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Glidewell Christopher - One of the best experts on this subject based on the ideXlab platform.
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Two N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides as disordered ethanol monosolvates
'International Union of Crystallography (IUCr)', 2020Co-Authors: Harish Chinthal Chayanna, Yathirajan H. S., Kadambar, Anish Kumar, Kalluraya Balakrishna, Foro Sabine, Glidewell ChristopherAbstract:Two new N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides have been prepared by acid-promoted condensation reactions between 3-aryl-4-formylsydnones and N-[(4-amino-5-sulfanylidene-1H-1,2,4-triazol-3-yl)methyl]benzamide, and both have been crystallized as ethanol monosolvates. N-{[4-(3-Phenyl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamide ethanol monosolvate, C19H15N7O3S·C2H6O (I), and N-({4-[3-(4-methylphenyl)-4-sydnonylideneamino]-5-sulfanylidene-1H-1,2,4-triazol-3-yl}methyl)benzamide ethanol monosolvate, C20H17N7O3S·C2H6O (II), differ only in the presence of a methyl group for (II) instead of a hydrogen atom for (I), and in both of them the ethanol component is disordered over two sets of atomic sites having occupancies of 0.836 (6) and 0.164 (6) in (I), and 0.906 (6) and 0.094 (6) in (II). Combinations of O—H⋯O and N—H⋯O hydrogen bonds link the molecules into cyclic, centrosymmetric four-molecule aggregates. Comparisons are made with the structures of some related compounds
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Two N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides as disordered ethanol monosolvates
'International Union of Crystallography (IUCr)', 2020Co-Authors: Harish Chinthal Chayanna, Yathirajan H. S., Kadambar, Anish Kumar, Kalluraya Balakrishna, Foro Sabine, Glidewell ChristopherAbstract:AKK thanks the Department of Science and Technology, Government of India, for providing a Senior Research Fellowship under the DST–INSPIRE Scheme. HSY thanks the University Grants Commission, New Delhi, for the award of a BSR Faculty Fellowship for three years.Two new N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides have been prepared by acid-promoted condensation reactions between 3-aryl-4-formylsydnones and N-[(4-amino-5-sulfanylidene-1H-1,2,4-triazol-3-yl)methyl]benzamide, and both have been crystallized as ethanol monosolvates. N-{[4-(3-Phenyl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamide ethanol monosolvate, C19H15N7O3S·C2H6O ( I ), and N-({4-[3-(4-methylphenyl)-4-sydnonylideneamino]-5-sulfanylidene-1H-1,2,4-triazol-3-yl}methyl)benzamide ethanol monosolvate, C20H17N7O3S·C2H6O ( II ), differ only in the presence of a methyl group for ( II ) instead of a hydrogen atom for ( I ), and in both of them the ethanol component is disordered over two sets of atomic sites having occupancies of 0.836 (6) and 0.164 (6) in ( I ), and 0.906 (6) and 0.094 (6) in ( II ). Combinations of O—H⋯O and N—H⋯O hydrogen bonds link the molecules into cyclic, centrosymmetric four-molecule aggregates. Comparisons are made with the structures of some related compounds.Publisher PDFPeer reviewe
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Four closely related N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)Benzamides: order versus disorder, and similar molecular conformations but different modes of supramolecular aggregation, with a new disordered refinement of 2-amino-3-ben
'International Union of Crystallography (IUCr)', 2018Co-Authors: Sagar B. K., Yathirajan H. S., Rathore, Ravindranath S., Glidewell ChristopherAbstract:Four closely related N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)Benzamides, bearing different substituents on the benzamide ring, have been synthesized and structurally characterized. In each of N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-3-fluorobenzamide, C22H18FNO2S, (I), N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-4-chlorobenzamide, C22H18ClNO2S, (II), N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-2,6-difluorobenzamide, C22H17F2NO2S, (III), and N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-2-methoxybenzamide, C23H21NO3S, (IV), the last of which crystallizes with Z′ = 2 in the space group P[\overline{1}], the fused six-membered ring adopts a half-chair conformation. In each of (I)–(III), this ring is disordered over two sets of atomic sites having occupancies of 0.811 (6) and 0.189 (6) in (I), 0.645 (7) and 0.355 (7) in (II), and 0.784 (6) and 0.216 (6) in (III), such that the two disorder components of the ring are almost enantiomeric. Molecules of (I) are linked into chains by π–π stacking interactions, and those of (II) are linked into chains by a C—H⋯π hydrogen bond. A combination of two C—H⋯O hydrogen bonds and two C—H⋯π hydrogen bonds links the molecules of (III) into complex sheets, but the molecules of (IV) are linked by a combination of two hydrogen bonds, one each of the C—H⋯O and C—H⋯π types, to form centrosymmetric tetramers. The structures of (I)–(IV) are compared with that of the unsubstituted analogue N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzamide and a new refinement of the parent amine 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophene, using the original data set, has found that here too the fused six-membered ring exhibits conformational disorder, with occupancies of 0.887 (9) and 0.113 (9). Comparisons are made with some related compounds
Guillermo Senisterra - One of the best experts on this subject based on the ideXlab platform.
