lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(Oc2ncc(Cl)c(C)c2Cl)ccc1-c1c(C)cnc(=O)n1C
InChIKey: CINBIPKMGSUMHJ-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 354 nM (pChEMBL 6.449999809265137)
Descriptors: MW 390.27, ALogP 4.87, HBA 5, HBD 0, PSA 57.01, QED 0.64
Compound (SMILES): Cc1cc(Oc2ncccc2C(F)(F)F)ccc1-c1c(C)cnc(=O)n1C
InChIKey: DYFZGOFCSNGJAB-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 337 nM (pChEMBL 6.46999979019165)
Descriptors: MW 375.35, ALogP 4.27, HBA 5, HBD 0, PSA 57.01, QED 0.69
Compound (SMILES): Cc1cc(Oc2nccc(C)c2Cl)ccc1-c1c(C)cnc(=O)n1C
InChIKey: SIGMOABZPODTJD-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 32.3 nM (pChEMBL 7.489999771118164)
Descriptors: MW 355.83, ALogP 4.21, HBA 5, HBD 0, PSA 57.01, QED 0.71
Compound (SMILES): Cc1cc(Oc2ncccc2C2CC2)ccc1-c1c(C)cnc(=O)n1C
InChIKey: CFVPUCGSRBYTQS-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 347.42, ALogP 4.13, HBA 5, HBD 0, PSA 57.01, QED 0.71
Compound (SMILES): Cc1cc(Oc2ncccc2Cl)ccc1-c1c(C)cnc(=O)n1C
InChIKey: UBNPQQHOEROCRV-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 349 nM (pChEMBL 6.460000038146973)
Descriptors: MW 341.8, ALogP 3.9, HBA 5, HBD 0, PSA 57.01, QED 0.72
Compound (SMILES): Cc1cc(Oc2ncccc2C(F)F)ccc1-c1c(C)c(=O)[nH]c(=O)n1C1CC1
InChIKey: IRQUYIIBOAXVDP-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 399.4, ALogP 4.28, HBA 5, HBD 1, PSA 76.98, QED 0.69
Compound (SMILES): Cc1cc(Oc2ncccc2C2CC2)ccc1-c1c(C)c(=O)[nH]c(=O)n1C
InChIKey: HKUMDHHNJIWXOV-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 15.3 nM (pChEMBL 7.820000171661377)
Descriptors: MW 363.42, ALogP 3.42, HBA 5, HBD 1, PSA 76.98, QED 0.77
Compound (SMILES): Cc1cc(Oc2ncc(F)cc2Cl)ccc1-c1c(C)c(=O)[nH]c(=O)n1C
InChIKey: SNBLYOJFYIQKDX-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 40.6 nM (pChEMBL 7.389999866485596)
Descriptors: MW 375.79, ALogP 3.34, HBA 5, HBD 1, PSA 76.98, QED 0.76
Compound (SMILES): CCn1c(-c2ccc(Oc3ncccc3Cl)cc2C)c(C)c(=O)[nH]c1=O
InChIKey: QNFMCVIETWMWIC-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 371.82, ALogP 3.68, HBA 5, HBD 1, PSA 76.98, QED 0.76
Compound (SMILES): CCc1c(-c2ccc(Oc3ncccc3Cl)cc2C)n(C)c(=O)[nH]c1=O
InChIKey: ZVBJFKGTUSVIFK-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 33.1 nM (pChEMBL 7.480000019073486)
Descriptors: MW 371.82, ALogP 3.45, HBA 5, HBD 1, PSA 76.98, QED 0.76
Compound (SMILES): Cc1cc(Oc2ncccc2C(F)(F)F)ccc1-c1c(C)c(=O)[nH]c(=O)n1C
InChIKey: AKQXQLUNFKDZBN-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 8.54 nM (pChEMBL 8.069999694824219)
Descriptors: MW 391.35, ALogP 3.56, HBA 5, HBD 1, PSA 76.98, QED 0.74
Compound (SMILES): Cc1cnc(Oc2ccc(-c3c(C)c(=O)[nH]c(=O)n3C)c(C)c2)c(Cl)c1
InChIKey: QDDZCKNTJUFORZ-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 371.82, ALogP 3.51, HBA 5, HBD 1, PSA 76.98, QED 0.76
Compound (SMILES): Cc1ccnc(Oc2ccc(-c3c(C)c(=O)[nH]c(=O)n3C)cc2)c1Cl
InChIKey: FQLCXVGWMXWHKT-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 10.9 nM (pChEMBL 7.960000038146973)
Descriptors: MW 357.8, ALogP 3.2, HBA 5, HBD 1, PSA 76.98, QED 0.78
Compound (SMILES): CCn1c(-c2ccc(Oc3ncccc3C(F)F)cc2C)c(C)c(=O)[nH]c1=O
