CINNAMIC ACID HYDROXAMATE

ID: ALA237370

Max Phase: Preclinical

Molecular Formula: C9H7Cl2NO2

Molecular Weight: 232.07

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (5): 2,4-Dichlorocinnamic Hydroxamate | 2,4-Dichlorocinnamic Hydroxamic Acid | 2,4-Dichlorocinnamichydroxamic Acid | 2,4-Dichlorocinnamyl Hydroxamic Acid | Cinnamic Acid Hydroxamate
Synonyms from Alternative Forms(5):

    Canonical SMILES:  O=C(/C=C/c1ccc(Cl)cc1Cl)NO

    Standard InChI:  InChI=1S/C9H7Cl2NO2/c10-7-3-1-6(8(11)5-7)2-4-9(13)12-14/h1-5,14H,(H,12,13)/b4-2+

    Standard InChI Key:  LHTLDFWBUPYUDR-DUXPYHPUSA-N

    Associated Targets(Human)

    TF Tbio Serotransferrin (88 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    PRSS1 Tclin Trypsin (2137 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    HDAC2 Tclin Histone deacetylase 2 (3971 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    CA2 Tclin Carbonic anhydrase II (17698 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    MMP12 Tchem Matrix metalloproteinase 12 (1130 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    MMP2 Tchem Matrix metalloproteinase-2 (6627 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    Plasma (7708 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    Mus musculus (284745 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    botA Botulinum neurotoxin type A (1303 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    PPO2 Tyrosinase (3884 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    Hepatitis C virus (23859 Activities)
    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
    Plasma (10718 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: 232.07Molecular Weight (Monoisotopic): 230.9854AlogP: 2.51#Rotatable Bonds: 2
    Polar Surface Area: 49.33Molecular Species: NEUTRALHBA: 2HBD: 2
    #RO5 Violations: 0HBA (Lipinski): 3HBD (Lipinski): 2#RO5 Violations (Lipinski): 0
    CX Acidic pKa: 9.55CX Basic pKa: CX LogP: 2.53CX LogD: 2.53
    Aromatic Rings: 1Heavy Atoms: 14QED Weighted: 0.47Np Likeness Score: -0.87

