lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#Cc1c(Oc2ccc(F)c(NC(=O)Cc3cccc(C(F)(F)F)c3)c2)ccc2nc(NC(=O)C3CC3)sc12
InChIKey: OJFKUJDRGJSAQB-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of CRAF (unknown origin) compound preincubated for 1 hr in presence of 1000 uM ATP
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 554.53, ALogP 6.65, HBA 6, HBD 2, PSA 104.11, QED 0.25
Compound (SMILES): CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3ccc4nc(NC(=O)C5CC5)sc4c3C#N)c2)c1
InChIKey: SCBRZJLDCOOJMH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of N-terminal FLAG-tagged recombinant BRAF V600E mutant (unknown origin) expressed in baculovirus system preincubated for 10 mins before substrate addition measured after 20 mins by scintillation counting
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 521.6, ALogP 6.36, HBA 7, HBD 2, PSA 127.9, QED 0.29
Compound (SMILES): CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3ccc4nc(NC(=O)C5CC5)sc4c3[N+](=O)[O-])c2)c1
InChIKey: BZNZGSHCDPQKRW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of N-terminal FLAG-tagged recombinant BRAF V600E mutant (unknown origin) expressed in baculovirus system preincubated for 10 mins before substrate addition measured after 20 mins by scintillation counting
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 541.59, ALogP 6.4, HBA 8, HBD 2, PSA 147.25, QED 0.19
Compound (SMILES): COC(=O)c1c(Oc2cccc(NC(=O)c3cccc(C(C)(C)C#N)c3)c2)ccc2nc(NC(=O)C3CC3)sc12
InChIKey: UVLIORXAVFYPED-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of N-terminal FLAG-tagged recombinant BRAF V600E mutant (unknown origin) expressed in baculovirus system preincubated for 10 mins before substrate addition measured after 20 mins by scintillation counting
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 554.63, ALogP 6.28, HBA 8, HBD 2, PSA 130.41, QED 0.25
Compound (SMILES): O=C(NCc1ccc(F)c(Cl)c1)c1c(O)c2cccnc2n(O)c1=O
InChIKey: ZMWNOXHZOQBNOQ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV-1 integrase strand transfer activity
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 363.73, ALogP 2.06, HBA 6, HBD 3, PSA 104.45, QED 0.62
Compound (SMILES): O=C(NCc1ccc(F)c(F)c1)c1c(O)c2cccnc2n(O)c1=O
InChIKey: FWUVZSSWSPORBO-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV-1 integrase strand transfer activity
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 347.28, ALogP 1.55, HBA 6, HBD 3, PSA 104.45, QED 0.62
Compound (SMILES): O=C(NCc1ccc(F)cc1F)c1c(O)c2cccnc2n(O)c1=O
InChIKey: OJGJNBQMUGMKTG-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV-1 integrase strand transfer activity
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 347.28, ALogP 1.55, HBA 6, HBD 3, PSA 104.45, QED 0.62
Compound (SMILES): O=C(NCc1ccc(F)cc1F)c1cc2cccc(O)c2n(O)c1=O
InChIKey: FYXNVPHVFOQGSO-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV-1 integrase strand transfer activity
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 346.29, ALogP 2.15, HBA 5, HBD 3, PSA 91.56, QED 0.63
Compound (SMILES): O=C(NCc1ccc(F)c(Cl)c1)c1cc2cccnc2n(O)c1=O
InChIKey: AGNMEEDGMFYGNI-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV-1 integrase strand transfer activity
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 347.73, ALogP 2.36, HBA 5, HBD 2, PSA 84.22, QED 0.71
Compound (SMILES): O=C(NCc1ccc(F)c(F)c1)c1cc2cccnc2n(O)c1=O
InChIKey: MGMJKJHYVGBQKH-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV-1 integrase strand transfer activity
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 331.28, ALogP 1.84, HBA 5, HBD 2, PSA 84.22, QED 0.72
Compound (SMILES): O=C(NCc1ccc(F)cc1F)c1cc2cccnc2n(O)c1=O
InChIKey: VLKPQQHJINFIPV-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV-1 integrase strand transfer activity
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 331.28, ALogP 1.84, HBA 5, HBD 2, PSA 84.22, QED 0.72
Compound (SMILES): CCCN(CCN1CCN(c2ccc(-c3cccc(OC)c3)cc2)CC1)[C@H]1CCc2nc(N)sc2C1
InChIKey: DUVNCSZVWYCEFO-VWLOTQADSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19020
Assay: Displacement of [3H]spiroperidol from rat dopamine D3 receptor expressed in HEK293 cells
Measurement: Ki = 2.33 nM (pChEMBL 8.630000114440918)
Descriptors: MW 505.73, ALogP 4.79, HBA 7, HBD 1, PSA 57.86, QED 0.45
Compound (SMILES): CCCN(CCN1CCN(c2ccc(-c3cccc(O)c3)cc2)CC1)[C@H]1CCc2nc(N)sc2C1
InChIKey: VITUDJAVASFPKN-DEOSSOPVSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19020
Assay: Displacement of [3H]spiroperidol from rat dopamine D3 receptor expressed in HEK293 cells
Measurement: Ki = 1.73 nM (pChEMBL 8.760000228881836)
Descriptors: MW 491.71, ALogP 4.49, HBA 7, HBD 2, PSA 68.86, QED 0.48
Compound (SMILES): N#Cc1ccc(OCCCN2CCC(C(N)(c3ccccc3)C3CCCC3)CC2)cc1
InChIKey: AUWUGRCKTQSGJY-UHFFFAOYSA-N
Target: Menin (SINGLE PROTEIN), Homo sapiens
UniProt: O00255
Assay: Inhibition of FAM-probe binding to Menin (unknown origin) after 60 mins by fluorescence polarization competitive binding assay
Measurement: Ki = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 417.6, ALogP 5.08, HBA 4, HBD 1, PSA 62.28, QED 0.61
Compound (SMILES): Cc1cc2c(NC(=O)C(=O)O)cccc2n1Cc1ccc(O)c(C(C)C)c1
InChIKey: NUVOUOHXOKZTQW-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Displacement of [125I]-Triiodothyronine from human recombinant TRbeta1 ligand binding domain after 2 to 3 hrs by beta counting
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 366.42, ALogP 3.85, HBA 4, HBD 3, PSA 91.56, QED 0.61
Compound (SMILES): Cc1ccc(NC(=O)C(=O)O)c2ccn(Cc3ccc(O)c(C(C)C)c3)c12
InChIKey: QOWDVYZPDZEOEA-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Displacement of [125I]-Triiodothyronine from human recombinant TRbeta1 ligand binding domain after 2 to 3 hrs by beta counting
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 366.42, ALogP 3.85, HBA 4, HBD 3, PSA 91.56, QED 0.61
Compound (SMILES): CC(C)c1cc(Cn2ccc3c(NC(=O)C(=O)O)cccc32)ccc1O
InChIKey: AHPLOHJAEWIFEV-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Displacement of [125I]-Triiodothyronine from human recombinant TRbeta1 ligand binding domain after 2 to 3 hrs by beta counting
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 352.39, ALogP 3.54, HBA 4, HBD 3, PSA 91.56, QED 0.63
Compound (SMILES): Cc1cc2c(NC(=O)CC(=O)O)cccc2n1Cc1ccc(O)c(C(C)C)c1
InChIKey: RANBHGYNNSPWIV-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Displacement of [125I]-Triiodothyronine from human recombinant TRbeta1 ligand binding domain after 2 to 3 hrs by beta counting
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 380.44, ALogP 4.24, HBA 4, HBD 3, PSA 91.56, QED 0.56
Compound (SMILES): Cc1ccc(NC(=O)CC(=O)O)c2ccn(Cc3ccc(O)c(C(C)C)c3)c12
InChIKey: XSZSWHNJVRGLOK-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Displacement of [125I]-Triiodothyronine from human recombinant TRbeta1 ligand binding domain after 2 to 3 hrs by beta counting
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 380.44, ALogP 4.24, HBA 4, HBD 3, PSA 91.56, QED 0.56
Compound (SMILES): Cc1c(CCC(=O)O)c2ccccc2n1Cc1ccc(O)c(C(C)C)c1
InChIKey: UCFNGFLMPGVJJA-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Displacement of [125I]-Triiodothyronine from human recombinant TRbeta1 ligand binding domain after 2 to 3 hrs by beta counting
Measurement: IC50 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 351.45, ALogP 4.84, HBA 3, HBD 2, PSA 62.46, QED 0.67
Compound (SMILES): Cc1c(CCCC(=O)O)c2ccccc2n1Cc1ccc(O)c(C(C)C)c1
InChIKey: PYFRUYFQSHPGDE-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Displacement of [125I]-Triiodothyronine from human recombinant TRbeta1 ligand binding domain after 2 to 3 hrs by beta counting
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 365.47, ALogP 5.23, HBA 3, HBD 2, PSA 62.46, QED 0.6
Compound (SMILES): Cc1c(CCCCC(=O)O)c2ccccc2n1Cc1ccc(O)c(C(C)C)c1
InChIKey: KYMRCMVDQPTGCO-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Displacement of [125I]-Triiodothyronine from human recombinant TRbeta1 ligand binding domain after 2 to 3 hrs by beta counting
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 379.5, ALogP 5.62, HBA 3, HBD 2, PSA 62.46, QED 0.5
Compound (SMILES): CC(=O)O.CS(=O)(=O)c1ccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)cc1
InChIKey: DWZWKIJGNMJFHV-SNYZSRNZSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoceptor transfected in CHO cells assessed as cyclic AMP accumulation after 45 mins by fluorescence polarization assay
Measurement: EC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 493.67, ALogP 3.51, HBA 7, HBD 4, PSA 116.09, QED 0.25
Compound (SMILES): CC(=O)O.O=S(=O)(c1cccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)c1)C1CCCC1
InChIKey: VVUGQHSQCFTHGT-CZCBIWLKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in Escherichia coli using 7-benzyloxyquinoline as substrate
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 547.76, ALogP 4.82, HBA 7, HBD 4, PSA 116.09, QED 0.2
Compound (SMILES): CC(=O)O.Cc1cc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)cc(S(=O)(=O)C2CCCC2)c1
InChIKey: UKZFUCLKGYORJG-YNMZEGNTSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoceptor transfected in CHO cells assessed as cyclic AMP accumulation after 45 mins by fluorescence polarization assay
Measurement: EC50 = 0.5012 nM (pChEMBL 9.300000190734863)
Descriptors: MW 561.79, ALogP 5.13, HBA 7, HBD 4, PSA 116.09, QED 0.19
Compound (SMILES): CC(=O)O.O=S(=O)(c1ccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)cc1)C1CCCC1
InChIKey: DQXJQKYCHCEZCV-CZCBIWLKSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoceptor transfected in CHO cells assessed as cyclic AMP accumulation after 45 mins by fluorescence polarization assay
Measurement: EC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 547.76, ALogP 4.82, HBA 7, HBD 4, PSA 116.09, QED 0.2
Compound (SMILES): CC(=O)O.O=S(=O)(c1cccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)c1)C1CCCCC1
InChIKey: XGUUVCHIJQZJQA-YNMZEGNTSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoceptor transfected in CHO cells assessed as cyclic AMP accumulation after 45 mins by fluorescence polarization assay
Measurement: EC50 = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 561.79, ALogP 5.21, HBA 7, HBD 4, PSA 116.09, QED 0.18
Compound (SMILES): CC(=O)O.O=S(=O)(c1cccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)c1)C1CC=CC1
InChIKey: QJLFVHRIPWPVGX-CZCBIWLKSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoceptor transfected in CHO cells assessed as cyclic AMP accumulation after 45 mins by fluorescence polarization assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 545.74, ALogP 4.6, HBA 7, HBD 4, PSA 116.09, QED 0.16
Compound (SMILES): CC(=O)O.O=S1(=O)CCc2ccc(CCCCOCCCCCCNC[C@H](O)c3ccc(O)c(CO)c3)cc21
InChIKey: ZWYFOZRMWRZXRX-SNYZSRNZSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoceptor transfected in CHO cells assessed as cyclic AMP accumulation after 45 mins by fluorescence polarization assay
Measurement: EC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 505.68, ALogP 3.44, HBA 7, HBD 4, PSA 116.09, QED 0.26
Compound (SMILES): O=CO.O=S1(=O)CCCc2ccc(CCCCOCCCCCCNC[C@H](O)c3ccc(O)c(CO)c3)cc21
InChIKey: UCSRCNDVOKNFMP-YCBFMBTMSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoceptor transfected in CHO cells assessed as cyclic AMP accumulation after 45 mins by fluorescence polarization assay
Measurement: EC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 519.7, ALogP 3.83, HBA 7, HBD 4, PSA 116.09, QED 0.25
Compound (SMILES): CCCCCCCCCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)CCl)C(C)C
InChIKey: NHBJTTGFHCHQHS-VZTVMPNDSA-N
Target: Proprotein convertase subtilisin/kexin type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29122
Assay: Inhibition of recombinant C-terminal truncated human SPC4 expressed in drosophila Schneider 2 cells after 1 hr by spectrofluorometry
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 744.43, ALogP 1.19, HBA 8, HBD 11, PSA 283.29, QED 0.02
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(N)=O)[C@@H](C)O
InChIKey: NOQKKGLLEPBIAP-CIFQRKFTSA-N
Target: Furin (SINGLE PROTEIN), Homo sapiens
UniProt: P09958
Assay: Inhibition of furin (unknown origin)
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 1268.55
Compound (SMILES): CN(C)CCCN1C(=O)c2ccc3c4ccc5c6c(ccc(c7ccc(c2c37)C1=O)c64)C(=O)N(CCCN(C)C)C5=O
InChIKey: ASCSVRAUWKNNCO-UHFFFAOYSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of Stat3 phosphorylation in human MDA-MB-468 cells by Western blotting analysis in normoxia condition
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 560.65, ALogP 4.83, HBA 6, HBD 0, PSA 81.24, QED 0.15
Compound (SMILES): CCc1cc(-c2noc(-c3cc(C)nc(C(CC)CC)c3)n2)cc(C)c1OC[C@@H](O)CNC(=O)CO
InChIKey: CHIUPZSZKBJIHD-QFIPXVFZSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: GTPγS Binding Assay: GTPγS binding assays are performed in 96 well microtiter plates (Nunc, 442587) in a final volume of 200 μl, using membrane preparations of CHO cells expressing recombinant human S1P1 receptor or human S1P3 receptor. Assay conditions are 20 mM HEPES (Fluka, 54461), 100 mM NaCl (Fluka, 71378), 5 mM MgCl2 (Fluka, 63064), 0.1% BSA (Calbiochem, 126609), 1 μM GDP (Sigma, G-7127), 2.5% DMSO (Fluka, 41644), 50 pM 35S-GTPγS (Amersham Biosciences, SJ1320). The pH is 7.4. Test compounds are dissolved and diluted in 100% DMSO and pre-incubated at room temperature for 30 min in 150 μl of the above assay buffer, in the absence of 35S-GTPγS. After addition of 50 μl of 35S-GTPγS, the assay is incubated for 1 h at rt. The assay is terminated by transfer of the reaction mixture to a Multiscreen plate (Millipore, MAHFC1H60) using a cell harvester from Packard Biosciences, and the plates are washed with ice-cold 10 mM Na2HPO4/NaH2PO4 (70%/30%), dried, sealed at the bottom and, after addition of 25 μl MicroScint20 (Packard Biosciences, order#6013621), sealed on the top. Membrane-bound 35S-GTP-γS is measured with a TopCount from Packard Biosciences.
Measurement: EC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 496.61, ALogP 3.73, HBA 8, HBD 3, PSA 130.6, QED 0.35
Compound (SMILES): Cc1cc(Nc2ccc(NC(=O)c3cccc(Nc4ccnc5ccccc45)c3)cc2)nc(N)n1
InChIKey: LYBFHWMXJBZNBI-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of human N-terminal 600 residues-deleted DNMT1 using poly(dI-dC) as substrate in presence of AdoMet
Measurement: IC50 = 4110 nM (pChEMBL 5.389999866485596)
Descriptors: MW 461.53, ALogP 5.65, HBA 7, HBD 4, PSA 117.85, QED 0.26
Compound (SMILES): Cc1cc(Nc2cccc(NC(=O)c3cccc(Nc4ccnc5ccccc45)c3)c2)nc(N)n1
InChIKey: GRGNBXUBKBUEDX-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63009
Assay: Inhibition of rat recombinant PRMT1 using histone as substrate preincubated for 5 mins followed by substrate addition measured after 6.5 mins by liquid scintillation counting analysis in presence of [methyl-3H]-AdoMet
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 461.53, ALogP 5.65, HBA 7, HBD 4, PSA 117.85, QED 0.26
Compound (SMILES): O=C(Nc1ccc(Nc2ccnc3ccccc23)cc1)c1ccc(Nc2ccnc3ccccc23)cc1
InChIKey: MIVZAUUBMZYYER-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of human N-terminal 600 residues-deleted DNMT1 using poly(dI-dC) as substrate in presence of AdoMet
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 481.56, ALogP 7.52, HBA 5, HBD 3, PSA 78.94, QED 0.23
Compound (SMILES): Cc1cc(Nc2ccc(NC(=O)c3ccc(Nc4cc(C)nc(N)n4)cc3)cc2)nc(N)n1
InChIKey: HQIGTSYWJONWMK-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of human N-terminal 600 residues-deleted DNMT1 using poly(dI-dC) as substrate in presence of AdoMet
Measurement: IC50 = 2230 nM (pChEMBL 5.650000095367432)
Descriptors: MW 441.5, ALogP 3.79, HBA 9, HBD 5, PSA 156.76, QED 0.3
Compound (SMILES): COc1ccc2c(c1)C1CC1(C(=O)N1C3CNCC1C3)Cn1c-2c(C2CCCCC2)c2ccc(C(=O)NS(=O)(=O)N(C)C)cc21
InChIKey: QQJQXOIBORDNRE-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes after 30 mins in presence of NADPH
Measurement: EC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 631.8, ALogP 3.96, HBA 7, HBD 2, PSA 112.98, QED 0.43
Compound (SMILES): [O-][S+](CCNCCCc1ccccc1)C(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: IICLPRRTXKMOAA-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from Sprague-Dawley rat brain SERT after 60 mins by liquid scintillation counting analysis
Measurement: Ki = 1280 nM (pChEMBL 5.889999866485596)
Descriptors: MW 413.53, ALogP 5.03, HBA 2, HBD 1, PSA 35.09, QED 0.37
Compound (SMILES): [O-][S+](CCNCCCc1ccccc1)C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
InChIKey: IKCIJMRWKOYSQT-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 446.44, ALogP 6.05, HBA 2, HBD 1, PSA 35.09, QED 0.3
Compound (SMILES): [O-][S+](CCNCCCc1ccccc1)C(c1ccc(Br)cc1)c1ccc(Br)cc1
InChIKey: DNZVFEURSMOPDR-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 7580 nM (pChEMBL 5.119999885559082)
Descriptors: MW 535.35, ALogP 6.27, HBA 2, HBD 1, PSA 35.09, QED 0.25
Compound (SMILES): O=C(CSC(c1ccc(Br)cc1)c1ccc(Br)cc1)NCCCc1ccccc1
InChIKey: UWSCLSVRYFYMEH-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 36300 nM (pChEMBL 4.440000057220459)
Descriptors: MW 533.33, ALogP 6.78, HBA 2, HBD 1, PSA 29.1, QED 0.31
Compound (SMILES): O=C(CSC(c1ccccc1)c1ccccc1)NCCCCc1ccccc1
InChIKey: GFRKAPPUDAFPTC-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 7980 nM (pChEMBL 5.099999904632568)
Descriptors: MW 389.56, ALogP 5.65, HBA 2, HBD 1, PSA 29.1, QED 0.45
Compound (SMILES): CNC(=O)C[S+]([O-])C(c1ccccc1)c1ccccc1
InChIKey: USDHVNQXFRZMAP-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 287.38, ALogP 2.27, HBA 2, HBD 1, PSA 52.16, QED 0.86
Compound (SMILES): NCCSC(c1ccc(Cl)cc1)c1ccc(Cl)cc1
InChIKey: UZCXWMDBXCJWSY-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Binding affinity to human DAT A480T mutant expressed in African green monkey COS7 cells assessed as inhibition of [3H]-dopamine uptake after 5 mins by beta-scintillation counting analysis
Measurement: Ki = 1370 nM (pChEMBL 5.860000133514404)
Descriptors: MW 312.26, ALogP 4.77, HBA 2, HBD 1, PSA 26.02, QED 0.86
Compound (SMILES): NCCSC(c1ccc(Br)cc1)c1ccc(Br)cc1
InChIKey: BATSWGXPUVZTJQ-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 8580 nM (pChEMBL 5.070000171661377)
Descriptors: MW 401.17, ALogP 4.99, HBA 2, HBD 1, PSA 26.02, QED 0.76
Compound (SMILES): c1ccc(C(SCCNCC2CC2)c2ccccc2)cc1
InChIKey: YJPRBYFNOMICPU-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Norepinephrine Transporter Binding Assay. Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000×g for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.). Each compound was tested with concentrations ranging from 0.01 nM to 100 mM for competition against binding of [3H]Nisoxetine, in at least three independent experiments, each performed in triplicate. Data were analyzed by using GraphPad Prism software (San Diego, Calif.) [11; Zou et. al. J. Med. Chem. 2006, 49, 6391-6399]. The results of the in vitro assays, grouped by functionality into the amides and amines are presented in Tables 1 and 2, respectively. All compounds were tested as racemic mixtures.
Measurement: Ki = 17500 nM (pChEMBL 4.760000228881836)
Descriptors: MW 297.47, ALogP 4.51, HBA 2, HBD 1, PSA 12.03, QED 0.72
Compound (SMILES): CCCCNCCSC(c1ccccc1)c1ccccc1
InChIKey: OQYIBJBEMZBPHB-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 11500 nM (pChEMBL 4.940000057220459)
Descriptors: MW 299.48, ALogP 4.9, HBA 2, HBD 1, PSA 12.03, QED 0.66
Compound (SMILES): c1ccc(CCCNCCSC(c2ccccc2)c2ccccc2)cc1
InChIKey: RQIJEINZTIJVAW-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Serotonin Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, midbrain dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 15 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at room temperature. Each tube contained 1.4 nM [3H]Citalopram (Amersham Biosciences, Piscataway, N.J.) and 1.5 mg midbrain tissue (original wet weight). Nonspecific binding was determined using 10 mM fluoxetine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.3% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted the next day using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 853 nM (pChEMBL 6.070000171661377)
Descriptors: MW 361.55, ALogP 5.73, HBA 2, HBD 1, PSA 12.03, QED 0.46
Compound (SMILES): Fc1ccc(C(SCCNCCCc2ccccc2)c2ccc(F)cc2)cc1
InChIKey: IWZNOFWARONDLD-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human D2R expressed in HEK293 cell membranes incubated for 1 hr by radioligand binding assay
Measurement: Ki = 228 nM (pChEMBL 6.639999866485596)
Descriptors: MW 397.53, ALogP 6.01, HBA 2, HBD 1, PSA 12.03, QED 0.42
Compound (SMILES): Brc1ccc(C(SCCNCCCc2ccccc2)c2ccc(Br)cc2)cc1
InChIKey: OQRQLSXKDJYXQN-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 3180 nM (pChEMBL 5.5)
Descriptors: MW 519.35, ALogP 7.26, HBA 2, HBD 1, PSA 12.03, QED 0.28
Compound (SMILES): NCC[S+]([O-])C(c1ccccc1)c1ccccc1
InChIKey: SHMYXVVITSBKCM-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 24600 nM (pChEMBL 4.610000133514404)
Descriptors: MW 259.37, ALogP 2.48, HBA 2, HBD 1, PSA 49.08, QED 0.84
Compound (SMILES): CCCNC(=O)CSC(c1ccc(Br)cc1)c1ccc(Br)cc1
InChIKey: RLOKHFJDXSAUHJ-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 10600 nM (pChEMBL 4.96999979019165)
Descriptors: MW 457.23, ALogP 5.56, HBA 2, HBD 1, PSA 29.1, QED 0.59
Compound (SMILES): O=C(CSC(c1ccccc1)c1ccccc1)NCC1CC1
InChIKey: OWMIZUYHYVMPAZ-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Norepinephrine Transporter Binding Assay. Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000×g for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.). Each compound was tested with concentrations ranging from 0.01 nM to 100 mM for competition against binding of [3H]Nisoxetine, in at least three independent experiments, each performed in triplicate. Data were analyzed by using GraphPad Prism software (San Diego, Calif.) [11; Zou et. al. J. Med. Chem. 2006, 49, 6391-6399]. The results of the in vitro assays, grouped by functionality into the amides and amines are presented in Tables 1 and 2, respectively. All compounds were tested as racemic mixtures.
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 311.45, ALogP 4.04, HBA 2, HBD 1, PSA 29.1, QED 0.84
Compound (SMILES): O=C(CSC(c1ccc(F)cc1)c1ccc(F)cc1)NCC1CC1
InChIKey: HXAYHHZCOCOHSM-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN35,428 from Sprague-Dawley rat brain DAT after 120 mins by liquid scintillation counting analysis
Measurement: Ki = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 347.43, ALogP 4.31, HBA 2, HBD 1, PSA 29.1, QED 0.81
Compound (SMILES): O=C(CSC(c1ccc(Br)cc1)c1ccc(Br)cc1)NCC1CC1
InChIKey: LAPOCEPBSTYUAE-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN35,428 from Sprague-Dawley rat brain DAT after 120 mins by liquid scintillation counting analysis
Measurement: Ki = 975 nM (pChEMBL 6.010000228881836)
Descriptors: MW 469.24, ALogP 5.56, HBA 2, HBD 1, PSA 29.1, QED 0.58
Compound (SMILES): CCCCNC(=O)CSC(c1ccccc1)c1ccccc1
InChIKey: GXTBGRNCCGYWLS-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 313.47, ALogP 4.43, HBA 2, HBD 1, PSA 29.1, QED 0.73
Compound (SMILES): CCCCNC(=O)CSC(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: QVIGDMVJIKWUSA-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]WIN35,428 from Sprague-Dawley rat brain DAT after 120 mins by liquid scintillation counting analysis
Measurement: Ki = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 349.45, ALogP 4.7, HBA 2, HBD 1, PSA 29.1, QED 0.7
Compound (SMILES): CCCCNC(=O)CSC(c1ccc(Br)cc1)c1ccc(Br)cc1
InChIKey: PZLJZRXGHIMLHP-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 471.26, ALogP 5.95, HBA 2, HBD 1, PSA 29.1, QED 0.48
Compound (SMILES): O=C(CSC(c1ccc(F)cc1)c1ccc(F)cc1)NCCCc1ccccc1
InChIKey: YPEAZIZEEHIOJQ-UHFFFAOYSA-N
Target: Transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63380
Assay: Norepinephrine Transporter Binding Assay: Brains from male Sprague-Dawley rats weighing 200-225 g (Taconic Labs, Germantown, N.Y.) were removed, frontal cortex dissected and rapidly frozen. Membranes were prepared by homogenizing tissues in 20 volumes (w/v) of 50 mM Tris containing 120 mM NaCl and 5 mM KCl, (pH 7.4 at 25° C.), using a Brinkman Polytron and centrifuged at 50,000xg for 10 min at 4° C. The resulting pellet was resuspended in buffer, recentrifuged and resuspended in buffer to a concentration of 80 mg/mL. Ligand binding experiments were conducted in assay tubes containing 0.5 mL buffer for 60 min at 0-4° C. Each tube contained 0.5 nM [3H]Nisoxetine (PerkinElmer Life Sciences, Boston, Mass.) and 8 mg frontal cortex tissue (original wet weight). Nonspecific binding was determined using 1 mM desipramine. Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.05% polyethylenimine, using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, Md.). The filters were washed twice with 3 mL cold buffer and transferred to scintillation vials. Beckman Ready Value (3.0 mL) was added and the vials were counted using a Beckman 6000 liquid scintillation counter (Beckman Coulter Instruments, Fullerton, Calif.).
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 411.52, ALogP 5.54, HBA 2, HBD 1, PSA 29.1, QED 0.47