RO-54864

ID: ALA286346

Max Phase: Preclinical

Molecular Formula: C16H12Cl2N2O

Molecular Weight: 319.19

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (1): Ro-5-4864
Synonyms from Alternative Forms(1):

    Canonical SMILES:  CN1C(=O)CN=C(c2ccc(Cl)cc2)c2cc(Cl)ccc21

    Standard InChI:  InChI=1S/C16H12Cl2N2O/c1-20-14-7-6-12(18)8-13(14)16(19-9-15(20)21)10-2-4-11(17)5-3-10/h2-8H,9H2,1H3

    Standard InChI Key:  PUMYFTJOWAJIKF-UHFFFAOYSA-N

    Associated Targets(Human)

    SF-126 160 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SF-188 17 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Ramos 1218 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    A2058 690 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HeLa 62764 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Jurkat 10389 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Translocator protein 484 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    U-937 7138 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Prelamin-A/C 36751 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Lysosomal alpha-glucosidase 35701 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 93046 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    ATPase family AAA domain-containing protein 5 122566 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Importin subunit beta-1/Snurportin-1 25097 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Geminin 128009 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Tyrosyl-DNA phosphodiesterase 1 345557 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Alpha-synuclein 10960 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Isocitrate dehydrogenase [NADP] cytoplasmic 40980 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    C6 2371 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    RG2 196 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Peripheral-type benzodiazepine receptor 1942 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Y-1 9 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    GABA-A receptor; anion channel 5731 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Peripheral-type benzodiazepine receptor 243 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Nonstructural protein 1 33327 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Plasmodium falciparum 966862 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Mus musculus 284745 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HT-22 3261 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Molecule Features

    Natural Product: YesOral: NoChemical Probe: NoParenteral: No
    Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
    Chirality: NoAvailability: NoProdrug: No

    Drug Indications

    MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

    Mechanisms of Action

    Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

    Properties

    Molecular Weight: 319.19Molecular Weight (Monoisotopic): 318.0327AlogP: 3.81#Rotatable Bonds: 1
    Polar Surface Area: 32.67Molecular Species: NEUTRALHBA: 2HBD: 0
    #RO5 Violations: 0HBA (Lipinski): 3HBD (Lipinski): 0#RO5 Violations (Lipinski): 0
    CX Acidic pKa: CX Basic pKa: 2.45CX LogP: 3.68CX LogD: 3.68
    Aromatic Rings: 2Heavy Atoms: 21QED Weighted: 0.79Np Likeness Score: -0.52