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Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1).
Journal of medicinal chemistry, 2016Co-Authors: Matthaeus Getlik, Aiping Dong, David Smil, Yuri Bolshan, Ekaterina Kuznetsova, Carlos Armando Zepeda-velazquez, Gennady Poda, Richard Marcellus, Guillermo SenisterraAbstract:WD repeat-containing protein 5 (WDR5) is an important component of the multiprotein complex essential for activating mixed-lineage leukemia 1 (MLL1). Rearrangement of the MLL1 gene is associated with onset and progression of acute myeloid and lymphoblastic leukemias, and targeting the WDR5-MLL1 interaction may result in new cancer therapeutics. Our previous work showed that binding of small molecule ligands to WDR5 can modulate its interaction with MLL1, suppressing MLL1 methyltransferase activity. Initial structure-activity relationship studies identified N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) Benzamides as potent and selective antagonists of this protein-protein interaction. Guided by crystal structure data and supported by in silico library design, we optimized the scaffold by varying the C-1 benzamide and C-5 substituents. This allowed us to develop the first highly potent (Kdisp < 100 nM) small molecule antagonists of the WDR5-MLL1 interaction and demonstrate that N-(4-(4-methylpiperazin-1-yl)-3'-(morpholinomethyl)-[1,1'-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide 16d (OICR-9429) is a potent and selective chemical probe suitable to help dissect the biological role of WDR5.
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structure based optimization of a small molecule antagonist of the interaction between wd repeat containing protein 5 wdr5 and mixed lineage leukemia 1 mll1
Journal of Medicinal Chemistry, 2016Co-Authors: Matthaeus Getlik, Aiping Dong, David Smil, Yuri Bolshan, Ekaterina Kuznetsova, Gennady Poda, Richard Marcellus, Carlos Zepedavelazquez, Guillermo SenisterraAbstract:WD repeat-containing protein 5 (WDR5) is an important component of the multiprotein complex essential for activating mixed-lineage leukemia 1 (MLL1). Rearrangement of the MLL1 gene is associated with onset and progression of acute myeloid and lymphoblastic leukemias, and targeting the WDR5-MLL1 interaction may result in new cancer therapeutics. Our previous work showed that binding of small molecule ligands to WDR5 can modulate its interaction with MLL1, suppressing MLL1 methyltransferase activity. Initial structure–activity relationship studies identified N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) Benzamides as potent and selective antagonists of this protein–protein interaction. Guided by crystal structure data and supported by in silico library design, we optimized the scaffold by varying the C-1 benzamide and C-5 substituents. This allowed us to develop the first highly potent (Kdisp < 100 nM) small molecule antagonists of the WDR5-MLL1 interaction and demonstrate that N-(4-(4-methylpiperazin...
Harish Chinthal Chayanna - One of the best experts on this subject based on the ideXlab platform.
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Two N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides as disordered ethanol monosolvates
'International Union of Crystallography (IUCr)', 2020Co-Authors: Harish Chinthal Chayanna, Yathirajan H. S., Kadambar, Anish Kumar, Kalluraya Balakrishna, Foro Sabine, Glidewell ChristopherAbstract:Two new N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides have been prepared by acid-promoted condensation reactions between 3-aryl-4-formylsydnones and N-[(4-amino-5-sulfanylidene-1H-1,2,4-triazol-3-yl)methyl]benzamide, and both have been crystallized as ethanol monosolvates. N-{[4-(3-Phenyl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamide ethanol monosolvate, C19H15N7O3S·C2H6O (I), and N-({4-[3-(4-methylphenyl)-4-sydnonylideneamino]-5-sulfanylidene-1H-1,2,4-triazol-3-yl}methyl)benzamide ethanol monosolvate, C20H17N7O3S·C2H6O (II), differ only in the presence of a methyl group for (II) instead of a hydrogen atom for (I), and in both of them the ethanol component is disordered over two sets of atomic sites having occupancies of 0.836 (6) and 0.164 (6) in (I), and 0.906 (6) and 0.094 (6) in (II). Combinations of O—H⋯O and N—H⋯O hydrogen bonds link the molecules into cyclic, centrosymmetric four-molecule aggregates. Comparisons are made with the structures of some related compounds
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Two N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides as disordered ethanol monosolvates
