The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
John Drewe - One of the best experts on this subject based on the ideXlab platform.
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discovery of substituted 4 anilino 2 arylpyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay 2 structure activity relationships of the 2 aryl group
Bioorganic & Medicinal Chemistry Letters, 2009Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Candace Crogangrundy, Shailaja Kasibhatla, Ben Tseng, John Drewe, Sui Xiong CaiAbstract:Abstract As a continuation of our efforts to discover and develop the apoptosis inducing 4-anilino-2-(2-pyridyl)pyrimidines as potential anticancer agents, we explored replacing the 2-pyridyl group by other aryl groups. SAR studies showed that the 2-pyridyl group can be replaced by a 3-pyridyl, 4-pyridyl and 2-pyrazinyl group, and that the SAR for the anilino group was similar to that of the 2-pyridyl series. However, replacement of the 2-pyridyl group by a phenyl group, a 3,5-dichloro-4-pyridyl group, or a saturated ring led to inactive compounds. Several potent compounds, including 2f, 3d, 3j and 4a, with EC50 values of 0.048–0.024 μM in the apoptosis induction Assay against T47D cells, were identified through the SAR studies. In a Tubulin Polymerization Assay, compound 2f, which was active against all the three cell lines tested (T47D, HTC116 and SNU398), inhibited Tubulin Polymerization with an IC50 value of 0.5 μM, while compound 2a, which was active against T47D cells but not active against HTC116 and SNU398 cells, was not active in the Tubulin Assay at up to 50 μM.
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discovery of substituted 4 anilino 2 2 pyridyl pyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay part 1 structure activity relationships of the 4 anilino group
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Shailaja Kasibhatla, Ben Tseng, Yang Wang, Gisela Claassen, John DreweAbstract:Abstract A series of 4-anilino-2-(2-pyridyl)pyrimidines has been discovered as a new class of potent inducers of apoptosis using a cell-based HTS Assay. Compound 5a was found to arrest T47D cells in G 2 /M and induced apoptosis. SAR studies showed that a small and electron-donating group at the meta -position of the anilino ring is important for activity. A 20-fold increase in potency, from hit compound 4-(3-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine ( 5a ) to lead compound 4-(2,5-dimethoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine ( 5l ), was obtained through the SAR studies. Compound 5l is highly active with an EC 50 value of 18 nM in the caspase activation Assay in T47D breast cells. Interestingly, 5a and other meta -mono-substituted compounds were active against T47D cells but were not active against H1299 and HT29 cells, while 5l and other 2,5-disubstituted compounds were active against all the three cells. In a Tubulin Polymerization Assay, compound 5l inhibited Tubulin Polymerization with an IC 50 value of 5a was not active up to 50 μM.
Nilantha Sudath Sirisoma - One of the best experts on this subject based on the ideXlab platform.
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discovery of substituted 4 anilino 2 arylpyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay 2 structure activity relationships of the 2 aryl group
Bioorganic & Medicinal Chemistry Letters, 2009Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Candace Crogangrundy, Shailaja Kasibhatla, Ben Tseng, John Drewe, Sui Xiong CaiAbstract:Abstract As a continuation of our efforts to discover and develop the apoptosis inducing 4-anilino-2-(2-pyridyl)pyrimidines as potential anticancer agents, we explored replacing the 2-pyridyl group by other aryl groups. SAR studies showed that the 2-pyridyl group can be replaced by a 3-pyridyl, 4-pyridyl and 2-pyrazinyl group, and that the SAR for the anilino group was similar to that of the 2-pyridyl series. However, replacement of the 2-pyridyl group by a phenyl group, a 3,5-dichloro-4-pyridyl group, or a saturated ring led to inactive compounds. Several potent compounds, including 2f, 3d, 3j and 4a, with EC50 values of 0.048–0.024 μM in the apoptosis induction Assay against T47D cells, were identified through the SAR studies. In a Tubulin Polymerization Assay, compound 2f, which was active against all the three cell lines tested (T47D, HTC116 and SNU398), inhibited Tubulin Polymerization with an IC50 value of 0.5 μM, while compound 2a, which was active against T47D cells but not active against HTC116 and SNU398 cells, was not active in the Tubulin Assay at up to 50 μM.
