lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)Nc1ccc(Nc2nc3ccccc3nc2NS(=O)(=O)c2ccc(C)cc2)cc1
InChIKey: YCSQUMADCPEGTB-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 10552 nM (pChEMBL 4.980000019073486)
Descriptors: MW 447.52, ALogP 4.44, HBA 6, HBD 3, PSA 113.08, QED 0.4
Compound (SMILES): CN1CC2C[C@@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: MBFDPIYMOIZLLZ-ACGXKRRESA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 242.15, ALogP 3.2, HBA 1, HBD 0, PSA 3.24, QED 0.73
Compound (SMILES): CN1CC2C[C@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: MBFDPIYMOIZLLZ-FFFFSGIJSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 242.15, ALogP 3.2, HBA 1, HBD 0, PSA 3.24, QED 0.73
Compound (SMILES): CCN1CC2C[C@@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: YCEPPWZMXQMHRV-HQVZTVAUSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 256.18, ALogP 3.59, HBA 1, HBD 0, PSA 3.24, QED 0.78
Compound (SMILES): CCN1CC2C[C@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: YCEPPWZMXQMHRV-JLOHTSLTSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 256.18, ALogP 3.59, HBA 1, HBD 0, PSA 3.24, QED 0.78
Compound (SMILES): CCCN1CC2CC2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: CBICSBDJSHIILP-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 270.2, ALogP 3.98, HBA 1, HBD 0, PSA 3.24, QED 0.8
Compound (SMILES): CCCN1CC2C[C@@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: CBICSBDJSHIILP-IAXJKZSUSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 270.2, ALogP 3.98, HBA 1, HBD 0, PSA 3.24, QED 0.8
Compound (SMILES): CCCN1CC2C[C@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: CBICSBDJSHIILP-SBXXRYSUSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 270.2, ALogP 3.98, HBA 1, HBD 0, PSA 3.24, QED 0.8
Compound (SMILES): CCCCN1CC2CC2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: ARMJFBWEHFAODY-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 284.23, ALogP 4.37, HBA 1, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): CCCCN1CC2C[C@@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: ARMJFBWEHFAODY-CVRLYYSRSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 284.23, ALogP 4.37, HBA 1, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): CCCCN1CC2C[C@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: ARMJFBWEHFAODY-WPZCJLIBSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 284.23, ALogP 4.37, HBA 1, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): CC(C)CN1CC2CC2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: GJNUJXJSBQTLMX-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 284.23, ALogP 4.22, HBA 1, HBD 0, PSA 3.24, QED 0.8
Compound (SMILES): CC(C)N1CC2CC2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: HYTFHLKGMUVBOD-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 270.2, ALogP 3.98, HBA 1, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): CC(C)N1CC2C[C@@]2(c2ccc(Cl)c(Cl)c2)C1
InChIKey: HYTFHLKGMUVBOD-IAXJKZSUSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Binding Assay: Binding assay using NET, DAT and SERT enzyme.
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 270.2, ALogP 3.98, HBA 1, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): CCc1n[nH]c2c1CN(c1ncnn3c(C)nc(C4CCOCC4)c13)CC2
InChIKey: NCJUUCRCQKTSML-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.959 nM (pChEMBL 9.020000457763672)
Descriptors: MW 367.46, ALogP 2.17, HBA 7, HBD 1, PSA 84.23, QED 0.76
Compound (SMILES): Cc1nc(C2CCOCC2)c2c(N3CCc4[nH]nc(C(C)C)c4C3)ncnn12
InChIKey: UXFMETYQZLJLBQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.902 nM (pChEMBL 9.039999961853027)
Descriptors: MW 381.48, ALogP 2.74, HBA 7, HBD 1, PSA 84.23, QED 0.75
Compound (SMILES): Cc1nc(-c2ccccc2F)c2c(N3CCn4ncc(C(F)(F)F)c4C3)ncnn12
InChIKey: UFJJAEIFRMPPHX-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 1.73 nM (pChEMBL 8.760000228881836)
Descriptors: MW 417.37, ALogP 3.47, HBA 7, HBD 0, PSA 64.14, QED 0.47
Compound (SMILES): Cc1nc(-c2ccccc2F)c2c(N3CCc4ncncc4C3)ncnn12
InChIKey: YKCJUYLUUDVLJK-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 361.38, ALogP 2.59, HBA 7, HBD 0, PSA 72.1, QED 0.55
Compound (SMILES): Cc1ncc2c(n1)CCN(c1ncnn3c(C)nc(-c4ccccc4F)c13)C2
InChIKey: ZAXBZHWQTXDADR-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 18.6 nM (pChEMBL 7.730000019073486)
Descriptors: MW 375.41, ALogP 2.9, HBA 7, HBD 0, PSA 72.1, QED 0.54
Compound (SMILES): CCc1c2c(nn1C)CCN(c1ncnn3c(C)nc(-c4ccccc4F)c13)C2
InChIKey: VXPFYTLYXUNGJO-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.147 nM (pChEMBL 9.829999923706055)
Descriptors: MW 391.45, ALogP 3.1, HBA 7, HBD 0, PSA 64.14, QED 0.54
Compound (SMILES): Cc1c2c(nn1C)CCN(c1ncnn3c(C)nc(-c4ccccc4F)c13)C2
InChIKey: AMXUNCQOHMEKKO-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.638 nM (pChEMBL 9.199999809265137)
Descriptors: MW 377.43, ALogP 2.84, HBA 7, HBD 0, PSA 64.14, QED 0.54
Compound (SMILES): Cc1nc2c(s1)CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: IFYNHWHPNSEXBN-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 1.49 nM (pChEMBL 8.829999923706055)
Descriptors: MW 380.45, ALogP 3.57, HBA 7, HBD 0, PSA 59.21, QED 0.53
Compound (SMILES): Cc1nn(C)c2c1CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: NMBOADHXCHYWOE-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.834 nM (pChEMBL 9.079999923706055)
Descriptors: MW 377.43, ALogP 2.84, HBA 7, HBD 0, PSA 64.14, QED 0.54
Compound (SMILES): Cc1nc(-c2ccccc2F)c2c(N3Cc4ccccc4CC3C)ncnn12
InChIKey: BVZHUSQLXALJRA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 8.01 nM (pChEMBL 8.100000381469727)
Descriptors: MW 373.44, ALogP 4.19, HBA 5, HBD 0, PSA 46.32, QED 0.53
Compound (SMILES): CCc1nn(C)c2c1CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: JDFBORTWMSETMR-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.336 nM (pChEMBL 9.470000267028809)
Descriptors: MW 391.45, ALogP 3.1, HBA 7, HBD 0, PSA 64.14, QED 0.54
Compound (SMILES): Cc1nc(-c2ccccc2F)c2c(N3CCc4c(c(C(F)(F)F)nn4C)C3)ncnn12
InChIKey: GZOJPZVQOHLUSG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 1.28 nM (pChEMBL 8.890000343322754)
Descriptors: MW 431.4, ALogP 3.55, HBA 7, HBD 0, PSA 64.14, QED 0.45
Compound (SMILES): CCc1nn(C)c2c1CN(c1ncnn3c(C)nc(-c4ccc(F)cc4Cl)c13)CC2
InChIKey: ORZFWUAYZNSYIY-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.519 nM (pChEMBL 9.289999961853027)
Descriptors: MW 425.9, ALogP 3.75, HBA 7, HBD 0, PSA 64.14, QED 0.5
Compound (SMILES): CCc1c2c(nn1C)CCN(c1ncnn3c(C)nc(-c4ccc(F)cc4Cl)c13)C2
InChIKey: NIVVZWLOFKZECQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.233 nM (pChEMBL 9.630000114440918)
Descriptors: MW 425.9, ALogP 3.75, HBA 7, HBD 0, PSA 64.14, QED 0.5
Compound (SMILES): Cc1nn(C)c2c1CN(c1ncnn3c(C)nc(-c4ccc(F)cc4Cl)c13)CC2
InChIKey: UKGPQUUBFLYOTR-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 1.35 nM (pChEMBL 8.869999885559082)
Descriptors: MW 411.87, ALogP 3.5, HBA 7, HBD 0, PSA 64.14, QED 0.5
Compound (SMILES): Cc1nc(-c2ccc(F)cc2Cl)c2c(N3CCc4cnn(C)c4C3)ncnn12
InChIKey: ATOXRSRTUIGIRQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 2.65 nM (pChEMBL 8.579999923706055)
Descriptors: MW 397.85, ALogP 3.19, HBA 7, HBD 0, PSA 64.14, QED 0.52
Compound (SMILES): CCOc1nc(C)nc2c1CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: MJXNCMIFEAJCSF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 1.43 nM (pChEMBL 8.850000381469727)
Descriptors: MW 419.46, ALogP 3.3, HBA 8, HBD 0, PSA 81.33, QED 0.5
Compound (SMILES): Cc1nc2c(c(=O)n1C)CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: GWOAUEMTLDKEIE-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 2.71 nM (pChEMBL 8.569999694824219)
Descriptors: MW 405.44, ALogP 2.2, HBA 8, HBD 0, PSA 81.21, QED 0.51
Compound (SMILES): Cc1nc2c(c(OC(F)F)n1)CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: CWLSKSGZALTUCL-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 441.42, ALogP 3.5, HBA 8, HBD 0, PSA 81.33, QED 0.48
Compound (SMILES): CCn1c(C)nc2c(c1=O)CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: ZQMAOFFNOKIBOH-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 1.19 nM (pChEMBL 8.920000076293945)
Descriptors: MW 419.46, ALogP 2.69, HBA 8, HBD 0, PSA 81.21, QED 0.51
Compound (SMILES): Cc1nc2c(c(=O)n1C)CN(c1ncnn3c(C)nc([C@@H]4CCOC4)c13)CC2
InChIKey: VYNYVRGBMLWHEF-CYBMUJFWSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 1.62 nM (pChEMBL 8.789999961853027)
Descriptors: MW 381.44, ALogP 0.9, HBA 9, HBD 0, PSA 90.44, QED 0.65
Compound (SMILES): CCn1c(C)nc2c(c1=O)CN(c1ncnn3c(C)nc([C@@H]4CCOC4)c13)CC2
InChIKey: OBRNLARPNKFQOP-CQSZACIVSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.0998 nM (pChEMBL 10)
Descriptors: MW 395.47, ALogP 1.38, HBA 9, HBD 0, PSA 90.44, QED 0.66
Compound (SMILES): Cc1nc(C)c2c(n1)CCN(c1ncnn3c(C)nc(-c4ccccc4F)c13)C2
InChIKey: XDWRLXHSUJWVMY-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 2.34 nM (pChEMBL 8.630000114440918)
Descriptors: MW 389.44, ALogP 3.21, HBA 7, HBD 0, PSA 72.1, QED 0.52
Compound (SMILES): CCc1nc(C)nc2c1CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: LFCHKMNFRYPXRL-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.456 nM (pChEMBL 9.34000015258789)
Descriptors: MW 403.47, ALogP 3.46, HBA 7, HBD 0, PSA 72.1, QED 0.52
Compound (SMILES): CCc1nc(C)nc2c1CN(c1ncnn3c(C)nc([C@@H]4CCOC4)c13)CC2
InChIKey: XIIJNVWHEATJOT-CQSZACIVSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 379.47, ALogP 2.16, HBA 8, HBD 0, PSA 81.33, QED 0.69
Compound (SMILES): Cc1ncc2c(n1)CCN(c1ncnn3c(C)nc([C@@H]4CCOC4)c13)C2
InChIKey: CKOQGSFWPNUHKS-CYBMUJFWSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 2.44 nM (pChEMBL 8.609999656677246)
Descriptors: MW 351.41, ALogP 1.6, HBA 8, HBD 0, PSA 81.33, QED 0.69
Compound (SMILES): COc1nc(C2CC2)nc2c1CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: NQVWEEHMBOBYGM-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 431.48, ALogP 3.48, HBA 8, HBD 0, PSA 81.33, QED 0.49
Compound (SMILES): CCc1nc(C2CC2)nc2c1CN(c1ncnn3c(C)nc(-c4ccccc4F)c13)CC2
InChIKey: LXLFSDFDUFLYMF-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.265 nM (pChEMBL 9.579999923706055)
Descriptors: MW 429.5, ALogP 4.03, HBA 7, HBD 0, PSA 72.1, QED 0.49
Compound (SMILES): CCc1nc(C2CC2)nc2c1CN(c1ncnn3c(C)nc([C@@H]4CCOC4)c13)CC2
InChIKey: WGFZLXFAMITYML-OAHLLOKOSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.0777 nM (pChEMBL 10.109999656677246)
Descriptors: MW 405.51, ALogP 2.73, HBA 8, HBD 0, PSA 81.33, QED 0.66
Compound (SMILES): Cc1ccc2c(n1)CCN(c1ncnn3c(C)nc(-c4ccccc4F)c13)C2
InChIKey: NRECROFMGVWREL-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.49 nM (pChEMBL 9.3100004196167)
Descriptors: MW 374.42, ALogP 3.5, HBA 6, HBD 0, PSA 59.21, QED 0.54
Compound (SMILES): Cc1ccc2c(n1)CCN(c1ncnn3c(C)nc([C@@H]4CCOC4)c13)C2
InChIKey: IKUXIHAPMKHTDP-OAHLLOKOSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay: The ability of a compound to inhibit PDE10 enzymatic activity can be demonstrated by any number of assays that are known in the art. The products of Examples 1-175 were tested in the assay described below.PDE10 activity was measured using a scintillation assay (SPA-based method) similar to that previously described by Seeger, T. F. et al., Brain Research 985 (2003) 113-126. The compounds' relative activity as PDE10 inhibitors was investigated by assaying a fixed amount of enzyme in the presence of the test compound and low substrate concentration (cAMP) such that an IC50 could be determined. More specifically, this assay uses a Scintillation Proximity Assay (SPA) to measure the inhibition of rat1 and human recombinant2 PDE10 enzyme activity by compounds in vitro (preparation of enzymes described below). The assay is performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH 7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE10.
Measurement: IC50 = 0.279 nM (pChEMBL 9.550000190734863)
Descriptors: MW 350.43, ALogP 2.2, HBA 7, HBD 0, PSA 68.44, QED 0.71