Tag: 324.3737

Predicting the potency of hERG K⁺ channel inhibition by combining 3D-QSAR pharmacophore and 2D-QSAR models was written by Tan, Yayu;Chen, Yadong;You, Qidong;Sun, Haopeng;Li, Manhua. And the article was included in Journal of Molecular Modeling in 2012.Product Details of 115956-12-2 This article mentions the following:

Blockade of the hERG K⁺ channel has been identified as the most important mechanism of QT interval prolongation and thus inducing cardiac risk. In this work, an ensemble of 3D-QSAR pharmacophore models was constructed to provide insight into the determinants of the interactions between the hERG K⁺ channel and channel inhibitors. To predict hERG inhibitory activities, the predicted values from the ensemble of models were averaged, and the results thus obtained showed that the predictive ability of the combined 3D-QSAR pharmacophore model was greater that those of the individual models. Also, using the same training and test sets, a 2D-QSAR model based on a heuristic machine-learning method was developed in order to analyze the physicochem. characters of hERG inhibitors. The models indicated that the inhibitors have certain key inhibitory features in common, including hydrophobicity, aromaticity, and flexibility. A final model was developed by combining the combined 3D-QSAR pharmacophore with the 2D-QSAR model, and this final model outperformed any other individual model, showing the highest predictive ability and the lowest deviation. This model can not only predict hERG inhibitory potency accurately, thus allowing fast cardiac safety evaluation, but it provides an effective tool for avoiding hERG inhibitory liability and thus enhanced cardiac risk in the design and optimization of new chem. entities. In the experiment, the researchers used many compounds, for example, rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2Product Details of 115956-12-2).

rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Product Details of 115956-12-2

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Effect of selection of QTc formula on eligibility of cancer patients for phase I clinical trials was written by Borad, Mitesh J.;Soman, Arundhati D.;Benjamin, Martin;Casa, Daniel;Tembe, Waibhav D.;Piper, Barbara F.;Ramanathan, Ramesh;Tibes, Raoul;Jameson, Gayle;Ansaldo, Karen;Hoff, Daniel D.. And the article was included in Investigational New Drugs in 2013.Computed Properties of C19H20N2O3 This article mentions the following:

A retrospective anal. of 130 patients was conducted in a Phase I oncol. clinic to assess the effect of QTc formula selection on clin. trial eligibility. QTc values were calculated from screening electrocardiograms using 7 formulas (Bazett, Fridericia, Framingham, Hodges, Mayeda, Van de Water and Wohlfart). QTc values>470 ms for females and>450 ms for males were used to define prolongation. Concomitant medication potential for QTc prolongation was determined using a public database (AzCert). Ineligibility rates ranged from 3.1 % to 17.7 % (Framingham: 3.1 %, Van de Water: 3.1 %, Hodges: 3.1 %, Wohlfart: 3.1 %, Fridericia: 3.9 %, Bazett: 10.8 % and Mayeda: 17.7 %). A consistent ineligibility rate was achieved by using formulas-specific thresholds. Fifty one percent of patients were taking concomitant medications with QTc prolongation potential. The proportion of concomitant medications with the potential to prolong QTc was 11.57 % (96 of 830). Uniform criteria and guidelines for selection of QTc formulas need to be developed. Formulas-specific QTc thresholds also need to be specified. In the experiment, the researchers used many compounds, for example, rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2Computed Properties of C19H20N2O3).

rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2) belongs to indole derivatives. In addition to tryptophan, indigo, and indoleacetic acid, numerous compounds obtainable from plant or animal sources contain the indole molecular structure. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Computed Properties of C19H20N2O3

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Current Use of Domperidone and Co-prescribing of Medications that Increase Its Arrhythmogenic Potential Among Older Adults: A Population-Based Cohort Study in Ontario, Canada was written by Rojas-Fernandez, Carlos;Stephenson, Anne L.;Fischer, Hadas D.;Wang, Xuesong;Mestre, Tiago;Hutson, Janine R.;Pondal, Margarita;Lee, Douglas S.;Rochon, Paula A.;Marras, Connie. And the article was included in Drugs & Aging in 2014.Synthetic Route of C19H20N2O3 This article mentions the following:

Background and Objectives: Domperidone is commonly used to treat nausea and gastrointestinal disorders. Recent data suggests that it may increase the risk of sudden cardiac death, particularly in older people. Little is known about how it is used in contemporary practice. This study sought to characterize the population of older adults newly dispensed domperidone, describe dosages of domperidone used, and determine the frequency of co-prescribing domperidone with medications that may increase the arrhythmogenic potential of domperidone. Methods: This is a retrospective cohort study using administrative health database information from Ontario, Canada. Prescription medication records were obtained from the Ontario Drug Benefit Claims Database. Diagnostic codes were obtained from the Ontario Health Insurance Plan Database, the Canadian Institute for Health Information Discharge Abstract Database, and the same-day surgery database. Patients who received a new prescription for domperidone between Apr. 1, 2003 and March 31, 2010 were included. Results: A total of 122,233 patients met inclusion criteria; 85 % were between 66 and 84 years old and 63 % were female. The mean estimated daily domperidone dose was 35 mg, and the estimated daily dose was <40 mg for 62 % of users. Strong or moderately strong cytochrome P 450 (CYP) 3A4 inhibitors were co-prescribed for 4.3 and 10.7 % of users, while medications with a known risk or possible risk for torsades de pointes (TdP) were co-prescribed to 18.3 and 18.8 % of users. Conclusions: Older domperidone users were commonly co-prescribed drugs with the potential to increase the risk for TdP. These combinations should be avoided, as iatrogenic QT prolongation is a modifiable risk factor for TdP. In the experiment, the researchers used many compounds, for example, rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2Synthetic Route of C19H20N2O3).

rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). Synthetic Route of C19H20N2O3

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Effect of selection of QTc formula on eligibility of cancer patients for phase I clinical trials was written by Borad, Mitesh J.;Soman, Arundhati D.;Benjamin, Martin;Casa, Daniel;Tembe, Waibhav D.;Piper, Barbara F.;Ramanathan, Ramesh;Tibes, Raoul;Jameson, Gayle;Ansaldo, Karen;Hoff, Daniel D.. And the article was included in Investigational New Drugs in 2013.Computed Properties of C19H20N2O3 This article mentions the following:

A retrospective anal. of 130 patients was conducted in a Phase I oncol. clinic to assess the effect of QTc formula selection on clin. trial eligibility. QTc values were calculated from screening electrocardiograms using 7 formulas (Bazett, Fridericia, Framingham, Hodges, Mayeda, Van de Water and Wohlfart). QTc values>470 ms for females and>450 ms for males were used to define prolongation. Concomitant medication potential for QTc prolongation was determined using a public database (AzCert). Ineligibility rates ranged from 3.1 % to 17.7 % (Framingham: 3.1 %, Van de Water: 3.1 %, Hodges: 3.1 %, Wohlfart: 3.1 %, Fridericia: 3.9 %, Bazett: 10.8 % and Mayeda: 17.7 %). A consistent ineligibility rate was achieved by using formulas-specific thresholds. Fifty one percent of patients were taking concomitant medications with QTc prolongation potential. The proportion of concomitant medications with the potential to prolong QTc was 11.57 % (96 of 830). Uniform criteria and guidelines for selection of QTc formulas need to be developed. Formulas-specific QTc thresholds also need to be specified. In the experiment, the researchers used many compounds, for example, rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2Computed Properties of C19H20N2O3).

rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2) belongs to indole derivatives. In addition to tryptophan, indigo, and indoleacetic acid, numerous compounds obtainable from plant or animal sources contain the indole molecular structure. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Computed Properties of C19H20N2O3

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Current Use of Domperidone and Co-prescribing of Medications that Increase Its Arrhythmogenic Potential Among Older Adults: A Population-Based Cohort Study in Ontario, Canada was written by Rojas-Fernandez, Carlos;Stephenson, Anne L.;Fischer, Hadas D.;Wang, Xuesong;Mestre, Tiago;Hutson, Janine R.;Pondal, Margarita;Lee, Douglas S.;Rochon, Paula A.;Marras, Connie. And the article was included in Drugs & Aging in 2014.Synthetic Route of C19H20N2O3 This article mentions the following:

Background and Objectives: Domperidone is commonly used to treat nausea and gastrointestinal disorders. Recent data suggests that it may increase the risk of sudden cardiac death, particularly in older people. Little is known about how it is used in contemporary practice. This study sought to characterize the population of older adults newly dispensed domperidone, describe dosages of domperidone used, and determine the frequency of co-prescribing domperidone with medications that may increase the arrhythmogenic potential of domperidone. Methods: This is a retrospective cohort study using administrative health database information from Ontario, Canada. Prescription medication records were obtained from the Ontario Drug Benefit Claims Database. Diagnostic codes were obtained from the Ontario Health Insurance Plan Database, the Canadian Institute for Health Information Discharge Abstract Database, and the same-day surgery database. Patients who received a new prescription for domperidone between Apr. 1, 2003 and March 31, 2010 were included. Results: A total of 122,233 patients met inclusion criteria; 85 % were between 66 and 84 years old and 63 % were female. The mean estimated daily domperidone dose was 35 mg, and the estimated daily dose was <40 mg for 62 % of users. Strong or moderately strong cytochrome P 450 (CYP) 3A4 inhibitors were co-prescribed for 4.3 and 10.7 % of users, while medications with a known risk or possible risk for torsades de pointes (TdP) were co-prescribed to 18.3 and 18.8 % of users. Conclusions: Older domperidone users were commonly co-prescribed drugs with the potential to increase the risk for TdP. These combinations should be avoided, as iatrogenic QT prolongation is a modifiable risk factor for TdP. In the experiment, the researchers used many compounds, for example, rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2Synthetic Route of C19H20N2O3).

rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). Synthetic Route of C19H20N2O3

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Predicting the potency of hERG K⁺ channel inhibition by combining 3D-QSAR pharmacophore and 2D-QSAR models was written by Tan, Yayu;Chen, Yadong;You, Qidong;Sun, Haopeng;Li, Manhua. And the article was included in Journal of Molecular Modeling in 2012.Product Details of 115956-12-2 This article mentions the following:

Blockade of the hERG K⁺ channel has been identified as the most important mechanism of QT interval prolongation and thus inducing cardiac risk. In this work, an ensemble of 3D-QSAR pharmacophore models was constructed to provide insight into the determinants of the interactions between the hERG K⁺ channel and channel inhibitors. To predict hERG inhibitory activities, the predicted values from the ensemble of models were averaged, and the results thus obtained showed that the predictive ability of the combined 3D-QSAR pharmacophore model was greater that those of the individual models. Also, using the same training and test sets, a 2D-QSAR model based on a heuristic machine-learning method was developed in order to analyze the physicochem. characters of hERG inhibitors. The models indicated that the inhibitors have certain key inhibitory features in common, including hydrophobicity, aromaticity, and flexibility. A final model was developed by combining the combined 3D-QSAR pharmacophore with the 2D-QSAR model, and this final model outperformed any other individual model, showing the highest predictive ability and the lowest deviation. This model can not only predict hERG inhibitory potency accurately, thus allowing fast cardiac safety evaluation, but it provides an effective tool for avoiding hERG inhibitory liability and thus enhanced cardiac risk in the design and optimization of new chem. entities. In the experiment, the researchers used many compounds, for example, rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2Product Details of 115956-12-2).

rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Product Details of 115956-12-2

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Current Use of Domperidone and Co-prescribing of Medications that Increase Its Arrhythmogenic Potential Among Older Adults: A Population-Based Cohort Study in Ontario, Canada was written by Rojas-Fernandez, Carlos;Stephenson, Anne L.;Fischer, Hadas D.;Wang, Xuesong;Mestre, Tiago;Hutson, Janine R.;Pondal, Margarita;Lee, Douglas S.;Rochon, Paula A.;Marras, Connie. And the article was included in Drugs & Aging in 2014.Synthetic Route of C19H20N2O3 This article mentions the following:

Background and Objectives: Domperidone is commonly used to treat nausea and gastrointestinal disorders. Recent data suggests that it may increase the risk of sudden cardiac death, particularly in older people. Little is known about how it is used in contemporary practice. This study sought to characterize the population of older adults newly dispensed domperidone, describe dosages of domperidone used, and determine the frequency of co-prescribing domperidone with medications that may increase the arrhythmogenic potential of domperidone. Methods: This is a retrospective cohort study using administrative health database information from Ontario, Canada. Prescription medication records were obtained from the Ontario Drug Benefit Claims Database. Diagnostic codes were obtained from the Ontario Health Insurance Plan Database, the Canadian Institute for Health Information Discharge Abstract Database, and the same-day surgery database. Patients who received a new prescription for domperidone between Apr. 1, 2003 and March 31, 2010 were included. Results: A total of 122,233 patients met inclusion criteria; 85 % were between 66 and 84 years old and 63 % were female. The mean estimated daily domperidone dose was 35 mg, and the estimated daily dose was <40 mg for 62 % of users. Strong or moderately strong cytochrome P 450 (CYP) 3A4 inhibitors were co-prescribed for 4.3 and 10.7 % of users, while medications with a known risk or possible risk for torsades de pointes (TdP) were co-prescribed to 18.3 and 18.8 % of users. Conclusions: Older domperidone users were commonly co-prescribed drugs with the potential to increase the risk for TdP. These combinations should be avoided, as iatrogenic QT prolongation is a modifiable risk factor for TdP. In the experiment, the researchers used many compounds, for example, rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2Synthetic Route of C19H20N2O3).

rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). Synthetic Route of C19H20N2O3

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Effect of selection of QTc formula on eligibility of cancer patients for phase I clinical trials was written by Borad, Mitesh J.;Soman, Arundhati D.;Benjamin, Martin;Casa, Daniel;Tembe, Waibhav D.;Piper, Barbara F.;Ramanathan, Ramesh;Tibes, Raoul;Jameson, Gayle;Ansaldo, Karen;Hoff, Daniel D.. And the article was included in Investigational New Drugs in 2013.Computed Properties of C19H20N2O3 This article mentions the following:

A retrospective anal. of 130 patients was conducted in a Phase I oncol. clinic to assess the effect of QTc formula selection on clin. trial eligibility. QTc values were calculated from screening electrocardiograms using 7 formulas (Bazett, Fridericia, Framingham, Hodges, Mayeda, Van de Water and Wohlfart). QTc values>470 ms for females and>450 ms for males were used to define prolongation. Concomitant medication potential for QTc prolongation was determined using a public database (AzCert). Ineligibility rates ranged from 3.1 % to 17.7 % (Framingham: 3.1 %, Van de Water: 3.1 %, Hodges: 3.1 %, Wohlfart: 3.1 %, Fridericia: 3.9 %, Bazett: 10.8 % and Mayeda: 17.7 %). A consistent ineligibility rate was achieved by using formulas-specific thresholds. Fifty one percent of patients were taking concomitant medications with QTc prolongation potential. The proportion of concomitant medications with the potential to prolong QTc was 11.57 % (96 of 830). Uniform criteria and guidelines for selection of QTc formulas need to be developed. Formulas-specific QTc thresholds also need to be specified. In the experiment, the researchers used many compounds, for example, rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2Computed Properties of C19H20N2O3).

rel-(5s,6R,8r,9aS)-3-Oxooctahydro-1H-2,6-methanoquinolizin-8-yl 1H-indole-3-carboxylate (cas: 115956-12-2) belongs to indole derivatives. In addition to tryptophan, indigo, and indoleacetic acid, numerous compounds obtainable from plant or animal sources contain the indole molecular structure. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Computed Properties of C19H20N2O3

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles