OBIDOXIME CHLORIDE

ID: ALA291233

Max Phase: Phase

Molecular Formula: C14H16Cl2N4O3

Molecular Weight: 288.31

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (2): Obidoxime chloride | NSC-757237
Synonyms from Alternative Forms(2):

    Canonical SMILES:  O/N=C/c1cc[n+](COC[n+]2ccc(/C=N/O)cc2)cc1.[Cl-].[Cl-]

    Standard InChI:  InChI=1S/C14H14N4O3.2ClH/c19-15-9-13-1-5-17(6-2-13)11-21-12-18-7-3-14(4-8-18)10-16-20;;/h1-10H,11-12H2;2*1H

    Standard InChI Key:  ZIFJVJZWVSPZLE-UHFFFAOYSA-N

    Associated Targets(Human)

    Acetylcholinesterase 18204 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Homo sapiens 32628 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cholinesterases; ACHE & BCHE 1222 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Butyrylcholinesterase 7174 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    Acetylcholinesterase 12221 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Acetylcholinesterase 1035 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Anguilliformes 23 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Acetylcholinesterase 2577 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Rattus norvegicus 775804 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Acetylcholinesterase 8 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Mus musculus 284745 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cavia porcellus 23802 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Oryctolagus cuniculus 11301 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SARS-CoV-2 38078 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Replicase polyprotein 1ab 11336 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: YesAvailability: 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: 288.31Molecular Weight (Monoisotopic): 288.1211AlogP: 0.51#Rotatable Bonds: 6
    Polar Surface Area: 82.17Molecular Species: NEUTRALHBA: 5HBD: 2
    #RO5 Violations: 0HBA (Lipinski): 7HBD (Lipinski): 2#RO5 Violations (Lipinski): 0
    CX Acidic pKa: 7.51CX Basic pKa: 1.05CX LogP: -6.93CX LogD: -7.19
    Aromatic Rings: 2Heavy Atoms: 21QED Weighted: 0.35Np Likeness Score: -0.11