InChIKey: AQJVLUHOWZSSPW-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 55.1 nM (pChEMBL 7.260000228881836)
Descriptors: MW 387.39, ALogP 3.97, HBA 5, HBD 1, PSA 76.98, QED 0.72
Compound (SMILES): Cc1cc(Oc2ncccc2C(F)F)ccc1-c1c(C)c(=O)[nH]c(=O)n1C
InChIKey: FLWPDFHBTSGXSA-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 17.5 nM (pChEMBL 7.760000228881836)
Descriptors: MW 373.36, ALogP 3.48, HBA 5, HBD 1, PSA 76.98, QED 0.76
Compound (SMILES): Cc1cc(Oc2ncccc2C(F)F)ccc1-c1c(C)n[nH]c(=O)c1C
InChIKey: TUWOXNPAAGERKH-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 44.3 nM (pChEMBL 7.349999904632568)
Descriptors: MW 357.36, ALogP 4.49, HBA 4, HBD 1, PSA 67.87, QED 0.75
Compound (SMILES): Cc1cc(Sc2ncccc2Cl)ccc1-c1c(C)c(=O)[nH]c(=O)n1C
InChIKey: UNRHEJKHGKMBNZ-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 35.7 nM (pChEMBL 7.449999809265137)
Descriptors: MW 373.87, ALogP 3.56, HBA 5, HBD 1, PSA 67.75, QED 0.76
Compound (SMILES): Cc1c(-c2ccc(Oc3ncccc3C(F)(F)F)c3[nH]ccc23)n(C)c(=O)[nH]c1=O
InChIKey: ZFJDLEQDDNOMPH-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Competition Binding Assay: The affinity of the compounds described herein was determined by competition binding assays similar to those described in Ryman-Rasmussen et al., Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists, Molecular Pharmacology 68(4):1039-1048 (2005). This radioligand binding assay used [3H]-SCH23390, a radiolabeled D1 ligand, to evaluate the ability of a test compound to compete with the radioligand when binding to a D1 receptor.D1 binding assays were performed using over-expressing LTK human cell lines. To determine basic assay parameters, ligand concentrations were determined from saturation binding studies where the Kd for [3H]-SCH23390 was found to be 1.3 nM. From tissue concentration curve studies, the optimal amount of tissue was determined to be 1.75 mg/mL per 96 well plate using 0.5 nM of [3H]-SCH23390. These ligand and tissue concentrations were used in time course studies to determine linearity and equilibrium.
Measurement: Ki = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 416.36, ALogP 3.74, HBA 5, HBD 2, PSA 92.77, QED 0.53
Compound (SMILES): Cc1nnc(C(C)C)n1C1CC2CCC(C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)c1ccc(NC(=O)COCC(N)=O)cc1
InChIKey: OMUNPLGAVFXFJF-OYGGZRDRSA-N
Target: C-C chemokine receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51681
Assay: Radioligand Binding Assay: Afterwards, the pharmacological profile of bivalent ligand 1 at the chemokine receptor CCR5 was characterized similarly. The competitive radioligand binding assay was conducted in CCR5 rhesus macaque membrane preparations from Chem-1 cells. Monovalent ligand 3 and compound 4, an analogue of maraviroc, were tested along under the same condition. Introduction of the 4-NH2 group onto the phenyl ring of maraviroc, as seen in compound 4, caused approximately 65-fold decrease in the binding affinity, compared to maraviroc. The decrease of the binding affinity was even more profound for bivalent ligand 1 and monovalent ligand 3, as their Ki values dropped to submicromolar range, respectively.
