtypes, Formula: C11H13N3, the publication is Journal of Chemical Information and Modeling (2021), 61(6), 2829-2843, database is CAplus and MEDLINE.

Targeting the D3 dopamine receptor (D3R) is a promising pharmacotherapeutic strategy for the treatment of many disorders. The structure of the D3R is similar to the D2 dopamine receptor (D2R), especially in the transmembrane spanning regions that form the orthosteric binding site, making it difficult to identify D3R selective pharmacotherapeutic agents. Here, the authors examine the mol. basis for the high affinity D3R binding and D3R vs. D2R binding selectivity of substituted phenylpiperazine thiopheneamides. Removing the thiophenearylamide portion of the ligand consistently decreases the affinity of these ligands at D3R, while not affecting their affinity at the D2R. The authors’ long (>10¦Ìs) mol. dynamics simulations demonstrated that both dopamine receptor subtypes adopt two major conformations that the authors refer to as closed or open conformations, with D3R sampling the open conformation more frequently than D2R. The binding of ligands with conjoined orthosteric-allosteric binding moieties causes the closed conformation to populate more often in the trajectories. Also, significant differences were observed in the extracellular loops (ECL) of these two receptor subtypes leading to the identification of several residues that contribute differently to the ligand binding for the two receptors that could potentially contribute to ligand binding selectivity. The authors’ observations also suggest that the displacement of ordered water in the binding pocket of D3R contributes to the affinity of the compounds containing an allosteric binding motif. These studies provide a better understanding of how a bitopic mode of engagement can determine ligands that bind selectively to D2 and D3 dopamine receptor subtypes.

Journal of Chemical Information and Modeling published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Formula: C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Kumar, Vivek published the artcileSynthesis and Pharmacological Characterization of Novel trans-Cyclopropylmethyl-Linked Bivalent Ligands That Exhibit Selectivity and Allosteric Pharmacology at the Dopamine D₃ Receptor (D₃R), Safety of 1-(3-Cyanophenyl)piperazine, the publication is Journal of Medicinal Chemistry (2017), 60(4), 1478-1494, database is CAplus and MEDLINE.

The development of bitopic ligands directed toward D₂-like receptors has proven to be of particular interest to improve the selectivity and/or affinity of these ligands and as an approach to modulate and bias their efficacies. The structural similarities between dopamine D₃ receptor (D₃R)-selective mols. that display bitopic or allosteric pharmacol. and those that are simply competitive antagonists are subtle and intriguing. Herein the authors synthesized a series of mols. in which the primary and secondary pharmacophores were derived from the D₃R-selective antagonists SB269,652 and SB277011A whose structural similarity and pharmacol. disparity provided the perfect templates for SAR investigation. Incorporating a trans-cyclopropylmethyl linker between pharmacophores and manipulating linker length resulted in the identification of two bivalent noncompetitive D₃R-selective antagonists, I and II, which further delineates SAR associated with allosterism at D₃R and provides leads toward novel drug development.

Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Safety of 1-(3-Cyanophenyl)piperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Sun, Aiming published the artcileDiscovering Small-Molecule Estrogen Receptor ¦Á/Coactivator Binding Inhibitors: High-Throughput Screening, Ligand Development, and Models for Enhanced Potency, Product Details of C11H13N3, the publication is ChemMedChem (2011), 6(4), 654-666, database is CAplus and MEDLINE.

Small mols., namely coactivator binding inhibitors (CBIs), that block estrogen signaling by directly inhibiting the interaction of the estrogen receptor (ER) with coactivator proteins act in a fundamentally different way to traditional antagonists, which displace the endogenous ligand estradiol. To complement our prior efforts at CBI discovery by de novo design, we used high-throughput screening (HTS) to identify CBIs of novel structure and subsequently investigated two HTS hits by analog synthesis, finding many compounds with low micromolar potencies in cell-based reporter gene assays. We examined structure-activity trends in both series, using induced-fit computational docking to propose binding poses for these mols. in the coactivator binding groove. Anal. of the structure of the ER-steroid receptor coactivator (SRC) complex suggests that all four hydrophobic residues within the SRC nuclear receptor box sequence are important binding elements. Thus, insufficient water displacement upon binding of the smaller CBIs in the expansive complexation site may be limiting the potency of the compounds in these series, which suggests that higher potency CBIs might be found by screening compound libraries enriched with larger mols.