    References

    1. Capková K, Yoneda Y, Dickerson TJ, Janda KD..  (2007)  Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors.,  17  (23): [PMID:17951059] [10.1016/j.bmcl.2007.09.103]
    2. Eubanks LM, Hixon MS, Jin W, Hong S, Clancy CM, Tepp WH, Baldwin MR, Malizio CJ, Goodnough MC, Barbieri JT, Johnson EA, Boger DL, Dickerson TJ, Janda KD..  (2007)  An in vitro and in vivo disconnect uncovered through high-throughput identification of botulinum neurotoxin A antagonists.,  104  (8): [PMID:17293454] [10.1073/pnas.0611213104]
    3. Moe ST, Thompson AB, Smith GM, Fredenburg RA, Stein RL, Jacobson AR..  (2009)  Botulinum neurotoxin serotype A inhibitors: small-molecule mercaptoacetamide analogs.,  17  (8): [PMID:19329331] [10.1016/j.bmc.2009.03.013]
    4. Burnett JC, Wang C, Nuss JE, Nguyen TL, Hermone AR, Schmidt JJ, Gussio R, Wipf P, Bavari S..  (2009)  Pharmacophore-guided lead optimization: the rational design of a non-zinc coordinating, sub-micromolar inhibitor of the botulinum neurotoxin serotype a metalloprotease.,  19  (19): [PMID:19703771] [10.1016/j.bmcl.2009.01.111]
    5. Capková K, Hixon MS, Pellett S, Barbieri JT, Johnson EA, Janda KD..  (2010)  Benzylidene cyclopentenediones: First irreversible inhibitors against botulinum neurotoxin A's zinc endopeptidase.,  20  (1): [PMID:19914829] [10.1016/j.bmcl.2009.10.129]
    6. Li B, Pai R, Cardinale SC, Butler MM, Peet NP, Moir DT, Bavari S, Bowlin TL..  (2010)  Synthesis and biological evaluation of botulinum neurotoxin a protease inhibitors.,  53  (5): [PMID:20155918] [10.1021/jm901852f]
    7. Smith GR, Caglič D, Capek P, Zhang Y, Godbole S, Reitz AB, Dickerson TJ..  (2012)  Reexamining hydroxamate inhibitors of botulinum neurotoxin serotype A: extending towards the β-exosite.,  22  (11): [PMID:22542019] [10.1016/j.bmcl.2012.04.019]
    8. Silhár P, Lardy MA, Hixon MS, Shoemaker CB, Barbieri JT, Struss AK, Lively JM, Javor S, Janda KD..  (2013)  The C-terminus of Botulinum A Protease Has Profound and Unanticipated Kinetic Consequences Upon the Catalytic Cleft.,  (2): [PMID:23565325] [10.1021/ml300428s]
    9. Šilhár P, Silvaggi NR, Pellett S, Čapková K, Johnson EA, Allen KN, Janda KD..  (2013)  Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: synthesis, crystallography, modeling, kinetic and cellular based studies.,  21  (5): [PMID:23340139] [10.1016/j.bmc.2012.12.001]
    10. Day JA, Cohen SM..  (2013)  Investigating the selectivity of metalloenzyme inhibitors.,  56  (20): [PMID:24074025] [10.1021/jm401053m]
    11. Videnović M, Opsenica DM, Burnett JC, Gomba L, Nuss JE, Selaković Z, Konstantinović J, Krstić M, Segan S, Zlatović M, Sciotti RJ, Bavari S, Solaja BA..  (2014)  Second generation steroidal 4-aminoquinolines are potent, dual-target inhibitors of the botulinum neurotoxin serotype A metalloprotease and P. falciparum malaria.,  57  (10): [PMID:24742203] [10.1021/jm500033r]
    12. Ai T, Xu Y, Qiu L, Geraghty RJ, Chen L..  (2015)  Hydroxamic acids block replication of hepatitis C virus.,  58  (2): [PMID:25490700] [10.1021/jm501330g]
    13. Hermant P, Bosc D, Piveteau C, Gealageas R, Lam B, Ronco C, Roignant M, Tolojanahary H, Jean L, Renard PY, Lemdani M, Bourotte M, Herledan A, Bedart C, Biela A, Leroux F, Deprez B, Deprez-Poulain R..  (2017)  Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox.,  60  (21): [PMID:28985084] [10.1021/acs.jmedchem.7b01444]
    14. Zhou Y, McGillick BE, Teng YG, Haranahalli K, Ojima I, Swaminathan S, Rizzo RC..  (2016)  Identification of small molecule inhibitors of botulinum neurotoxin serotype E via footprint similarity.,  24  (20): [PMID:27543389] [10.1016/j.bmc.2016.07.031]
    15. Lin L,Olson ME,Sugane T,Turner LD,Tararina MA,Nielsen AL,Kurbanov EK,Pellett S,Johnson EA,Cohen SM,Allen KN,Janda KD.  (2020)  Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A.,  63  (19.0): [PMID:32886509] [10.1021/acs.jmedchem.0c01006]
    16. Turner, Lewis D., Nielsen, Alexander L., Lin, Lucy, Pellett, Sabine, Sugane, Takashi, Olson, Margaret E., Johnson, Eric A., Janda, Kim D..  (2021)  Irreversible inhibition of BoNT/A protease: proximity-driven reactivity contingent upon a bifunctional approach,  12  (6.0): [PMID:34223161] [10.1039/d1md00089f]
    17. Turner LD, Nielsen AL, Lin L, Campedelli AJ, Silvaggi NR, Chen JS, Wakefield AE, Allen KN, Janda KD..  (2021)  Use of Crystallography and Molecular Modeling for the Inhibition of the Botulinum Neurotoxin A Protease.,  12  (8.0): [PMID:34413962] [10.1021/acsmedchemlett.1c00325]
    18. Patel EN, Turner LD, Hixon MS, Janda KD..  (2022)  Identification of Slow-Binding Inhibitors of the BoNT/A Protease.,  13  (4.0): [PMID:35450355] [10.1021/acsmedchemlett.2c00028]
    19. Hou R, He Y, Yan G, Hou S, Xie Z, Liao C..  (2021)  Zinc enzymes in medicinal chemistry.,  226  [PMID:34624823] [10.1016/j.ejmech.2021.113877]

    Source