lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc2c(n1)CC[C@@H]2NC(=O)COc1cc(C(F)F)c2c(C3CC3)nn(C)c2n1
InChIKey: BEZZNQFBPGIIIH-INIZCTEOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 427.46, ALogP 3.67, HBA 6, HBD 1, PSA 81.93, QED 0.65
Compound (SMILES): COc1ccc2c(c1)CCC2NC(=O)COc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: NHKDZRLVFDFWKF-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 168 nM (pChEMBL 6.78000020980835)
Descriptors: MW 406.49, ALogP 3.35, HBA 6, HBD 1, PSA 78.27, QED 0.68
Compound (SMILES): Cc1ccc(C(C)(C)NC(=O)COc2cc(C)c3c(C4CC4)nn(C)c3n2)cc1
InChIKey: IEJCNGUGIZRCPY-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 392.5, ALogP 3.89, HBA 5, HBD 1, PSA 69.04, QED 0.69
Compound (SMILES): COc1ccc([C@H](C)NC(=O)COc2cc(C(F)F)c3c(C4CC4)nn(C)c3n2)cc1
InChIKey: HJFQNSLHQCRVOT-LBPRGKRZSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 430.46, ALogP 4.05, HBA 6, HBD 1, PSA 78.27, QED 0.58
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C(F)F)c3c(C4CC4)nn(C)c3n2)cc1
InChIKey: MJVATLQDOLXSMC-ZDUSSCGKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 414.46, ALogP 4.35, HBA 5, HBD 1, PSA 69.04, QED 0.62
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C(F)(F)F)c3c(C4CC4)nn(C)c3n2)cc1
InChIKey: FWHORWCXNOSXAZ-ZDUSSCGKSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 432.45, ALogP 4.43, HBA 5, HBD 1, PSA 69.04, QED 0.63
Compound (SMILES): COc1ccc(C(C)NC(=O)COc2cc(C(F)(F)F)c3c(C4CC4)nn(C)c3n2)cn1
InChIKey: UKGSBPIAOPOOHI-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 428 nM (pChEMBL 6.369999885559082)
Descriptors: MW 449.43, ALogP 3.52, HBA 7, HBD 1, PSA 91.16, QED 0.59
Compound (SMILES): COc1ccc([C@H](C)NC(=O)COc2cc(C(F)(F)F)c3c(C4CC4)nn(C)c3n2)cc1
InChIKey: UNNYCLWPHWRNEL-LBPRGKRZSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 448.45, ALogP 4.13, HBA 6, HBD 1, PSA 78.27, QED 0.59
Compound (SMILES): COc1ccc([C@H](C)NC(=O)COc2cc(C(F)F)c3c(-c4ccccc4)nn(C)c3n2)cc1
InChIKey: BKUJJMIDYHPYMQ-HNNXBMFYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 466.49, ALogP 4.84, HBA 6, HBD 1, PSA 78.27, QED 0.4
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C(F)F)c3c(-c4ccccc4)nn(C)c3n2)cc1
InChIKey: JQEYMZFGKKZWLJ-INIZCTEOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 450.49, ALogP 5.14, HBA 5, HBD 1, PSA 69.04, QED 0.42
Compound (SMILES): COc1ccc(C(C)NC(=O)COc2cc(C(F)F)c3c(-c4ccccc4)nn(C)c3n2)cn1
InChIKey: XUCPLVDEFHBGNJ-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 467.48, ALogP 4.23, HBA 7, HBD 1, PSA 91.16, QED 0.42
Compound (SMILES): COc1ccccc1-c1nn(C)c2nc(OCC(=O)N[C@@H](C)c3ccc(C)cc3)ccc12
InChIKey: REHNSFKMKFEDRD-KRWDZBQOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 430.51, ALogP 4.21, HBA 6, HBD 1, PSA 78.27, QED 0.48
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2ccc3c(C(C)(C)C)nn(C)c3n2)cc1
InChIKey: JMCOSVVYKIJWJT-HNNXBMFYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 164 nM (pChEMBL 6.789999961853027)
Descriptors: MW 380.49, ALogP 3.83, HBA 5, HBD 1, PSA 69.04, QED 0.73
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C)c3c(C(C)C)nn(C)c3n2)cc1
InChIKey: CITUDCOPJFTZRP-INIZCTEOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 380.49, ALogP 3.96, HBA 5, HBD 1, PSA 69.04, QED 0.7
Compound (SMILES): COc1ccc([C@H](C)NC(=O)COc2cc(C)c3c(-c4cc(C)oc4C)nn(C)c3n2)cc1
InChIKey: KQLLHRDEUYELHG-INIZCTEOSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 221 nM (pChEMBL 6.659999847412109)
Descriptors: MW 448.52, ALogP 4.42, HBA 7, HBD 1, PSA 91.41, QED 0.45
Compound (SMILES): Cc1cc(-c2nn(C)c3nc(OCC(=O)NC(C)c4c(C)nn(C)c4C)cc(C)c23)c(C)o1
InChIKey: LIKACLHWOBAKJP-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 450.54, ALogP 3.76, HBA 8, HBD 1, PSA 100, QED 0.48
Compound (SMILES): COc1ccc([C@H](C)NC(=O)COc2cc(C)c3c(-c4ccoc4C)nn(C)c3n2)cc1
InChIKey: DEGZXMGBKUNGPA-HNNXBMFYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 434.5, ALogP 4.11, HBA 7, HBD 1, PSA 91.41, QED 0.47
Compound (SMILES): COc1ccc([C@H](C)NC(=O)COc2cc(C)c3c(-c4cc(OC)cc(OC)c4)nn(C)c3n2)cc1
InChIKey: ATDRTNDYIVXCCF-KRWDZBQOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 490.56, ALogP 4.23, HBA 8, HBD 1, PSA 96.73, QED 0.38
Compound (SMILES): COc1ccnc(-c2nn(C)c3nc(OCC(=O)N[C@@H](C)c4ccc(C)cc4)cc(C)c23)c1
InChIKey: KUHPLWASZXQETH-KRWDZBQOSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 445.52, ALogP 3.91, HBA 7, HBD 1, PSA 91.16, QED 0.46
Compound (SMILES): Cc1ccc2c(n1)CC[C@@H]2NC(=O)COc1cc(C(F)F)c2c(-c3cc(C)oc3C)nn(C)c2n1
InChIKey: HGSOFDAPWKEOJR-IBGZPJMESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 271 nM (pChEMBL 6.570000171661377)
Descriptors: MW 481.5, ALogP 4.67, HBA 7, HBD 1, PSA 95.07, QED 0.43
Compound (SMILES): COc1ccc([C@H](C)NC(=O)COc2cc(C(F)F)c3c(-c4cc(C)oc4C)nn(C)c3n2)cc1
InChIKey: YIWTXIFCMFZIRO-AWEZNQCLSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 484.5, ALogP 5.05, HBA 7, HBD 1, PSA 91.41, QED 0.38
Compound (SMILES): Cc1ccc2c(c1)CCC2NC(=O)COc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: LADVEYKZADVBJM-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 908 nM (pChEMBL 6.039999961853027)
Descriptors: MW 390.49, ALogP 3.65, HBA 5, HBD 1, PSA 69.04, QED 0.72
Compound (SMILES): COc1ccc2c(c1)CC[C@@H]2NC(=O)COc1cc(C(F)F)c2c(C3CC3)nn(C)c2n1
InChIKey: XSUIGCPNDJKEIF-KRWDZBQOSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 442.47, ALogP 3.97, HBA 6, HBD 1, PSA 78.27, QED 0.6
Compound (SMILES): COc1ccc2c(c1)CC[C@@H]2NC(=O)COc1cc(C(F)(F)F)c2c(C3CC3)nn(C)c2n1
InChIKey: ZGUXBVWYPWYBCZ-KRWDZBQOSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 18 nM (pChEMBL 7.75)
Descriptors: MW 460.46, ALogP 4.06, HBA 6, HBD 1, PSA 78.27, QED 0.6
Compound (SMILES): Cc1ccc2c(c1)CC[C@@H]2NC(=O)COc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: LADVEYKZADVBJM-SFHVURJKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 390.49, ALogP 3.65, HBA 5, HBD 1, PSA 69.04, QED 0.72
Compound (SMILES): Cc1cc(OCC(=O)NC(C)c2cnc3[nH]ccc3c2)nc2c1c(C1CC1)nn2C
InChIKey: HLDWPRBQSIKKSV-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 358 nM (pChEMBL 6.449999809265137)
Descriptors: MW 404.47, ALogP 3.29, HBA 6, HBD 2, PSA 97.72, QED 0.51
Compound (SMILES): Cc1cc(OCC(=O)NC(C)c2ccc3c(ccn3C)c2)nc2c1c(C1CC1)nn2C
InChIKey: QBNVNLZYTSCLAT-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 162 nM (pChEMBL 6.789999961853027)
Descriptors: MW 417.51, ALogP 3.9, HBA 6, HBD 1, PSA 73.97, QED 0.52
Compound (SMILES): Cc1ccc2c(n1)CCC2NC(=O)COc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: FVNQXXWGMZMSAA-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 159 nM (pChEMBL 6.800000190734863)
Descriptors: MW 391.48, ALogP 3.04, HBA 6, HBD 1, PSA 81.93, QED 0.72
Compound (SMILES): CCOc1ccc2c(c1)CC[C@@H]2NC(=O)COc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: OJFITYODHBZMLE-IBGZPJMESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 317 nM (pChEMBL 6.5)
Descriptors: MW 420.51, ALogP 3.74, HBA 6, HBD 1, PSA 78.27, QED 0.63
Compound (SMILES): COc1ccc2c(c1)CC[C@@H]2NC(=O)C(C)Oc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: QXVOQEVRXUTGSY-PKDNWHCCSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 589 nM (pChEMBL 6.230000019073486)
Descriptors: MW 420.51, ALogP 3.73, HBA 6, HBD 1, PSA 78.27, QED 0.66
Compound (SMILES): C[C@H](NC(=O)COc1cc(C(F)(F)F)c2c(-c3ccccc3)cn(C)c2n1)c1ccccc1
InChIKey: RDHXDMAVHATBQH-INIZCTEOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay I : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 100 pM of the radioligand ([125l]orexin A, 2100 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 501 nM (pChEMBL 6.300000190734863)
Descriptors: MW 453.46, ALogP 5.52, HBA 4, HBD 1, PSA 56.15, QED 0.42
Compound (SMILES): Cc1ccc2c(n1)CC[C@@H]2NC(=O)COc1cc(C(F)(F)F)c2c(-c3cc(C)oc3C)nn(C)c2n1
InChIKey: OEOHGCWORFHBJS-IBGZPJMESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 499.49, ALogP 4.75, HBA 7, HBD 1, PSA 95.07, QED 0.43
Compound (SMILES): COc1cc2c(cc1OC)C(NC(=O)COc1cc(C)c3c(C4CC4)nn(C)c3n1)CC2
InChIKey: LLOHRTXINIAVCH-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 436.51, ALogP 3.35, HBA 7, HBD 1, PSA 87.5, QED 0.61
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C)c3c(C4CC4)nn(C)c3n2)cc1
InChIKey: FZXJNTCYSQYSIW-HNNXBMFYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 378.48, ALogP 3.72, HBA 5, HBD 1, PSA 69.04, QED 0.71
Compound (SMILES): COc1ccc2c(c1)CC[C@@H]2NC(=O)COc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: NHKDZRLVFDFWKF-SFHVURJKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 406.49, ALogP 3.35, HBA 6, HBD 1, PSA 78.27, QED 0.68
Compound (SMILES): COc1ccccc1-c1nn(C(C)(C)C)cc1CN1CCC2(CC1)CN(c1ccc(C(=O)O)cc1)C(=O)O2
InChIKey: GDSTXWMZVZSFEC-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Binding Assay: SSTR5 binding assays can be performed by labeling somatostatin and determining the ability of a compound to inhibit somatostatin binding. (Poitout et al., J. Med. Chem. 44:29900-3000, (2001); Hocart et al., J. Med. Chem. 41:1146-1154, (1998); J. Med. Chem. 50, 6292-6295 (2007) and J. Med. Chem. 50, 6295-6298 (2007)). Binding assays were performed using (3-125I-Tyr11)-SRIF-14 or (3-125I-Tyr11)-SRIF-28 as the radioligand (used at 0.1 nM) and The Packard Unifilter assay plate. The assay buffer consisted of 50 mM TrisHCl (pH 7.8) with 1 mM EGTA, 5 in M MgCl2, leupeptin (10 μg/mL), pepstatin (10 μg/mL), bacitracin (200 μg/mL), and aprotinin (0.5 μg/mL).
Measurement: IC50 = 1.804 nM (pChEMBL 8.739999771118164)
Descriptors: MW 518.61, ALogP 5, HBA 7, HBD 1, PSA 97.13, QED 0.49
Compound (SMILES): CCOc1cc(CN2CCC3(CC2)CN(c2ccc(C(=O)O)cc2)C(=O)O3)cc(OCC)c1-c1ccc(F)cc1
InChIKey: KKHVNUWBIYHFEO-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Antagonist activity at human SSR5 expressed in CHOK1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin addition measured after 1 hr by LANCE assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 548.61, ALogP 5.98, HBA 6, HBD 1, PSA 88.54, QED 0.35
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4cc(O)c(C)cc4F)c3c2)ccc1O
InChIKey: MZDUBFXCVNFNTD-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 301.1 nM (pChEMBL 6.519999980926514)
Descriptors: MW 391.4, ALogP 4.91, HBA 6, HBD 3, PSA 87.5, QED 0.46