Measurement: Ki = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 643.78, ALogP 4.39, HBA 8, HBD 3, PSA 144.47, QED 0.29
Compound (SMILES): Cc1nnc(C(C)C)n1C1CC2CCC(C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)c1cccc(NC(=O)COCC(=O)NCCCCCCCNC(=O)COCC(=O)N[C@@H]2CC[C@@]3(O)[C@H]4Cc5ccc(O)c6c5[C@@]3(CCN4CC3CC3)[C@H]2O6)c1
InChIKey: UXTIQTCPQUYEFM-XJSRWQIGSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: A bivalent ligand 1 (FIG. 14) that combines the pharmacophores of naltrexone (a MOR antagonist) and maraviroc (a CCR5 antagonist) into one molecule was designed and synthesized. Herein is reported the characterization of this novel molecular probe in for its binding affinity, Ca2− flux functional activity, and HIV-1 inhibition potency. Bivalent ligand 1 was first characterized in hMOR-expressed CHO cells in the competitive radioligand binding assay as described previously.
Measurement: Ki = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 1197.48
Compound (SMILES): Cc1nnc(C(C)C)n1C1CC2CCC(C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)c1ccc(NC(=O)COC(C)(C)C)cc1
InChIKey: UMUYGAZDJCCJOO-IYCLCUOYSA-N
Target: C-C chemokine receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51681
Assay: Radioligand Binding Assay: Afterwards, the pharmacological profile of bivalent ligand 1 at the chemokine receptor CCR5 was characterized similarly. The competitive radioligand binding assay was conducted in CCR5 rhesus macaque membrane preparations from Chem-1 cells. Monovalent ligand 3 and compound 4, an analogue of maraviroc, were tested along under the same condition. Introduction of the 4-NH2 group onto the phenyl ring of maraviroc, as seen in compound 4, caused approximately 65-fold decrease in the binding affinity, compared to maraviroc. The decrease of the binding affinity was even more profound for bivalent ligand 1 and monovalent ligand 3, as their Ki values dropped to submicromolar range, respectively.
Measurement: Ki = 15.3 nM (pChEMBL 7.820000171661377)
Descriptors: MW 642.84, ALogP 6.7, HBA 7, HBD 2, PSA 101.38, QED 0.28
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2ccc(C(F)(F)C(F)(F)F)cc2Oc2ccc(F)cc2Cl)cc1
InChIKey: BAVGXISUWOMPHG-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 503.78, ALogP 6.88, HBA 3, HBD 2, PSA 75.63, QED 0.36
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2ccc(C(F)(F)C(F)(F)F)cc2Oc2ccc(F)cc2F)cc1
InChIKey: LLGVNUHNAGGBMF-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 487.33, ALogP 6.36, HBA 3, HBD 2, PSA 75.63, QED 0.4
Compound (SMILES): Cc1cc(F)ccc1Oc1cc(C(F)(F)C(F)(F)F)ccc1C(=O)Nc1ccc(C(=O)O)cc1
InChIKey: AFMYVWVPIHWHLQ-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 483.36, ALogP 6.53, HBA 3, HBD 2, PSA 75.63, QED 0.39
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2ccc(C(F)(F)F)cc2Oc2ccc(F)cc2Cl)cc1
InChIKey: CAROJXJPUIPNPU-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 453.77, ALogP 6.24, HBA 3, HBD 2, PSA 75.63, QED 0.45
Compound (SMILES): Cc1cc(F)ccc1Oc1cc(C(F)(F)F)ccc1C(=O)Nc1ccc(C(=O)O)cc1
InChIKey: WHSJMGMHKHPGIL-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 433.36, ALogP 5.9, HBA 3, HBD 2, PSA 75.63, QED 0.49
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2ccc(C(F)(F)F)cc2Oc2ccc(F)cc2F)cc1
InChIKey: MRBUJXKMAOIITA-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 437.32, ALogP 5.73, HBA 3, HBD 2, PSA 75.63, QED 0.5