    References

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    2. Kupczyk-Subotkowska L, Siahaan TJ, Basile AS, Friedman HS, Higgins PE, Song D, Gallo JM..  (1997)  Modulation of melphalan resistance in glioma cells with a peripheral benzodiazepine receptor ligand-melphalan conjugate.,  40  (11): [PMID:9171882] [10.1021/jm960592p]
    3. Primofiore G, Da Settimo F, Taliani S, Simorini F, Patrizi MP, Novellino E, Greco G, Abignente E, Costa B, Chelli B, Martini C..  (2004)  N,N-dialkyl-2-phenylindol-3-ylglyoxylamides. A new class of potent and selective ligands at the peripheral benzodiazepine receptor.,  47  (7): [PMID:15027878] [10.1021/jm030973k]
    4. Van Dort ME, Ciliax BJ, Gildersleeve DL, Sherman PS, Rosenspire KC, Young AB, Junck L, Wieland DM..  (1988)  Radioiodinated benzodiazepines: agents for mapping glial tumors.,  31  (11): [PMID:2846836] [10.1021/jm00119a005]
    5. TenBrink RE, Bergh CL, Duncan JN, Harris DW, Huff RM, Lahti RA, Lawson CF, Lutzke BS, Martin IJ, Rees SA, Schlachter SK, Sih JC, Smith MW..  (1996)  (S)-(-)-4-[4-[2-(isochroman-1-yl)ethyl]-piperazin-1-yl] benzenesulfonamide, a selective dopamine D4 antagonist.,  39  (13): [PMID:8691438] [10.1021/jm960084f]
    6. Boitano A, Emal CD, Leonetti F, Blatt NB, Dineen TA, Ellman JA, Roush WR, Opipari AW, Glick GD..  (2003)  Structure activity studies of a novel cytotoxic benzodiazepine.,  13  (19): [PMID:12951119] [10.1016/s0960-894x(03)00683-8]
    7. Campiani G, Nacci V, Fiorini I, De Filippis MP, Garofalo A, Ciani SM, Greco G, Novellino E, Williams DC, Zisterer DM, Woods MJ, Mihai C, Manzoni C, Mennini T..  (1996)  Synthesis, biological activity, and SARs of pyrrolobenzoxazepine derivatives, a new class of specific "peripheral-type" benzodiazepine receptor ligands.,  39  (18): [PMID:8784441] [10.1021/jm960251b]
    8. Dalpiaz A, Bertolasi V, Borea PA, Nacci V, Fiorini I, Campiani G, Mennini T, Manzoni C, Novellino E, Greco G..  (1995)  A concerted study using binding measurements, X-ray structural data, and molecular modeling on the stereochemical features responsible for the affinity of 6-arylpyrrolo[2,1-d][1,5]benzothiazepines toward mitochondrial benzodiazepine receptors.,  38  (23): [PMID:7473601] [10.1021/jm00023a013]
    9. Mohler ML, Kang GS, Hong SS, Patil R, Kirichenko OV, Li W, Rakov IM, Geisert EE, Miller DD..  (2006)  Discovery of antiglioma activity of biaryl 1,2,3,4-tetrahydroisoquinoline derivatives and conformationally flexible analogues.,  49  (19): [PMID:16970409] [10.1021/jm060020x]
    10. Taliani S, Simorini F, Sergianni V, La Motta C, Da Settimo F, Cosimelli B, Abignente E, Greco G, Novellino E, Rossi L, Gremigni V, Spinetti F, Chelli B, Martini C..  (2007)  New fluorescent 2-phenylindolglyoxylamide derivatives as probes targeting the peripheral-type benzodiazepine receptor: design, synthesis, and biological evaluation.,  50  (2): [PMID:17228885] [10.1021/jm061137o]
    11. Dourlat J, Liu WQ, Gresh N, Garbay C..  (2007)  Novel 1,4-benzodiazepine derivatives with antiproliferative properties on tumor cell lines.,  17  (9): [PMID:17317183] [10.1016/j.bmcl.2007.02.016]
    12. Cleary J, Johnson KM, Opipari AW, Glick GD..  (2007)  Inhibition of the mitochondrial F1F0-ATPase by ligands of the peripheral benzodiazepine receptor.,  17  (6): [PMID:17251020] [10.1016/j.bmcl.2006.12.102]
    13. Da Settimo F, Simorini F, Taliani S, La Motta C, Marini AM, Salerno S, Bellandi M, Novellino E, Greco G, Cosimelli B, Da Pozzo E, Costa B, Simola N, Morelli M, Martini C..  (2008)  Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis.,  51  (18): [PMID:18729350] [10.1021/jm8003224]
    14. Scarf AM, Ittner LM, Kassiou M..  (2009)  The translocator protein (18 kDa): central nervous system disease and drug design.,  52  (3): [PMID:19133775] [10.1021/jm8011678]
    15. Yu W, Wang E, Voll RJ, Miller AH, Goodman MM..  (2008)  Synthesis, fluorine-18 radiolabeling, and in vitro characterization of 1-iodophenyl-N-methyl-N-fluoroalkyl-3-isoquinoline carboxamide derivatives as potential PET radioligands for imaging peripheral benzodiazepine receptor.,  16  (11): [PMID:18472268] [10.1016/j.bmc.2008.04.046]
    16. Taliani S, Da Pozzo E, Bellandi M, Bendinelli S, Pugliesi I, Simorini F, La Motta C, Salerno S, Marini AM, Da Settimo F, Cosimelli B, Greco G, Novellino E, Martini C..  (2010)  Novel irreversible fluorescent probes targeting the 18 kDa translocator protein: synthesis and biological characterization.,  53  (10): [PMID:20438080] [10.1021/jm100100q]
    17. PubChem BioAssay data set, 
    18. Pike VW, Taliani S, Lohith TG, Owen DR, Pugliesi I, Da Pozzo E, Hong J, Zoghbi SS, Gunn RN, Parker CA, Rabiner EA, Fujita M, Innis RB, Martini C, Da Settimo F..  (2011)  Evaluation of novel N1-methyl-2-phenylindol-3-ylglyoxylamides as a new chemotype of 18 kDa translocator protein-selective ligand suitable for the development of positron emission tomography radioligands.,  54  (1): [PMID:21133364] [10.1021/jm101230g]
    19. Cosimelli B, Simorini F, Taliani S, La Motta C, Da Settimo F, Severi E, Greco G, Novellino E, Costa B, Da Pozzo E, Bendinelli S, Martini C..  (2011)  Tertiary amides with a five-membered heteroaromatic ring as new probes for the translocator protein.,  46  (9): [PMID:21824692] [10.1016/j.ejmech.2011.07.025]
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    21. Castellano S, Taliani S, Milite C, Pugliesi I, Da Pozzo E, Rizzetto E, Bendinelli S, Costa B, Cosconati S, Greco G, Novellino E, Sbardella G, Stefancich G, Martini C, Da Settimo F..  (2012)  Synthesis and biological evaluation of 4-phenylquinazoline-2-carboxamides designed as a novel class of potent ligands of the translocator protein.,  55  (9): [PMID:22489952] [10.1021/jm201703k]
    22. Fukaya T, Kodo T, Ishiyama T, Kakuyama H, Nishikawa H, Baba S, Masumoto S..  (2012)  Design, synthesis and structure-activity relationships of novel benzoxazolone derivatives as 18 kDa translocator protein (TSPO) ligands.,  20  (18): [PMID:22884355] [10.1016/j.bmc.2012.07.023]
    23. Castellano S, Taliani S, Viviano M, Milite C, Da Pozzo E, Costa B, Barresi E, Bruno A, Cosconati S, Marinelli L, Greco G, Novellino E, Sbardella G, Da Settimo F, Martini C..  (2014)  Structure-activity relationship refinement and further assessment of 4-phenylquinazoline-2-carboxamide translocator protein ligands as antiproliferative agents in human glioblastoma tumors.,  57  (6): [PMID:24580635] [10.1021/jm401721h]
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    25. Barresi E, Bruno A, Taliani S, Cosconati S, Da Pozzo E, Salerno S, Simorini F, Daniele S, Giacomelli C, Marini AM, La Motta C, Marinelli L, Cosimelli B, Novellino E, Greco G, Da Settimo F, Martini C..  (2015)  Deepening the Topology of the Translocator Protein Binding Site by Novel N,N-Dialkyl-2-arylindol-3-ylglyoxylamides.,  58  (15): [PMID:26177193] [10.1021/acs.jmedchem.5b00689]
    26. Kim T, Son WS, Morshed MN, Londhe AM, Jung SY, Park JH, Park WK, Lim SM, Park KD, Cho SJ, Jeong KS, Lee J, Pae AN..  (2017)  Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function against Aβ-induced neurotoxicity.,  141  [PMID:29031071] [10.1016/j.ejmech.2017.09.033]
    27. Robello M, Barresi E, Baglini E, Salerno S, Taliani S, Settimo FD..  (2021)  The Alpha Keto Amide Moiety as a Privileged Motif in Medicinal Chemistry: Current Insights and Emerging Opportunities.,  64  (7.0): [PMID:33764065] [10.1021/acs.jmedchem.0c01808]
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