'International Union of Crystallography (IUCr)', 2020Co-Authors: Harish Chinthal Chayanna, Yathirajan H. S., Kadambar, Anish Kumar, Kalluraya Balakrishna, Foro Sabine, Glidewell ChristopherAbstract:AKK thanks the Department of Science and Technology, Government of India, for providing a Senior Research Fellowship under the DST–INSPIRE Scheme. HSY thanks the University Grants Commission, New Delhi, for the award of a BSR Faculty Fellowship for three years.Two new N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides have been prepared by acid-promoted condensation reactions between 3-aryl-4-formylsydnones and N-[(4-amino-5-sulfanylidene-1H-1,2,4-triazol-3-yl)methyl]benzamide, and both have been crystallized as ethanol monosolvates. N-{[4-(3-Phenyl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamide ethanol monosolvate, C19H15N7O3S·C2H6O ( I ), and N-({4-[3-(4-methylphenyl)-4-sydnonylideneamino]-5-sulfanylidene-1H-1,2,4-triazol-3-yl}methyl)benzamide ethanol monosolvate, C20H17N7O3S·C2H6O ( II ), differ only in the presence of a methyl group for ( II ) instead of a hydrogen atom for ( I ), and in both of them the ethanol component is disordered over two sets of atomic sites having occupancies of 0.836 (6) and 0.164 (6) in ( I ), and 0.906 (6) and 0.094 (6) in ( II ). Combinations of O—H⋯O and N—H⋯O hydrogen bonds link the molecules into cyclic, centrosymmetric four-molecule aggregates. Comparisons are made with the structures of some related compounds.Publisher PDFPeer reviewe
Gennady Poda - One of the best experts on this subject based on the ideXlab platform.
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Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1).
Journal of medicinal chemistry, 2016Co-Authors: Matthaeus Getlik, Aiping Dong, David Smil, Yuri Bolshan, Ekaterina Kuznetsova, Carlos Armando Zepeda-velazquez, Gennady Poda, Richard Marcellus, Guillermo SenisterraAbstract:WD repeat-containing protein 5 (WDR5) is an important component of the multiprotein complex essential for activating mixed-lineage leukemia 1 (MLL1). Rearrangement of the MLL1 gene is associated with onset and progression of acute myeloid and lymphoblastic leukemias, and targeting the WDR5-MLL1 interaction may result in new cancer therapeutics. Our previous work showed that binding of small molecule ligands to WDR5 can modulate its interaction with MLL1, suppressing MLL1 methyltransferase activity. Initial structure-activity relationship studies identified N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) Benzamides as potent and selective antagonists of this protein-protein interaction. Guided by crystal structure data and supported by in silico library design, we optimized the scaffold by varying the C-1 benzamide and C-5 substituents. This allowed us to develop the first highly potent (Kdisp < 100 nM) small molecule antagonists of the WDR5-MLL1 interaction and demonstrate that N-(4-(4-methylpiperazin-1-yl)-3'-(morpholinomethyl)-[1,1'-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide 16d (OICR-9429) is a potent and selective chemical probe suitable to help dissect the biological role of WDR5.
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structure based optimization of a small molecule antagonist of the interaction between wd repeat containing protein 5 wdr5 and mixed lineage leukemia 1 mll1
Journal of Medicinal Chemistry, 2016Co-Authors: Matthaeus Getlik, Aiping Dong, David Smil, Yuri Bolshan, Ekaterina Kuznetsova, Gennady Poda, Richard Marcellus, Carlos Zepedavelazquez, Guillermo SenisterraAbstract:WD repeat-containing protein 5 (WDR5) is an important component of the multiprotein complex essential for activating mixed-lineage leukemia 1 (MLL1). Rearrangement of the MLL1 gene is associated with onset and progression of acute myeloid and lymphoblastic leukemias, and targeting the WDR5-MLL1 interaction may result in new cancer therapeutics. Our previous work showed that binding of small molecule ligands to WDR5 can modulate its interaction with MLL1, suppressing MLL1 methyltransferase activity. Initial structure–activity relationship studies identified N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) Benzamides as potent and selective antagonists of this protein–protein interaction. Guided by crystal structure data and supported by in silico library design, we optimized the scaffold by varying the C-1 benzamide and C-5 substituents. This allowed us to develop the first highly potent (Kdisp < 100 nM) small molecule antagonists of the WDR5-MLL1 interaction and demonstrate that N-(4-(4-methylpiperazin...
Yathirajan H. S. - One of the best experts on this subject based on the ideXlab platform.