ChemMedChem published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C10H14O, Product Details of C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Hayatshahi, Hamed S. published the artcileFactors Governing Selectivity of Dopamine Receptor Binding Compounds for D2R and D3R Subtypes, Formula: C11H13N3, the publication is Journal of Chemical Information and Modeling (2021), 61(6), 2829-2843, database is CAplus and MEDLINE.

Targeting the D3 dopamine receptor (D3R) is a promising pharmacotherapeutic strategy for the treatment of many disorders. The structure of the D3R is similar to the D2 dopamine receptor (D2R), especially in the transmembrane spanning regions that form the orthosteric binding site, making it difficult to identify D3R selective pharmacotherapeutic agents. Here, the authors examine the mol. basis for the high affinity D3R binding and D3R vs. D2R binding selectivity of substituted phenylpiperazine thiopheneamides. Removing the thiophenearylamide portion of the ligand consistently decreases the affinity of these ligands at D3R, while not affecting their affinity at the D2R. The authors’ long (>10¦Ìs) mol. dynamics simulations demonstrated that both dopamine receptor subtypes adopt two major conformations that the authors refer to as closed or open conformations, with D3R sampling the open conformation more frequently than D2R. The binding of ligands with conjoined orthosteric-allosteric binding moieties causes the closed conformation to populate more often in the trajectories. Also, significant differences were observed in the extracellular loops (ECL) of these two receptor subtypes leading to the identification of several residues that contribute differently to the ligand binding for the two receptors that could potentially contribute to ligand binding selectivity. The authors’ observations also suggest that the displacement of ordered water in the binding pocket of D3R contributes to the affinity of the compounds containing an allosteric binding motif. These studies provide a better understanding of how a bitopic mode of engagement can determine ligands that bind selectively to D2 and D3 dopamine receptor subtypes.

Journal of Chemical Information and Modeling published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Formula: C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Hayatshahi, Hamed S. published the artcileFactors Governing Selectivity of Dopamine Receptor Binding Compounds for D2R and D3R Subtypes, Formula: C11H13N3, the publication is Journal of Chemical Information and Modeling (2021), 61(6), 2829-2843, database is CAplus and MEDLINE.

Targeting the D3 dopamine receptor (D3R) is a promising pharmacotherapeutic strategy for the treatment of many disorders. The structure of the D3R is similar to the D2 dopamine receptor (D2R), especially in the transmembrane spanning regions that form the orthosteric binding site, making it difficult to identify D3R selective pharmacotherapeutic agents. Here, the authors examine the mol. basis for the high affinity D3R binding and D3R vs. D2R binding selectivity of substituted phenylpiperazine thiopheneamides. Removing the thiophenearylamide portion of the ligand consistently decreases the affinity of these ligands at D3R, while not affecting their affinity at the D2R. The authors’ long (>10μs) mol. dynamics simulations demonstrated that both dopamine receptor subtypes adopt two major conformations that the authors refer to as closed or open conformations, with D3R sampling the open conformation more frequently than D2R. The binding of ligands with conjoined orthosteric-allosteric binding moieties causes the closed conformation to populate more often in the trajectories. Also, significant differences were observed in the extracellular loops (ECL) of these two receptor subtypes leading to the identification of several residues that contribute differently to the ligand binding for the two receptors that could potentially contribute to ligand binding selectivity. The authors’ observations also suggest that the displacement of ordered water in the binding pocket of D3R contributes to the affinity of the compounds containing an allosteric binding motif. These studies provide a better understanding of how a bitopic mode of engagement can determine ligands that bind selectively to D2 and D3 dopamine receptor subtypes.

Journal of Chemical Information and Modeling published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Formula: C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics