lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCOC4CCCCC43)nc3cc(-c4n[nH]c(=O)o4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: NDSBBPYRNSOZKT-YTFADCBGSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 564.09, ALogP 5.46, HBA 9, HBD 1, PSA 114.96, QED 0.34
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCO[C@H]4CCC[C@@H]43)nc3cc(-c4n[nH]c(=O)o4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: RENWZTRUVXXHGH-DODAUVCRSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 550.06, ALogP 5.07, HBA 9, HBD 1, PSA 114.96, QED 0.37
Compound (SMILES): C[C@H]1COC[C@H](C)N1c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C[C@H]1CC[C@H](C)CC1
InChIKey: GYLYIDFBMXCJNP-XSLAGTTESA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 538.05, ALogP 4.93, HBA 9, HBD 1, PSA 114.96, QED 0.38
Compound (SMILES): O=C(NCc1ccccn1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: XIKBBDZPWPLOFN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 441.54, ALogP 3.52, HBA 6, HBD 1, PSA 74.5, QED 0.47
Compound (SMILES): O=C(Nc1ccc(N2CCOCC2)cc1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: XWUPROYFXZAWOD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 511.63, ALogP 4.28, HBA 7, HBD 1, PSA 74.08, QED 0.4
Compound (SMILES): O=C(NC1CCN(c2ccccc2)CC1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: CIHLCQQNJXQNIW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.52 nM (pChEMBL 9.279999732971191)
Descriptors: MW 509.65, ALogP 4.59, HBA 6, HBD 1, PSA 64.85, QED 0.39
Compound (SMILES): CS(=O)(=O)c1ccc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)cc1
InChIKey: SLNHQLGUTOBGID-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 518.64, ALogP 3.53, HBA 7, HBD 1, PSA 95.75, QED 0.38
Compound (SMILES): Cn1cnc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)c1
InChIKey: UJXLXQFGNRFHSK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 444.54, ALogP 2.86, HBA 7, HBD 1, PSA 79.43, QED 0.47
Compound (SMILES): CC(=O)N1CCC(NC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)CC1
InChIKey: WEEPNTJUAXCUFN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 475.59, ALogP 2.93, HBA 6, HBD 1, PSA 81.92, QED 0.59
Compound (SMILES): CC(NC(=O)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1)c1ccccn1
InChIKey: ZMQQTGKVVFPDSJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 455.56, ALogP 4.08, HBA 6, HBD 1, PSA 74.5, QED 0.45
Compound (SMILES): O=C(NC1CCN(c2ncccc2Cl)CC1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: SBXVIUHANNPIPC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 545.09, ALogP 4.64, HBA 7, HBD 1, PSA 77.74, QED 0.36
Compound (SMILES): N#Cc1ccc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)cc1
InChIKey: VRJKPPUSDZXOLR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.44 nM (pChEMBL 9.359999656677246)
Descriptors: MW 465.56, ALogP 3.99, HBA 6, HBD 1, PSA 85.4, QED 0.44
Compound (SMILES): O=C(NCc1ccc2c(c1)OCO2)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: WKFLHPZCSXAWKK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.89 nM (pChEMBL 9.050000190734863)
Descriptors: MW 484.56, ALogP 3.85, HBA 7, HBD 1, PSA 80.07, QED 0.43
Compound (SMILES): CN(C)C(=O)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: MKTRMPIBOZYXTR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 378.48, ALogP 2.89, HBA 5, HBD 0, PSA 52.82, QED 0.68
Compound (SMILES): CNC(=O)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: FMLPGGANFIDSPV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.88 nM (pChEMBL 9.0600004196167)
Descriptors: MW 364.45, ALogP 2.55, HBA 5, HBD 1, PSA 61.61, QED 0.75
Compound (SMILES): O=C(NC1CC1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: UIKPTRHFTPOLFD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 390.49, ALogP 3.08, HBA 5, HBD 1, PSA 61.61, QED 0.7
Compound (SMILES): O=C(NC1CC(F)(F)C1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: OCUWZISPCUGWIM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 440.49, ALogP 3.72, HBA 5, HBD 1, PSA 61.61, QED 0.63
Compound (SMILES): O=C(c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1)N1CCC1
InChIKey: ADPQAJXGMQOWHJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 390.49, ALogP 3.04, HBA 5, HBD 0, PSA 52.82, QED 0.67
Compound (SMILES): O=C(c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1)N1CCCC1
InChIKey: ZXSHOERJJDKLRL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 404.51, ALogP 3.43, HBA 5, HBD 0, PSA 52.82, QED 0.65
Compound (SMILES): CS(=O)(=O)Cc1ccc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)cc1
InChIKey: KRXGOHJXVLYVSO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 532.67, ALogP 3.67, HBA 7, HBD 1, PSA 95.75, QED 0.35
Compound (SMILES): COc1cccc(CCNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)c1
InChIKey: XZAFUXOIMPHIRT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 484.6, ALogP 4.17, HBA 6, HBD 1, PSA 70.84, QED 0.38
Compound (SMILES): CN(Cc1cccc(S(C)(=O)=O)c1)C(=O)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: BGPFUQDEHMKOKJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.99 nM (pChEMBL 9)
Descriptors: MW 532.67, ALogP 3.87, HBA 7, HBD 0, PSA 86.96, QED 0.34
Compound (SMILES): N#Cc1ccc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)cn1
InChIKey: AUKYRYHMNPCTOO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 466.55, ALogP 3.39, HBA 7, HBD 1, PSA 98.29, QED 0.45
Compound (SMILES): CN(Cc1cccnc1)C(=O)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: ICBLNAUTYHYELQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 455.56, ALogP 3.86, HBA 6, HBD 0, PSA 65.71, QED 0.42
Compound (SMILES): N#Cc1cccc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)c1
InChIKey: GGYONIYRPREPSV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.91 nM (pChEMBL 9.039999961853027)
Descriptors: MW 465.56, ALogP 3.99, HBA 6, HBD 1, PSA 85.4, QED 0.44
Compound (SMILES): O=C(c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1)N1CCN(c2nccs2)CC1
InChIKey: HIJXAWSRTHSZGL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 502.64, ALogP 3.61, HBA 8, HBD 0, PSA 68.95, QED 0.4
Compound (SMILES): COc1cccnc1N1CCC(NC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)CC1
InChIKey: NUIGHKXXFRPUQF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.56 nM (pChEMBL 9.25)
Descriptors: MW 540.67, ALogP 3.99, HBA 8, HBD 1, PSA 86.97, QED 0.36
Compound (SMILES): CN(Cc1ccccn1)C(=O)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: JUHQRDJLVVSGKB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 455.56, ALogP 3.86, HBA 6, HBD 0, PSA 65.71, QED 0.42
Compound (SMILES): COc1cccc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)c1
InChIKey: HPURDCLYNFCGMW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.91 nM (pChEMBL 9.039999961853027)
Descriptors: MW 470.57, ALogP 4.13, HBA 6, HBD 1, PSA 70.84, QED 0.42
Compound (SMILES): O=C(NC1(c2ccccn2)CC1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: KHASMTXBVQUBQG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 467.57, ALogP 4.01, HBA 6, HBD 1, PSA 74.5, QED 0.44
Compound (SMILES): COc1ccc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)cc1
InChIKey: IFHAHZILAKZVRV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 470.57, ALogP 4.13, HBA 6, HBD 1, PSA 70.84, QED 0.42
Compound (SMILES): Cc1ccnc(CCNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)n1
InChIKey: TYRJMRWNDANHBQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 470.58, ALogP 3.26, HBA 7, HBD 1, PSA 87.39, QED 0.42
Compound (SMILES): Cn1cnc(CCNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)c1
InChIKey: DSUAZJYMKNDROE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 458.57, ALogP 2.9, HBA 7, HBD 1, PSA 79.43, QED 0.44
Compound (SMILES): O=C(NCC1CCOCC1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: HXHWHRCDMIUTPR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 448.57, ALogP 3.35, HBA 6, HBD 1, PSA 70.84, QED 0.6
Compound (SMILES): CC(C)Cn1cc(C(C)(C)C)s/c1=N\C(=O)c1cc(Br)ccc1OC[C@@H]1CCCN1C
InChIKey: RPSJSJZDPRLONT-RHGYLGJDSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QZN9
Assay: Radioligand Binding Assays: The CB1 and CB2 radioligand binding assays described herein are utilized to ascertain the selectivity of compounds of the present application for binding to CB2 relative to CB1 receptors.HEK293 cells stably expressing human CB2 receptors were grown until a confluent monolayer was formed. Briefly, the cells were harvested and homogenized in TE buffer (50 mM Tris-HCl, 1 mM MgCl2, and 1 mM EDTA) using a polytron for 210 second bursts in the presence of protease inhibitors, followed by centrifugation at 45,000xg for 20 minutes. The final membrane pellet was re-homogenized in storage buffer (50 mM Tris-HCl, 1 mM MgCl2, and 1 mM EDTA and 10% sucrose) and frozen at -78 C. until used. Saturation binding reactions were initiated by the addition of membrane preparation (protein concentration of 5 ug/well for human CB2) into wells of a deep well plate containing [3H]CP 55,940 (120 Ci/mmol, a nonselective CB agonist commercially available from Tocris) in assay buffer.
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 508.53, ALogP 5.48, HBA 5, HBD 0, PSA 46.83, QED 0.52
Compound (SMILES): CCCCn1cc(C(C)(C)C)s/c1=N\C(=O)c1cc(Cl)ccc1OCC(N)=O
InChIKey: LFVMBZLELINMSN-NMWGTECJSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QZN9
Assay: Radioligand Binding Assays: The CB1 and CB2 radioligand binding assays described herein are utilized to ascertain the selectivity of compounds of the present application for binding to CB2 relative to CB1 receptors.HEK293 cells stably expressing human CB2 receptors were grown until a confluent monolayer was formed. Briefly, the cells were harvested and homogenized in TE buffer (50 mM Tris-HCl, 1 mM MgCl2, and 1 mM EDTA) using a polytron for 210 second bursts in the presence of protease inhibitors, followed by centrifugation at 45,000xg for 20 minutes. The final membrane pellet was re-homogenized in storage buffer (50 mM Tris-HCl, 1 mM MgCl2, and 1 mM EDTA and 10% sucrose) and frozen at -78 C. until used. Saturation binding reactions were initiated by the addition of membrane preparation (protein concentration of 5 ug/well for human CB2) into wells of a deep well plate containing [3H]CP 55,940 (120 Ci/mmol, a nonselective CB agonist commercially available from Tocris) in assay buffer.
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 423.97, ALogP 3.91, HBA 5, HBD 1, PSA 86.68, QED 0.73
Compound (SMILES): CC(C)Cn1cc(C(C)(C)C)s/c1=N\C(=O)c1cc(C(F)(F)F)ccc1OCc1ccco1
InChIKey: YDAZFURDNJJCIQ-SLMZUGIISA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Radioligand Binding Assays: The CB1 and CB2 radioligand binding assays described herein are utilized to ascertain the selectivity of compounds of the present application for binding to CB2 relative to CB1 receptors.HEK293 cells stably expressing human CB2 receptors were grown until a confluent monolayer was formed. Briefly, the cells were harvested and homogenized in TE buffer (50 mM Tris-HCl, 1 mM MgCl2, and 1 mM EDTA) using a polytron for 210 second bursts in the presence of protease inhibitors, followed by centrifugation at 45,000xg for 20 minutes. The final membrane pellet was re-homogenized in storage buffer (50 mM Tris-HCl, 1 mM MgCl2, and 1 mM EDTA and 10% sucrose) and frozen at -78 C. until used. Saturation binding reactions were initiated by the addition of membrane preparation (protein concentration of 5 ug/well for human CB2) into wells of a deep well plate containing [3H]CP 55,940 (120 Ci/mmol, a nonselective CB agonist commercially available from Tocris) in assay buffer.
Measurement: Ki = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 480.55, ALogP 6.44, HBA 5, HBD 0, PSA 56.73, QED 0.41