ID: ALA463590

Max Phase: Preclinical

Molecular Formula: C23H24ClNO4

Molecular Weight: 413.90

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (1): L-742001
Synonyms from Alternative Forms(1):

    Canonical SMILES:  O=C(O)/C(O)=C/C(=O)C1(Cc2ccc(Cl)cc2)CCN(Cc2ccccc2)CC1

    Standard InChI:  InChI=1S/C23H24ClNO4/c24-19-8-6-17(7-9-19)15-23(21(27)14-20(26)22(28)29)10-12-25(13-11-23)16-18-4-2-1-3-5-18/h1-9,14,26H,10-13,15-16H2,(H,28,29)/b20-14-

    Standard InChI Key:  DGJZJCIAWLMRBY-ZHZULCJRSA-N

    Associated Targets(Human)

    HEK-293T 167025 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    unidentified influenza virus 265 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Polymerase acidic protein 806 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Influenza A virus 11224 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Polymerase acidic protein 35 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MDCK 10148 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    NIH3T3 5395 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Molecule Features

    Natural Product: NoOral: 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: 413.90Molecular Weight (Monoisotopic): 413.1394AlogP: 4.26#Rotatable Bonds: 7
    Polar Surface Area: 77.84Molecular Species: ACIDHBA: 4HBD: 2
    #RO5 Violations: 0HBA (Lipinski): 5HBD (Lipinski): 2#RO5 Violations (Lipinski): 0
    CX Acidic pKa: 2.53CX Basic pKa: 8.43CX LogP: 1.99CX LogD: 1.96
    Aromatic Rings: 2Heavy Atoms: 29QED Weighted: 0.52Np Likeness Score: -0.23

    References

    1. Prado-Prado FJ, Martinez de la Vega O, Uriarte E, Ubeira FM, Chou KC, González-Díaz H..  (2009)  Unified QSAR approach to antimicrobials. 4. Multi-target QSAR modeling and comparative multi-distance study of the giant components of antiviral drug-drug complex networks.,  17  (2): [PMID:19112024] [10.1016/j.bmc.2008.11.075]
    2. Baughman BM, Jake Slavish P, DuBois RM, Boyd VA, White SW, Webb TR..  (2012)  Identification of influenza endonuclease inhibitors using a novel fluorescence polarization assay.,  (3): [PMID:22211528] [10.1021/cb200439z]
    3. Hastings JC, Selnick H, Wolanski B, Tomassini JE..  (1996)  Anti-influenza virus activities of 4-substituted 2,4-dioxobutanoic acid inhibitors.,  40  (5): [PMID:8723491] [10.1128/aac.40.5.1304]
    4. Das K..  (2012)  Antivirals targeting influenza A virus.,  55  (14): [PMID:22612288] [10.1021/jm300455c]
    5. Yan Z, Zhang L, Fu H, Wang Z, Lin J..  (2014)  Design of the influenza virus inhibitors targeting the PA endonuclease using 3D-QSAR modeling, side-chain hopping, and docking.,  24  (2): [PMID:24365156] [10.1016/j.bmcl.2013.12.026]
    6. Fudo S, Yamamoto N, Nukaga M, Odagiri T, Tashiro M, Neya S, Hoshino T..  (2015)  Structural and computational study on inhibitory compounds for endonuclease activity of influenza virus polymerase.,  23  (17): [PMID:26252962] [10.1016/j.bmc.2015.07.046]
    7. Pala N, Stevaert A, Dallocchio R, Dessì A, Rogolino D, Carcelli M, Sanna V, Sechi M, Naesens L..  (2015)  Virtual Screening and Biological Validation of Novel Influenza Virus PA Endonuclease Inhibitors.,  (8): [PMID:26288686] [10.1021/acsmedchemlett.5b00109]
    8. Miyagawa M, Akiyama T, Mikamiyama-Iwata M, Hattori K, Kurihara N, Taoda Y, Takahashi-Kageyama C, Kurose N, Mikamiyama H, Suzuki N, Takaya K, Tomita K, Matsuo K, Morimoto K, Yoshida R, Shishido T, Yoshinaga T, Sato A, Kawai M..  (2016)  Discovery of novel 5-hydroxy-4-pyridone-3-carboxy acids as potent inhibitors of influenza Cap-dependent endonuclease.,  26  (19): [PMID:27568084] [10.1016/j.bmcl.2016.08.038]
    9. Ju H, Zhang J, Huang B, Kang D, Huang B, Liu X, Zhan P..  (2017)  Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives.,  60  (9): [PMID:28118010] [10.1021/acs.jmedchem.6b01227]
    10. Credille CV, Dick BL, Morrison CN, Stokes RW, Adamek RN, Wu NC, Wilson IA, Cohen SM..  (2018)  Structure-Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease.,  61  (22): [PMID:30351002] [10.1021/acs.jmedchem.8b01363]
    11. Ferro S, Gitto R, Buemi MR, Karamanou S, Stevaert A, Naesens L, De Luca L..  (2018)  Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening.,  26  (15): [PMID:30082105] [10.1016/j.bmc.2018.07.046]
    12. Miyagawa M, Akiyama T, Taoda Y, Takaya K, Takahashi-Kageyama C, Tomita K, Yasuo K, Hattori K, Shano S, Yoshida R, Shishido T, Yoshinaga T, Sato A, Kawai M..  (2019)  Synthesis and SAR Study of Carbamoyl Pyridone Bicycle Derivatives as Potent Inhibitors of Influenza Cap-dependent Endonuclease.,  62  (17): [PMID:31386363] [10.1021/acs.jmedchem.9b00861]
    13. Credille CV, Morrison CN, Stokes RW, Dick BL, Feng Y, Sun J, Chen Y, Cohen SM..  (2019)  SAR Exploration of Tight-Binding Inhibitors of Influenza Virus PA Endonuclease.,  62  (21): [PMID:31536340] [10.1021/acs.jmedchem.9b00747]
    14. Credille CV, Chen Y, Cohen SM..  (2016)  Fragment-Based Identification of Influenza Endonuclease Inhibitors.,  59  (13): [PMID:27291165] [10.1021/acs.jmedchem.6b00628]
    15. Zima V,Radilová K,Kožíšek M,Albiñana CB,Karlukova E,Brynda J,Fanfrlík J,Flieger M,Hodek J,Weber J,Majer P,Konvalinka J,Machara A.  (2020)  Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors.,  208  [PMID:32883638] [10.1016/j.ejmech.2020.112754]

    Source