lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(Nc1ccc(F)cc1C(=O)N1CCC1)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: BXTXRBORNVEZHZ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 433.45, ALogP 3.12, HBA 7, HBD 2, PSA 113, QED 0.61
Compound (SMILES): CC(C)(O)CNC(=O)c1cc(F)ccc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: DKHUXWWHAPJDSP-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 465.49, ALogP 2.78, HBA 8, HBD 4, PSA 142.02, QED 0.4
Compound (SMILES): CNC(=O)c1c(F)cccc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: XQZJQTKSDPCHFO-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 68.6 nM (pChEMBL 7.159999847412109)
Descriptors: MW 407.41, ALogP 2.64, HBA 7, HBD 3, PSA 121.79, QED 0.57
Compound (SMILES): CN(C)C(=O)c1c(F)cccc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: GTSAWIOETMNSRV-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 421.44, ALogP 2.98, HBA 7, HBD 2, PSA 113, QED 0.63
Compound (SMILES): O=C(Nc1cccc(F)c1C(=O)N1CCC1)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: VNUZCDYOZMMLPN-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 433.45, ALogP 3.12, HBA 7, HBD 2, PSA 113, QED 0.61
Compound (SMILES): CC(C)(O)CNC(=O)c1c(F)cccc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: XPOBDYLFMFENHF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 465.49, ALogP 2.78, HBA 8, HBD 4, PSA 142.02, QED 0.4
Compound (SMILES): CCN(C)c1cnc(Nc2cncnc2)c(C(=O)Nc2cnn(C)c2C(=O)NC)n1
InChIKey: BVCYGRQXRQRGDZ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 20.5 nM (pChEMBL 7.690000057220459)
Descriptors: MW 410.44, ALogP 0.81, HBA 10, HBD 3, PSA 142.85, QED 0.52
Compound (SMILES): CNC(=O)c1cc(F)ccc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: TZAFGKFLPAETHV-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 407.41, ALogP 2.64, HBA 7, HBD 3, PSA 121.79, QED 0.57
Compound (SMILES): CN(C)CCNC(=O)c1c(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)cnn1C
InChIKey: GMLVNJUPLCMOSC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 450.51, ALogP 1.16, HBA 10, HBD 3, PSA 142.85, QED 0.44
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(C3CC3)ncc2Nc2cncnc2)cnn1C
InChIKey: HBBFOWGNRARUQI-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 34.3 nM (pChEMBL 7.460000038146973)
Descriptors: MW 393.41, ALogP 1.23, HBA 9, HBD 3, PSA 139.61, QED 0.57
Compound (SMILES): CN1CC(NC(=O)c2c(NC(=O)c3nc(C4CC4)cnc3Nc3cncnc3)cnn2C)C1
InChIKey: GEEDHFJOHKDCCZ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 11.1 nM (pChEMBL 7.960000038146973)
Descriptors: MW 448.49, ALogP 0.92, HBA 10, HBD 3, PSA 142.85, QED 0.48
Compound (SMILES): CN(C)C(=O)c1c(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)ccc(F)c1F
InChIKey: AUPFRAGEKZESMS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 24.1 nM (pChEMBL 7.619999885559082)
Descriptors: MW 439.43, ALogP 3.12, HBA 7, HBD 2, PSA 113, QED 0.61
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)ccc(F)c1F
InChIKey: QDHMOAXJQWJLGM-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 425.4, ALogP 2.78, HBA 7, HBD 3, PSA 121.79, QED 0.56
Compound (SMILES): CC(C)(O)CNC(=O)c1c(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)ccc(F)c1F
InChIKey: VZPIOXXKSRFQNI-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 483.48, ALogP 2.92, HBA 8, HBD 4, PSA 142.02, QED 0.38
Compound (SMILES): O=C(Nc1ccc(F)c(F)c1C(=O)N1CCC1)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: DTMAFEPYFLKNNQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 451.44, ALogP 3.26, HBA 7, HBD 2, PSA 113, QED 0.59
Compound (SMILES): O=C(Nc1c(C(=O)N2CCC2)ccc(F)c1F)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: BLEDRZXVUCXCDG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 86.3 nM (pChEMBL 7.059999942779541)
Descriptors: MW 451.44, ALogP 3.26, HBA 7, HBD 2, PSA 113, QED 0.59
Compound (SMILES): CCOC(=O)CCc1ccc(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)c(C(=O)NC)c1
InChIKey: RTDCAEHFYAPNFR-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 489.54, ALogP 3, HBA 9, HBD 3, PSA 148.09, QED 0.37
Compound (SMILES): CNC(=O)COc1ccc(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)c(C(=O)NC)c1
InChIKey: CGYNNCXAJYUIML-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 476.5, ALogP 1.62, HBA 9, HBD 4, PSA 160.12, QED 0.36
Compound (SMILES): O=C(Nc1cc(F)cc(F)c1C(=O)N1CCC1)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: ZRWDPWVPVCFZOZ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 35.9 nM (pChEMBL 7.449999809265137)
Descriptors: MW 451.44, ALogP 3.26, HBA 7, HBD 2, PSA 113, QED 0.59
Compound (SMILES): CC(C)(O)CNC(=O)c1c(F)cc(F)cc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: VHVYQUTYCGRKBJ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 483.48, ALogP 2.92, HBA 8, HBD 4, PSA 142.02, QED 0.38
Compound (SMILES): CN(C)C(=O)c1ccc(F)c(F)c1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: AQAZIPYKMRRUDG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 335.3 nM (pChEMBL 6.46999979019165)
Descriptors: MW 439.43, ALogP 3.12, HBA 7, HBD 2, PSA 113, QED 0.61
Compound (SMILES): CC(C)(O)CNC(=O)c1ccc(F)c(F)c1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: XFLGXNVANTUXHA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 483.48, ALogP 2.92, HBA 8, HBD 4, PSA 142.02, QED 0.38
Compound (SMILES): CNC(=O)c1ccc(F)c(F)c1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: OTTXABBSBZYSLV-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 425.4, ALogP 2.78, HBA 7, HBD 3, PSA 121.79, QED 0.56
Compound (SMILES): CNC(=O)c1cc(CCC(=O)O)ccc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: DBNDSDTWULRLLN-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 461.48, ALogP 2.52, HBA 8, HBD 4, PSA 159.09, QED 0.38
Compound (SMILES): CC(C)c1ncc(Nc2cncnc2)c(C(=O)Nc2cccnc2C(=O)NCC(C)(C)O)n1
InChIKey: VQTMSSPIHOWVBQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 450.5, ALogP 2.28, HBA 9, HBD 4, PSA 154.91, QED 0.4
Compound (SMILES): CC(C)(O)CNC(=O)c1ncccc1NC(=O)c1nc(C(C)(C)C)ncc1Nc1cncnc1
InChIKey: LKTPZAZGKCIHHM-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 464.53, ALogP 2.46, HBA 9, HBD 4, PSA 154.91, QED 0.41
Compound (SMILES): CC(C)Cc1ncc(Nc2cncnc2)c(C(=O)Nc2cccnc2C(=O)NCC(C)(C)O)n1
InChIKey: NSJHAZMNAMSDRI-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 464.53, ALogP 2.36, HBA 9, HBD 4, PSA 154.91, QED 0.37
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(CC(C)C)ncc2Nc2cncnc2)cnn1C
InChIKey: ZNRCWSKIIMIJIB-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 409.45, ALogP 1.55, HBA 9, HBD 3, PSA 139.61, QED 0.53
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(N3CCN(C)CC3)cnc2Nc2cncnc2)cnn1C
InChIKey: AAQKHBVPOQJDPA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 690.8 nM (pChEMBL 6.159999847412109)
Descriptors: MW 451.5, ALogP 0.11, HBA 11, HBD 3, PSA 146.09, QED 0.47
Compound (SMILES): CON(C)C(=O)c1c(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)cnn1C
InChIKey: BLSFJBNWJQFWES-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 423.44, ALogP 1.51, HBA 10, HBD 2, PSA 140.05, QED 0.54
Compound (SMILES): Cn1ncc(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)c1C(=O)N1CCCO1
InChIKey: QTTKVJJYXLZWQW-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 435.45, ALogP 1.65, HBA 10, HBD 2, PSA 140.05, QED 0.59
Compound (SMILES): Cn1ncc(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)c1C(=O)NC1CCCC1O
InChIKey: WWAJEEJGLXUWLL-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 463.5, ALogP 1.52, HBA 10, HBD 4, PSA 159.84, QED 0.41
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(OCC(F)(F)F)ncc2Nc2cncnc2)cnn1C
InChIKey: BAPHDIMPQQRWRB-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 126.2 nM (pChEMBL 6.900000095367432)
Descriptors: MW 451.37, ALogP 1.3, HBA 10, HBD 3, PSA 148.84, QED 0.48
Compound (SMILES): CNC(=O)c1cc(OCC(C)(C)O)ccc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: BJXDTXDRKYIJRV-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 477.53, ALogP 2.65, HBA 9, HBD 4, PSA 151.25, QED 0.36
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(OCC(F)(F)F)cnc2Nc2cncnc2)cnn1C
InChIKey: WIHKTQSSNSFXBG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 49.3 nM (pChEMBL 7.309999942779541)
Descriptors: MW 451.37, ALogP 1.3, HBA 10, HBD 3, PSA 148.84, QED 0.48
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(C(C)(C)O)ncc2Nc2cncnc2)cnn1C
InChIKey: IWKBNAOSOZCEEX-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 250.4 nM (pChEMBL 6.599999904632568)
Descriptors: MW 411.43, ALogP 0.58, HBA 10, HBD 4, PSA 159.84, QED 0.45
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(C(C)(C)O)cnc2Nc2cncnc2)cnn1C
InChIKey: OPLXPHTWELKCRO-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 411.43, ALogP 0.58, HBA 10, HBD 4, PSA 159.84, QED 0.45
Compound (SMILES): COc1ccc(CNC(=O)c2cc(-c3cc(C)cc(C)c3)nnc2-c2cnn(C)c2)cc1OC
InChIKey: XYOYIYUMFYCMFA-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: For each antagonist, IC50 value (the concentration of compound needed to inhibit 50% of the agonist response) is determined Alternatively, compound potency can be assessed by a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430) in which the inhibition constant (Ki) is determined in membranes prepared from CHO cells expressing either the OX1 or OX2 receptor. The intrinsic orexin receptor antagonist activity of a compound which may be used in the present invention may be determined by these assays.
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 457.53, ALogP 4.11, HBA 7, HBD 1, PSA 91.16, QED 0.45
Compound (SMILES): COc1ccc(CNC(=O)c2cc(-c3cc(C)cc(Cl)c3)nnc2N2CCOCC2)cc1OC
InChIKey: INCOCCLBSPRBNS-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: For each antagonist, IC50 value (the concentration of compound needed to inhibit 50% of the agonist response) is determined Alternatively, compound potency can be assessed by a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430) in which the inhibition constant (Ki) is determined in membranes prepared from CHO cells expressing either the OX1 or OX2 receptor. The intrinsic orexin receptor antagonist activity of a compound which may be used in the present invention may be determined by these assays.
Measurement: Ki = 0.96 nM (pChEMBL 9.020000457763672)
Descriptors: MW 482.97, ALogP 3.89, HBA 7, HBD 1, PSA 85.81, QED 0.55
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: YTHUQGIGAIZNIM-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 519.65, ALogP 5.08, HBA 7, HBD 2, PSA 86.28, QED 0.37
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C(=O)OC(C)(C)C)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: PDJFRJFTKGLDDM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 2044 nM (pChEMBL 5.690000057220459)
Descriptors: MW 605.74, ALogP 6.38, HBA 8, HBD 2, PSA 112.58, QED 0.26
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCNCC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: SZPKERXOPUWUPW-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 505.63, ALogP 4.74, HBA 7, HBD 3, PSA 95.07, QED 0.35
Compound (SMILES): CCN1CCN(C2CCc3cc(C(=O)Nc4ccc(C)c(Nc5nccc(-c6cccnc6)n5)c4)ccc32)CC1
InChIKey: JVGNHFZOVWJKER-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 533.68, ALogP 5.47, HBA 7, HBD 2, PSA 86.28, QED 0.33
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C(C)C)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: PZINVJUNZRLUIM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 547.71, ALogP 5.86, HBA 7, HBD 2, PSA 86.28, QED 0.3
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(CCO)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: JXVHQHBMOSSYBX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 549.68, ALogP 4.44, HBA 8, HBD 3, PSA 106.51, QED 0.3
Compound (SMILES): CC(=O)N1CCN(C2CCc3cc(C(=O)Nc4ccc(C)c(Nc5nccc(-c6cccnc6)n5)c4)ccc32)CC1
InChIKey: AJIVJAKIEIICSU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 411 nM (pChEMBL 6.389999866485596)
Descriptors: MW 547.66, ALogP 4.99, HBA 7, HBD 2, PSA 103.35, QED 0.35
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C)CC2)cc1Nc1nccc(-c2cncnc2)n1
InChIKey: IQOAIXAFDYRGNK-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 520.64, ALogP 4.47, HBA 8, HBD 2, PSA 99.17, QED 0.38