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Two N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides as disordered ethanol monosolvates
'International Union of Crystallography (IUCr)', 2020Co-Authors: Harish Chinthal Chayanna, Yathirajan H. S., Kadambar, Anish Kumar, Kalluraya Balakrishna, Foro Sabine, Glidewell ChristopherAbstract:Two new N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides have been prepared by acid-promoted condensation reactions between 3-aryl-4-formylsydnones and N-[(4-amino-5-sulfanylidene-1H-1,2,4-triazol-3-yl)methyl]benzamide, and both have been crystallized as ethanol monosolvates. N-{[4-(3-Phenyl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamide ethanol monosolvate, C19H15N7O3S·C2H6O (I), and N-({4-[3-(4-methylphenyl)-4-sydnonylideneamino]-5-sulfanylidene-1H-1,2,4-triazol-3-yl}methyl)benzamide ethanol monosolvate, C20H17N7O3S·C2H6O (II), differ only in the presence of a methyl group for (II) instead of a hydrogen atom for (I), and in both of them the ethanol component is disordered over two sets of atomic sites having occupancies of 0.836 (6) and 0.164 (6) in (I), and 0.906 (6) and 0.094 (6) in (II). Combinations of O—H⋯O and N—H⋯O hydrogen bonds link the molecules into cyclic, centrosymmetric four-molecule aggregates. Comparisons are made with the structures of some related compounds
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Two N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides as disordered ethanol monosolvates
'International Union of Crystallography (IUCr)', 2020Co-Authors: Harish Chinthal Chayanna, Yathirajan H. S., Kadambar, Anish Kumar, Kalluraya Balakrishna, Foro Sabine, Glidewell ChristopherAbstract:AKK thanks the Department of Science and Technology, Government of India, for providing a Senior Research Fellowship under the DST–INSPIRE Scheme. HSY thanks the University Grants Commission, New Delhi, for the award of a BSR Faculty Fellowship for three years.Two new N-{[4-(3-aryl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}Benzamides have been prepared by acid-promoted condensation reactions between 3-aryl-4-formylsydnones and N-[(4-amino-5-sulfanylidene-1H-1,2,4-triazol-3-yl)methyl]benzamide, and both have been crystallized as ethanol monosolvates. N-{[4-(3-Phenyl-4-sydnonylideneamino)-5-sulfanylidene-1H-1,2,4-triazol-3-yl]methyl}benzamide ethanol monosolvate, C19H15N7O3S·C2H6O ( I ), and N-({4-[3-(4-methylphenyl)-4-sydnonylideneamino]-5-sulfanylidene-1H-1,2,4-triazol-3-yl}methyl)benzamide ethanol monosolvate, C20H17N7O3S·C2H6O ( II ), differ only in the presence of a methyl group for ( II ) instead of a hydrogen atom for ( I ), and in both of them the ethanol component is disordered over two sets of atomic sites having occupancies of 0.836 (6) and 0.164 (6) in ( I ), and 0.906 (6) and 0.094 (6) in ( II ). Combinations of O—H⋯O and N—H⋯O hydrogen bonds link the molecules into cyclic, centrosymmetric four-molecule aggregates. Comparisons are made with the structures of some related compounds.Publisher PDFPeer reviewe
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Four closely related N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)Benzamides: order versus disorder, and similar molecular conformations but different modes of supramolecular aggregation, with a new disordered refinement of 2-amino-3-ben
'International Union of Crystallography (IUCr)', 2018Co-Authors: Sagar B. K., Yathirajan H. S., Rathore, Ravindranath S., Glidewell ChristopherAbstract:Four closely related N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)Benzamides, bearing different substituents on the benzamide ring, have been synthesized and structurally characterized. In each of N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-3-fluorobenzamide, C22H18FNO2S, (I), N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-4-chlorobenzamide, C22H18ClNO2S, (II), N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-2,6-difluorobenzamide, C22H17F2NO2S, (III), and N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-2-methoxybenzamide, C23H21NO3S, (IV), the last of which crystallizes with Z′ = 2 in the space group P[\overline{1}], the fused six-membered ring adopts a half-chair conformation. In each of (I)–(III), this ring is disordered over two sets of atomic sites having occupancies of 0.811 (6) and 0.189 (6) in (I), 0.645 (7) and 0.355 (7) in (II), and 0.784 (6) and 0.216 (6) in (III), such that the two disorder components of the ring are almost enantiomeric. Molecules of (I) are linked into chains by π–π stacking interactions, and those of (II) are linked into chains by a C—H⋯π hydrogen bond. A combination of two C—H⋯O hydrogen bonds and two C—H⋯π hydrogen bonds links the molecules of (III) into complex sheets, but the molecules of (IV) are linked by a combination of two hydrogen bonds, one each of the C—H⋯O and C—H⋯π types, to form centrosymmetric tetramers. The structures of (I)–(IV) are compared with that of the unsubstituted analogue N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzamide and a new refinement of the parent amine 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophene, using the original data set, has found that here too the fused six-membered ring exhibits conformational disorder, with occupancies of 0.887 (9) and 0.113 (9). Comparisons are made with some related compounds