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discovery of substituted 4 anilino 2 2 pyridyl pyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay part 1 structure activity relationships of the 4 anilino group
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Shailaja Kasibhatla, Ben Tseng, Yang Wang, Gisela Claassen, John DreweAbstract:Abstract A series of 4-anilino-2-(2-pyridyl)pyrimidines has been discovered as a new class of potent inducers of apoptosis using a cell-based HTS Assay. Compound 5a was found to arrest T47D cells in G 2 /M and induced apoptosis. SAR studies showed that a small and electron-donating group at the meta -position of the anilino ring is important for activity. A 20-fold increase in potency, from hit compound 4-(3-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine ( 5a ) to lead compound 4-(2,5-dimethoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine ( 5l ), was obtained through the SAR studies. Compound 5l is highly active with an EC 50 value of 18 nM in the caspase activation Assay in T47D breast cells. Interestingly, 5a and other meta -mono-substituted compounds were active against T47D cells but were not active against H1299 and HT29 cells, while 5l and other 2,5-disubstituted compounds were active against all the three cells. In a Tubulin Polymerization Assay, compound 5l inhibited Tubulin Polymerization with an IC 50 value of 5a was not active up to 50 μM.
Sui Xiong Cai - One of the best experts on this subject based on the ideXlab platform.
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discovery of substituted 4 anilino 2 arylpyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay 2 structure activity relationships of the 2 aryl group
Bioorganic & Medicinal Chemistry Letters, 2009Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Candace Crogangrundy, Shailaja Kasibhatla, Ben Tseng, John Drewe, Sui Xiong CaiAbstract:Abstract As a continuation of our efforts to discover and develop the apoptosis inducing 4-anilino-2-(2-pyridyl)pyrimidines as potential anticancer agents, we explored replacing the 2-pyridyl group by other aryl groups. SAR studies showed that the 2-pyridyl group can be replaced by a 3-pyridyl, 4-pyridyl and 2-pyrazinyl group, and that the SAR for the anilino group was similar to that of the 2-pyridyl series. However, replacement of the 2-pyridyl group by a phenyl group, a 3,5-dichloro-4-pyridyl group, or a saturated ring led to inactive compounds. Several potent compounds, including 2f, 3d, 3j and 4a, with EC50 values of 0.048–0.024 μM in the apoptosis induction Assay against T47D cells, were identified through the SAR studies. In a Tubulin Polymerization Assay, compound 2f, which was active against all the three cell lines tested (T47D, HTC116 and SNU398), inhibited Tubulin Polymerization with an IC50 value of 0.5 μM, while compound 2a, which was active against T47D cells but not active against HTC116 and SNU398 cells, was not active in the Tubulin Assay at up to 50 μM.
Ben Tseng - One of the best experts on this subject based on the ideXlab platform.
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discovery of substituted 4 anilino 2 arylpyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay 2 structure activity relationships of the 2 aryl group
Bioorganic & Medicinal Chemistry Letters, 2009Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Candace Crogangrundy, Shailaja Kasibhatla, Ben Tseng, John Drewe, Sui Xiong CaiAbstract:Abstract As a continuation of our efforts to discover and develop the apoptosis inducing 4-anilino-2-(2-pyridyl)pyrimidines as potential anticancer agents, we explored replacing the 2-pyridyl group by other aryl groups. SAR studies showed that the 2-pyridyl group can be replaced by a 3-pyridyl, 4-pyridyl and 2-pyrazinyl group, and that the SAR for the anilino group was similar to that of the 2-pyridyl series. However, replacement of the 2-pyridyl group by a phenyl group, a 3,5-dichloro-4-pyridyl group, or a saturated ring led to inactive compounds. Several potent compounds, including 2f, 3d, 3j and 4a, with EC50 values of 0.048–0.024 μM in the apoptosis induction Assay against T47D cells, were identified through the SAR studies. In a Tubulin Polymerization Assay, compound 2f, which was active against all the three cell lines tested (T47D, HTC116 and SNU398), inhibited Tubulin Polymerization with an IC50 value of 0.5 μM, while compound 2a, which was active against T47D cells but not active against HTC116 and SNU398 cells, was not active in the Tubulin Assay at up to 50 μM.