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2ccc(C(F)(F)F)cc2Oc2ccc(OC(F)(F)F)cc2)cc1
InChIKey: CCFLCDDJGGMPDK-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 485.34, ALogP 6.35, HBA 4, HBD 2, PSA 84.86, QED 0.4
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2c(Oc3ccc(F)cc3F)cc(C(F)(F)F)cc2C(F)(F)F)cc1
InChIKey: MZIVXQQTMDYTAZ-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 405 nM (pChEMBL 6.389999866485596)
Descriptors: MW 505.32, ALogP 6.75, HBA 3, HBD 2, PSA 75.63, QED 0.38
Compound (SMILES): Cc1cc(F)ccc1Oc1cc(C(F)(F)F)cc(C(F)(F)F)c1C(=O)Nc1ccc(C(=O)O)cc1
InChIKey: IZPCPMZRYGDVDG-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 501.35, ALogP 6.91, HBA 3, HBD 2, PSA 75.63, QED 0.37
Compound (SMILES): COc1cc(F)ccc1Oc1cc(C(F)(F)F)cc(C(F)(F)F)c1C(=O)Nc1ccc(C(=O)O)cc1
InChIKey: ZYORVEKORXNUEM-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 517.35, ALogP 6.61, HBA 4, HBD 2, PSA 84.86, QED 0.36
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2c(Oc3ccc(F)cc3)cc(C(F)(F)F)cc2C(F)(F)F)cc1
InChIKey: FOTNRCKKBGVZMV-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 305 nM (pChEMBL 6.519999980926514)
Descriptors: MW 487.33, ALogP 6.61, HBA 3, HBD 2, PSA 75.63, QED 0.4
Compound (SMILES): COc1cc(F)ccc1Oc1cc(Cl)c(Cl)cc1C(=O)Nc1ccc(C(=O)O)cc1
InChIKey: JPVADBDXDGHZBJ-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 450.25, ALogP 5.88, HBA 4, HBD 2, PSA 84.86, QED 0.49
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(Cl)c(Cl)cc2Oc2ccc(F)cc2)cc1
InChIKey: MECYBMKMICVTAK-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 420.22, ALogP 5.88, HBA 3, HBD 2, PSA 75.63, QED 0.54
Compound (SMILES): Cc1cc(F)ccc1Oc1cc(Cl)c(Cl)cc1C(=O)Nc1ccc(C(=O)O)cc1
InChIKey: OFOIUNYHRNAMCV-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 434.25, ALogP 6.18, HBA 3, HBD 2, PSA 75.63, QED 0.5
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(Cl)c(Cl)cc2Oc2ccccc2)cc1
InChIKey: NEALAIJHPXEQSU-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 402.23, ALogP 5.74, HBA 3, HBD 2, PSA 75.63, QED 0.57
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(Cl)c(Cl)cc2Oc2ccc(CO)cc2F)cc1
InChIKey: FBQXWSUIRQKKRY-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 450.25, ALogP 5.37, HBA 4, HBD 3, PSA 95.86, QED 0.47
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(Cl)c(Cl)cc2Oc2ccc(OCC(F)(F)F)cc2)cc1
InChIKey: DZORGHOZKZHPLX-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Electrophysiology Assay: Patch clamp electrophysiology was used to assess the efficacy and selectivity of sodium channel blockers in dorsal root ganglion neurons. Rat neurons were isolated from the dorsal root ganglions and maintained in culture for 2 to 10 days in the presence of NGF (50 ng/ml) (culture media consisted of NeurobasalA supplemented with B27, glutamine and antibiotics). Small diameter neurons (nociceptors, 8-12 μm in diameter) were visually identified and probed with fine tip glass electrodes connected to an amplifier (Axon Instruments). The voltage clamp mode was used to assess the compound's IC50 holding the cells at −60 mV. In addition, the current clamp mode was employed to test the efficacy of the compounds in blocking action potential generation in response to current injections. The results of these experiments contributed to the definition of the efficacy profile of the compounds.
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 500.26, ALogP 6.68, HBA 4, HBD 2, PSA 84.86, QED 0.38