lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(c1cc2ncc(Br)cn2n1)N1CCc2ccc(Cl)nc2CC1
InChIKey: OPKPLRYJWROWIB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 146 nM (pChEMBL 6.840000152587891)
Descriptors: MW 406.67, ALogP 2.78, HBA 5, HBD 0, PSA 63.39, QED 0.58
Compound (SMILES): COc1ccc2c(n1)CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2
InChIKey: OSJCMUZODXPDSL-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 402.25, ALogP 2.14, HBA 6, HBD 0, PSA 72.62, QED 0.66
Compound (SMILES): O=C(c1cc2ncc(Br)cn2n1)N1CCc2ccsc2CC1
InChIKey: OHYAXRDMSLZLIC-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 1385 nM (pChEMBL 5.860000133514404)
Descriptors: MW 377.27, ALogP 2.79, HBA 5, HBD 0, PSA 50.5, QED 0.66
Compound (SMILES): CCc1nc2c(s1)CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2
InChIKey: OEYKQCOFIDDHKA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 406.31, ALogP 2.75, HBA 6, HBD 0, PSA 63.39, QED 0.66
Compound (SMILES): O=C(c1cc2ncc(Br)cn2n1)N1CCc2ncsc2CC1
InChIKey: HFBSTQOCRHPHJB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 378.26, ALogP 2.19, HBA 6, HBD 0, PSA 63.39, QED 0.65
Compound (SMILES): Cc1nc2c(s1)CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2
InChIKey: PPBYGUATKIHBBC-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 392.28, ALogP 2.5, HBA 6, HBD 0, PSA 63.39, QED 0.64
Compound (SMILES): O=C(c1cc2ncc(Br)cn2n1)N1CCc2cc(Cl)nnc2CC1
InChIKey: CXOBWJUAOFASQO-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 407.66, ALogP 2.18, HBA 6, HBD 0, PSA 76.28, QED 0.62
Compound (SMILES): COCc1nc2c(s1)CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2
InChIKey: BRYPHYOGDVFMNH-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 1545 nM (pChEMBL 5.809999942779541)
Descriptors: MW 422.31, ALogP 2.34, HBA 7, HBD 0, PSA 72.62, QED 0.65
Compound (SMILES): Cc1cnc2cc(C(=O)N3CCc4ncsc4CC3)nn2c1
InChIKey: HQMDCMIPCJVWRJ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 1420 nM (pChEMBL 5.849999904632568)
Descriptors: MW 313.39, ALogP 1.74, HBA 6, HBD 0, PSA 63.39, QED 0.69
Compound (SMILES): O=C(c1cc2ncc(Cl)cn2n1)N1CCc2ncsc2CC1
InChIKey: UNBIVDPTRGTTPR-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 333.8, ALogP 2.08, HBA 6, HBD 0, PSA 63.39, QED 0.68
Compound (SMILES): O=C(c1cc2ncc(Br)cn2n1)N1CCc2[nH]c(=O)sc2CC1
InChIKey: NFUGEPSHTBCNFR-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 394.25, ALogP 1.48, HBA 6, HBD 1, PSA 83.36, QED 0.68
Compound (SMILES): CC(C)c1nc2c(s1)CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2
InChIKey: DINILBUSTAPYDB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 148 nM (pChEMBL 6.829999923706055)
Descriptors: MW 420.34, ALogP 3.31, HBA 6, HBD 0, PSA 63.39, QED 0.64
Compound (SMILES): Cc1nc2c(s1)CCN(C(=O)c1cc3ncc(Cl)cn3n1)CC2
InChIKey: WOOXFLPCMNOANB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 347.83, ALogP 2.39, HBA 6, HBD 0, PSA 63.39, QED 0.68
Compound (SMILES): O=C(c1cc2ncc(Br)cn2n1)N1CCc2cccnc2CC1
InChIKey: TZWRDBPOCJQISB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 603 nM (pChEMBL 6.21999979019165)
Descriptors: MW 372.23, ALogP 2.13, HBA 5, HBD 0, PSA 63.39, QED 0.66
Compound (SMILES): Cn1cnc2c1CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2
InChIKey: HTTCOCDHRFMKBF-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 692 nM (pChEMBL 6.159999847412109)
Descriptors: MW 375.23, ALogP 1.47, HBA 6, HBD 0, PSA 68.32, QED 0.65
Compound (SMILES): Cn1c2c(sc1=O)CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2
InChIKey: OGZNOTUYMHUJHG-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 1285 nM (pChEMBL 5.889999866485596)
Descriptors: MW 408.28, ALogP 1.49, HBA 7, HBD 0, PSA 72.5, QED 0.61
Compound (SMILES): Cn1c2c(c3ccccc31)CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2
InChIKey: BNGHHQQJYFBBEC-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 424.3, ALogP 3.22, HBA 5, HBD 0, PSA 55.43, QED 0.47
Compound (SMILES): CC(C)c1nc2c(s1)CCN(C(=O)c1cc3ncc(Cl)cn3n1)CC2
InChIKey: SLJUBBDNWOFUGZ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 375.88, ALogP 3.2, HBA 6, HBD 0, PSA 63.39, QED 0.69
Compound (SMILES): O=C(c1cc2ncc(Cl)cn2n1)N1CCc2[nH]c(=O)sc2CC1
InChIKey: PHTXEXDUGBXUIJ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: FLIPR Assay: Activation of the mGluR5 receptor expressed in cell lines results in an increase in intracellular calcium concentration. Using calcium sensitive fluorescent dyes and a suited fluorescence plate reader this functional response is detectable and quantifiable. This technique could be used to characterize pharmacological modifications of the mGluR5 receptor.[Ca]i measurements were performed in HEK293 cells stably expressing the full-length human mGlu5a receptor under the control of a tet-regulated promoter. Cells were cultivated in Dulbecco's modified eagle's medium (DMEM) with 10% fetal calf serum, 100 ug/ml HygromycinB, 500 ug/ml G418 and 2 ug/ml Tetracycline in a 37, 95% humidity and 5% CO2 incubator. Confluent cell cultures were split on a bi-weekly schedule.72 hours prior to the assay run mGluR5a expression was induced by replacing the culture medium by DMEM with 10% fetal calf serum without antibiotics.
Measurement: IC50 = 128 nM (pChEMBL 6.889999866485596)
Descriptors: MW 349.8, ALogP 1.37, HBA 6, HBD 1, PSA 83.36, QED 0.72
Compound (SMILES): CN1C(=N)N[C@](C)(c2cc(NC(=O)c3ccc(Cl)cn3)ccc2F)CS1(=O)=O
InChIKey: VBWPFVMZZPWFMD-KRWDZBQOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE1 using biotin-GLTNIKTEEISEISYEVEFR-C[Oregon green]KK-OH as substrate after 3 hrs by fluorescence polarization assay
Measurement: IC50 < 2.2 nM (pChEMBL 8.657999992370605)
Descriptors: MW 425.87, ALogP 2.14, HBA 5, HBD 3, PSA 115.25, QED 0.7
Compound (SMILES): CN1C(=N)N[C@](C)(c2cc(NC(=O)c3ccc(C(F)(F)F)cn3)ccc2F)CS1(=O)=O
InChIKey: XBJQDMHXDUQMJV-KRWDZBQOSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: HTRF FRET Assay: Inhibitor IC50s at purified human autoBACE-2 were determined in a time-resolved endpoint proteolysis assay that measures hydrolysis of the QSY7-EISEVNLDAEFC-Eu-amide FRET peptide substrate (BACE-HTRF assay). BACE-mediated hydrolysis of this peptide results in an increase in relative fluorescence (RFU) at 620 nm after excitation with 320 nm light. Inhibitor compounds, prepared at 3x the desired final concentration in 1xBACE assay buffer (20 mM sodium acetate pH 5.0, 10% glycerol, 0.1% Brij-35) supplemented with 7.5% DMSO were pre-incubated with an equal volume of autoBACE-2 enzyme diluted in 1xBACE assay buffer (final enzyme concentration 1 nM) in black 384-well NUNC plates for 30 minutes at 30 C. The assay was initiated by addition of an equal volume of the QSY7-EISEVNLDAEFC-Eu-amide substrate (200 nM final concentration, Km=8 M for 4 M for autoBACE-2) prepared in 1xBACE assay buffer supplemented with 7.5% DMSO and incubated for 90 minutes at 30 C.
Measurement: Ki = 2.46 nM (pChEMBL 8.609999656677246)
Descriptors: MW 459.43, ALogP 2.51, HBA 5, HBD 3, PSA 115.25, QED 0.61
Compound (SMILES): Cc1cnc(C(=O)Nc2ccc(F)c([C@]3(C)CS(=O)(=O)N(C)C(=N)N3)c2)cn1
InChIKey: QEDBRPQZTWTMTK-KRWDZBQOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: HTRF FRET Assay: A homogeneous time-resolved FRET assay was used to determine IC50 values for inhibitors of the soluble human BACE1 catalytic domain. This assay monitored the increase of 620 nm fluorescence that resulted from BACE1 cleavage of an APPswedish APPswe mutant peptide FRET substrate (QSY7-EISEVNLDAEFC-Europium-amide). This substrate contained an N-terminal QSY7 moiety that served as a quencher of the C-terminal Europium fluorophore (620 nm Em). In the absence of enzyme activity, 620 nm fluorescence was low in the assay and increased linearly over 3 hours in the presence of uninhibited BACE1 enzyme. Inhibition of BACE1 cleavage of the QSY7-APPswe-Eu substrate by inhibitors was manifested as a suppression of 620 nm fluorescence.Varying concentrations of inhibitors at 3x the final desired concentration in a volume of 10 ul were preincubated with purified human BACE1 catalytic domain (3 nM in 10 ul) for 30 minutes at 30 C. in reaction buffer containing 20 mM Na-Acetate pH 5.0.
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 406.44, ALogP 1.19, HBA 6, HBD 3, PSA 128.14, QED 0.7
Compound (SMILES): COc1cnc(C(=O)Nc2cc(F)c(F)c([C@]3(C)CS(=O)(=O)N(C)C(=N)N3)c2)cn1
InChIKey: QGPBROSNFKNVFL-KRWDZBQOSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: HTRF assay: Inhibitor IC50s at purified human autoBACE-2 were determined in a time-resolved endpoint proteolysis assay that measures hydrolysis of the QSY7-EISEVNLDAEFC-Eu-amide FRET peptide substrate (BACE-HTRF assay). BACE-mediated hydrolysis of this peptide results in an increase in relative fluorescence (RFU) at 620 nm after excitation with 320 nm light. Inhibitor compounds, prepared at 3x the desired final concentration in 1xBACE assay buffer (20 mM sodium acetate pH 5.0, 10% glycerol, 0.1% Brij-35) supplemented with 7.5% DMSO were pre-incubated with an equal volume of autoBACE-2 enzyme diluted in 1xBACE assay buffer (final enzyme concentration 1 nM) in black 384-well NUNC plates for 30 minutes at 30 C. The assay was initiated by addition of an equal volume of the QSY7-EISEVNLDAEFC-Eu-amide substrate (200 nM final concentration, Km=8 uM for 4 uM for autoBACE-2) prepared in 1xBACE assay buffer supplemented with 7.5% DMSO and incubated for 90 minutes at 30 C.
Measurement: Ki = 2.15 nM (pChEMBL 8.670000076293945)
Descriptors: MW 440.43, ALogP 1.03, HBA 7, HBD 3, PSA 137.37, QED 0.65
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(F)c([C@]3(C)CS(=O)(=O)N(C)C(=N)N3)c2)nc1
InChIKey: LWWIOJQKELULTO-SFHVURJKSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: HTRF FRET Assay: Inhibitor IC50s at purified human autoBACE-2 were determined in a time-resolved endpoint proteolysis assay that measures hydrolysis of the QSY7-EISEVNLDAEFC-Eu-amide FRET peptide substrate (BACE-HTRF assay). BACE-mediated hydrolysis of this peptide results in an increase in relative fluorescence (RFU) at 620 nm after excitation with 320 nm light. Inhibitor compounds, prepared at 3x the desired final concentration in 1xBACE assay buffer (20 mM sodium acetate pH 5.0, 10% glycerol, 0.1% Brij-35) supplemented with 7.5% DMSO were pre-incubated with an equal volume of autoBACE-2 enzyme diluted in 1xBACE assay buffer (final enzyme concentration 1 nM) in black 384-well NUNC plates for 30 minutes at 30 C. The assay was initiated by addition of an equal volume of the QSY7-EISEVNLDAEFC-Eu-amide substrate (200 nM final concentration, Km=8 M for 4 M for autoBACE-2) prepared in 1xBACE assay buffer supplemented with 7.5% DMSO and incubated for 90 minutes at 30 C.
Measurement: Ki = 0.45 nM (pChEMBL 9.350000381469727)
Descriptors: MW 405.46, ALogP 1.8, HBA 5, HBD 3, PSA 115.25, QED 0.72
Compound (SMILES): CN1C(=N)N[C@](C)(c2cc(-c3cccc(C#N)c3)cs2)CS1(=O)=O
InChIKey: WRIHQAVUMDUZBP-INIZCTEOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: BACE1 HTRF FRET Assay: This assay monitored the increase of 620 nm fluorescence that resulted from BACE1 cleavage of an APPswedish APPswe mutant peptide FRET substrate (QSY7-EISEVNLDAEFC-Europium-amide). This substrate contained an N-terminal QSY7 moiety that served as a quencher of the C-terminal Europium fluorophore (620 nm Em). In the absence of enzyme activity, 620 nm fluorescence was low in the assay and increased linearly over 3 hours in the presence of uninhibited BACE1 enzyme. Inhibition of BACE1 cleavage of the QSY7-APPswe-Eu substrate by inhibitors was manifested as a suppression of 620 nm fluorescence. Varying concentrations of inhibitors at 3× the final desired concentration in a volume of 10 ul were preincubated with purified human BACE1 catalytic domain (3 nM in 10 Ml) for 30 minutes at 30° C. in reaction buffer containing 20 mM Na-Acetate pH 5.0, 10% glycerol, 0.1% Brij-35 and 7.5% DSMO. Reactions were initiated by addition of 10 μl of 600 nM QSY7-APPswe-Eu substrate (200 nM final) to give a final reaction volume of 30 μl in a 384 well Nunc HTRF plate. The reactions were incubated at 30° C. for 1.5 hours. The 620 nm fluorescence was then read on a Rubystar HTRF plate reader (BMG Labtechnologies) using a 50 μs delay followed by a 400 millisecond acquisition time window. Inhibitor IC50 values were derived from non-linear regression analysis of concentration response curves. Ki values were then calculated from IC50 values using the Cheng-Prusoff equation using a previously determined m value of 8 μM for the QSY7-APPswe-Eu substrate at BACE1.
Measurement: Ki = 25600 nM (pChEMBL 4.590000152587891)
Descriptors: MW 360.46, ALogP 2.3, HBA 5, HBD 2, PSA 97.05, QED 0.86
Compound (SMILES): CN1C(=N)N[C@](C)(c2cc(-c3ccc(F)c(C#N)c3)cs2)CS1(=O)=O
InChIKey: BRXXBTMKBTXEJJ-INIZCTEOSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: HTRF assay: Inhibitor IC50s at purified human autoBACE-2 were determined in a time-resolved endpoint proteolysis assay that measures hydrolysis of the QSY7-EISEVNLDAEFC-Eu-amide FRET peptide substrate (BACE-HTRF assay). BACE-mediated hydrolysis of this peptide results in an increase in relative fluorescence (RFU) at 620 nm after excitation with 320 nm light. Inhibitor compounds, prepared at 3x the desired final concentration in 1xBACE assay buffer (20 mM sodium acetate pH 5.0, 10% glycerol, 0.1% Brij-35) supplemented with 7.5% DMSO were pre-incubated with an equal volume of autoBACE-2 enzyme diluted in 1xBACE assay buffer (final enzyme concentration 1 nM) in black 384-well NUNC plates for 30 minutes at 30 C. The assay was initiated by addition of an equal volume of the QSY7-EISEVNLDAEFC-Eu-amide substrate (200 nM final concentration, Km=8 uM for 4 uM for autoBACE-2) prepared in 1xBACE assay buffer supplemented with 7.5% DMSO and incubated for 90 minutes at 30 C.
Measurement: Ki = 8.23 nM (pChEMBL 8.09000015258789)
Descriptors: MW 378.45, ALogP 2.44, HBA 5, HBD 2, PSA 97.05, QED 0.84
Compound (SMILES): COc1cnc(C(=O)Nc2ccc(F)c([C@]3(C)CS(=O)(=O)N(C)C(=N)N3)c2)cn1
InChIKey: DJIXTIKKTNRBEW-KRWDZBQOSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: HTRF FRET Assay: Inhibitor IC50s at purified human autoBACE-2 were determined in a time-resolved endpoint proteolysis assay that measures hydrolysis of the QSY7-EISEVNLDAEFC-Eu-amide FRET peptide substrate (BACE-HTRF assay). BACE-mediated hydrolysis of this peptide results in an increase in relative fluorescence (RFU) at 620 nm after excitation with 320 nm light. Inhibitor compounds, prepared at 3x the desired final concentration in 1xBACE assay buffer (20 mM sodium acetate pH 5.0, 10% glycerol, 0.1% Brij-35) supplemented with 7.5% DMSO were pre-incubated with an equal volume of autoBACE-2 enzyme diluted in 1xBACE assay buffer (final enzyme concentration 1 nM) in black 384-well NUNC plates for 30 minutes at 30 C. The assay was initiated by addition of an equal volume of the QSY7-EISEVNLDAEFC-Eu-amide substrate (200 nM final concentration, Km=8 M for 4 M for autoBACE-2) prepared in 1xBACE assay buffer supplemented with 7.5% DMSO and incubated for 90 minutes at 30 C.
Measurement: Ki = 1.99 nM (pChEMBL 8.699999809265137)
Descriptors: MW 422.44, ALogP 0.89, HBA 7, HBD 3, PSA 137.37, QED 0.67
Compound (SMILES): C[C@@H]1C[S+]([O-])[C@@H](COc2ccc(F)cn2)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: WPZDYCILLWZIQO-RLGHVENUSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 429.48, ALogP 1.84, HBA 7, HBD 0, PSA 96.2, QED 0.57
Compound (SMILES): C[C@@H]1CS(=O)(=O)[C@@H](COc2ccc(F)cn2)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: GYBUTWSMPPPWKR-GDBMZVCRSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 445.48, ALogP 1.51, HBA 8, HBD 0, PSA 107.28, QED 0.59
Compound (SMILES): C[C@@H]1CS[C@@H](CSc2ccccn2)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: FPJPOFCHXDDGEK-HZPDHXFCSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 411.56, ALogP 3.4, HBA 7, HBD 0, PSA 63.91, QED 0.6
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2C[C@H](COc3ccc(F)cn3)SC[C@H]2C)c1
InChIKey: PYKRMGBCBZXQMO-NVXWUHKLSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 0.38 nM (pChEMBL 9.420000076293945)
Descriptors: MW 427.51, ALogP 3.13, HBA 7, HBD 0, PSA 73.14, QED 0.62
Compound (SMILES): Cc1ccc(OC[C@H]2CN(C(=O)c3ccccc3-n3nccn3)[C@H](C)CS2)nc1
InChIKey: MHLHIWUERGBCJP-IAGOWNOFSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 409.52, ALogP 3, HBA 7, HBD 0, PSA 73.14, QED 0.65
Compound (SMILES): C[C@@H]1CS[C@@H](COc2ccc(Cl)cn2)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: HKXBHSSMEQTLRR-GDBMZVCRSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 429.93, ALogP 3.34, HBA 7, HBD 0, PSA 73.14, QED 0.62
Compound (SMILES): C[C@@H]1CS[C@@H](COc2ccc(C(F)(F)F)cn2)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: BNYGTIRYWBTFQO-GDBMZVCRSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 463.49, ALogP 3.71, HBA 7, HBD 0, PSA 73.14, QED 0.57
Compound (SMILES): C[C@@H]1CS[C@@H](COc2ncccc2Cl)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: YIIVBAKIMWUVOU-HUUCEWRRSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 75.7 nM (pChEMBL 7.119999885559082)
Descriptors: MW 429.93, ALogP 3.34, HBA 7, HBD 0, PSA 73.14, QED 0.62
Compound (SMILES): Cc1ccnc(OC[C@H]2CN(C(=O)c3ccccc3-n3nccn3)[C@H](C)CS2)c1
InChIKey: XGMFQOMEOGFKBD-IAGOWNOFSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 192 nM (pChEMBL 6.71999979019165)
Descriptors: MW 409.52, ALogP 3, HBA 7, HBD 0, PSA 73.14, QED 0.65
Compound (SMILES): Cc1nc(OC[C@H]2CN(C(=O)c3ccccc3-n3nccn3)[C@H](C)CS2)ncc1Cl
InChIKey: CIKWFXRTJZPTKO-UKRRQHHQSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 32 nM (pChEMBL 7.5)
Descriptors: MW 444.95, ALogP 3.04, HBA 8, HBD 0, PSA 86.03, QED 0.6
Compound (SMILES): Cc1cnc(OC[C@H]2CN(C(=O)c3ccccc3-n3nccn3)[C@H](C)CS2)nc1Cl
InChIKey: CUQIZMJRMJJSEL-HUUCEWRRSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: FLIPR Ca2+ Flux Assay: The utility of the compounds in accordance with the present invention as orexin receptor OX1R and/or OX2R antagonists may be readily determined without undue experimentation by methodology well known in the art, including the FLIPR Ca2+ Flux Assay (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001). In a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine.
Measurement: Ki = 1119 nM (pChEMBL 5.949999809265137)
Descriptors: MW 444.95, ALogP 3.04, HBA 8, HBD 0, PSA 86.03, QED 0.56