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discovery of substituted 4 anilino 2 2 pyridyl pyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay part 1 structure activity relationships of the 4 anilino group
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Shailaja Kasibhatla, Ben Tseng, Yang Wang, Gisela Claassen, John DreweAbstract:Abstract A series of 4-anilino-2-(2-pyridyl)pyrimidines has been discovered as a new class of potent inducers of apoptosis using a cell-based HTS Assay. Compound 5a was found to arrest T47D cells in G 2 /M and induced apoptosis. SAR studies showed that a small and electron-donating group at the meta -position of the anilino ring is important for activity. A 20-fold increase in potency, from hit compound 4-(3-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine ( 5a ) to lead compound 4-(2,5-dimethoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine ( 5l ), was obtained through the SAR studies. Compound 5l is highly active with an EC 50 value of 18 nM in the caspase activation Assay in T47D breast cells. Interestingly, 5a and other meta -mono-substituted compounds were active against T47D cells but were not active against H1299 and HT29 cells, while 5l and other 2,5-disubstituted compounds were active against all the three cells. In a Tubulin Polymerization Assay, compound 5l inhibited Tubulin Polymerization with an IC 50 value of 5a was not active up to 50 μM.
Azra Pervin - One of the best experts on this subject based on the ideXlab platform.
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discovery of substituted 4 anilino 2 arylpyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay 2 structure activity relationships of the 2 aryl group
Bioorganic & Medicinal Chemistry Letters, 2009Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Candace Crogangrundy, Shailaja Kasibhatla, Ben Tseng, John Drewe, Sui Xiong CaiAbstract:Abstract As a continuation of our efforts to discover and develop the apoptosis inducing 4-anilino-2-(2-pyridyl)pyrimidines as potential anticancer agents, we explored replacing the 2-pyridyl group by other aryl groups. SAR studies showed that the 2-pyridyl group can be replaced by a 3-pyridyl, 4-pyridyl and 2-pyrazinyl group, and that the SAR for the anilino group was similar to that of the 2-pyridyl series. However, replacement of the 2-pyridyl group by a phenyl group, a 3,5-dichloro-4-pyridyl group, or a saturated ring led to inactive compounds. Several potent compounds, including 2f, 3d, 3j and 4a, with EC50 values of 0.048–0.024 μM in the apoptosis induction Assay against T47D cells, were identified through the SAR studies. In a Tubulin Polymerization Assay, compound 2f, which was active against all the three cell lines tested (T47D, HTC116 and SNU398), inhibited Tubulin Polymerization with an IC50 value of 0.5 μM, while compound 2a, which was active against T47D cells but not active against HTC116 and SNU398 cells, was not active in the Tubulin Assay at up to 50 μM.
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discovery of substituted 4 anilino 2 2 pyridyl pyrimidines as a new series of apoptosis inducers using a cell and caspase based high throughput screening Assay part 1 structure activity relationships of the 4 anilino group
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Nilantha Sudath Sirisoma, Azra Pervin, Bao Nguyen, Shailaja Kasibhatla, Ben Tseng, Yang Wang, Gisela Claassen, John DreweAbstract:Abstract A series of 4-anilino-2-(2-pyridyl)pyrimidines has been discovered as a new class of potent inducers of apoptosis using a cell-based HTS Assay. Compound 5a was found to arrest T47D cells in G 2 /M and induced apoptosis. SAR studies showed that a small and electron-donating group at the meta -position of the anilino ring is important for activity. A 20-fold increase in potency, from hit compound 4-(3-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine ( 5a ) to lead compound 4-(2,5-dimethoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine ( 5l ), was obtained through the SAR studies. Compound 5l is highly active with an EC 50 value of 18 nM in the caspase activation Assay in T47D breast cells. Interestingly, 5a and other meta -mono-substituted compounds were active against T47D cells but were not active against H1299 and HT29 cells, while 5l and other 2,5-disubstituted compounds were active against all the three cells. In a Tubulin Polymerization Assay, compound 5l inhibited Tubulin Polymerization with an IC 50 value of 5a was not active up to 50 μM.