    References

    1. Bedford CD, Harris RN, Howd RA, Miller A, Nolen HW, Kenley RA..  (1984)  Structure-activity relationships for reactivators of organophosphorus-inhibited acetylcholinesterase: quaternary salts of 2-[(hydroxyimino)methyl]imidazole.,  27  (11): [PMID:6492073] [10.1021/jm00377a010]
    2. Bedford CD, Miura M, Bottaro JC, Howd RA, Nolen HW..  (1986)  Nonquaternary cholinesterase reactivators. 4. Dialkylaminoalkyl thioesters of alpha-keto thiohydroximic acids as reactivators of ethyl methylphosphonyl- and 1,2,2-trimethylpropyl methylphosphonyl-acetylcholinesterase in vitro.,  29  (9): [PMID:3746817] [10.1021/jm00159a021]
    3. Kuca K, Bielavský J, Cabal J, Kassa J..  (2003)  Synthesis of a new reactivator of tabun-inhibited acetylcholinesterase.,  13  (20): [PMID:14505667] [10.1016/s0960-894x(03)00751-0]
    4. Bedford CD, Harris RN, Howd RA, Goff DA, Koolpe GA, Petesch M, Miller A, Nolen HW, Musallam HA, Pick RO..  (1989)  Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 2. Preparation and in vitro and in vivo evaluation of 1-(alkoxymethyl)-2-[(hydroxyimino)methyl]-3-methylimida zolium halides for reactivation of organophosphorus-inhibited acetylcholinesterases.,  32  (2): [PMID:2913310] [10.1021/jm00122a034]
    5. Musilek K, Kuca K, Jun D, Dohnal V, Dolezal M, Dolezal M..  (2006)  Synthesis of the novel series of bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase.,  16  (3): [PMID:16288867] [10.1016/j.bmcl.2005.10.059]
    6. Musilek K, Holas O, Kuca K, Jun D, Dohnal V, Dolezal M, Dolezal M..  (2006)  Synthesis of asymmetrical bispyridinium compounds bearing cyano-moiety and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase.,  16  (21): [PMID:16934462] [10.1016/j.bmcl.2006.08.011]
    7. Musilek K, Holas O, Jun D, Dohnal V, Gunn-Moore F, Opletalova V, Dolezal M, Dolezal M, Kuca K..  (2007)  Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker: preparation and reactivation of tabun- and paraoxon-inhibited acetylcholinesterase.,  15  (21): [PMID:17764957] [10.1016/j.bmc.2007.08.002]
    8. Musilek K, Jun D, Cabal J, Kassa J, Gunn-Moore F, Kuca K..  (2007)  Design of a potent reactivator of tabun-inhibited acetylcholinesterase--synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203).,  50  (22): [PMID:17924614] [10.1021/jm070653r]
    9. Musilek K, Holas O, Kuca K, Jun D, Dohnal V, Opletalova V, Dolezal M, Dolezal M..  (2007)  Novel series of bispyridinium compounds bearing a (Z)-but-2-ene linker--synthesis and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase.,  17  (11): [PMID:17383875] [10.1016/j.bmcl.2007.03.025]
    10. Musilek K, Kucera J, Jun D, Dohnal V, Opletalova V, Kuca K..  (2008)  Monoquaternary pyridinium salts with modified side chain-synthesis and evaluation on model of tabun- and paraoxon-inhibited acetylcholinesterase.,  16  (17): [PMID:18676153] [10.1016/j.bmc.2008.07.036]
    11. Acharya J, Gupta AK, Mazumder A, Dubey DK..  (2009)  In-vitro regeneration of sarin inhibited electric eel acetylcholinesterase by bis-pyridinium oximes bearing xylene linker.,  44  (3): [PMID:18396355] [10.1016/j.ejmech.2008.02.020]
    12. Acharya J, Gupta AK, Dubey DK, Raza SK..  (2009)  Synthesis and evaluation of novel bis-pyridinium oximes as reactivators of DFP-inhibited acetylcholinesterase.,  44  (3): [PMID:18396353] [10.1016/j.ejmech.2008.02.029]
    13. Butini S, Campiani G, Borriello M, Gemma S, Panico A, Persico M, Catalanotti B, Ros S, Brindisi M, Agnusdei M, Fiorini I, Nacci V, Novellino E, Belinskaya T, Saxena A, Fattorusso C..  (2008)  Exploiting protein fluctuations at the active-site gorge of human cholinesterases: further optimization of the design strategy to develop extremely potent inhibitors.,  51  (11): [PMID:18479118] [10.1021/jm701253t]
    14. Jeong HC, Kang NS, Park NJ, Yum EK, Jung YS..  (2009)  Reactivation potency of fluorinated pyridinium oximes for acetylcholinesterases inhibited by paraoxon organophosphorus agent.,  19  (4): [PMID:19124241] [10.1016/j.bmcl.2008.12.070]
    15. Musilek K, Roder J, Komloova M, Holas O, Hrabinova M, Pohanka M, Dohnal V, Opletalova V, Kuca K, Jung YS..  (2011)  Preparation, in vitro screening and molecular modelling of symmetrical 4-tert-butylpyridinium cholinesterase inhibitors--analogues of SAD-128.,  21  (1): [PMID:21144749] [10.1016/j.bmcl.2010.11.051]
    16. Musilek K, Komloova M, Holas O, Horova A, Pohanka M, Gunn-Moore F, Dohnal V, Dolezal M, Dolezal M, Kuca K..  (2011)  Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage-Preparation, in vitro screening and molecular docking.,  19  (2): [PMID:21215642] [10.1016/j.bmc.2010.12.021]
    17. Acharya J, Rana H, Kaushik MP..  (2011)  Synthesis and in vitro evaluation of xylene linked carbamoyl bis-pyridinium monooximes as reactivators of organophosphorus (OP) inhibited electric eel acetylcholinesterase (AChE).,  46  (9): [PMID:21703732] [10.1016/j.ejmech.2011.05.064]
    18. Kalisiak J, Ralph EC, Zhang J, Cashman JR..  (2011)  Amidine-oximes: reactivators for organophosphate exposure.,  54  (9): [PMID:21438612] [10.1021/jm200054r]
    19. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 
    20. Mercey G, Renou J, Verdelet T, Kliachyna M, Baati R, Gillon E, Arboléas M, Loiodice M, Nachon F, Jean L, Renard PY..  (2012)  Phenyltetrahydroisoquinoline-pyridinaldoxime conjugates as efficient uncharged reactivators for the dephosphylation of inhibited human acetylcholinesterase.,  55  (23): [PMID:23148598] [10.1021/jm3015519]
    21. Sit RK, Fokin VV, Amitai G, Sharpless KB, Taylor P, Radić Z..  (2014)  Imidazole aldoximes effective in assisting butyrylcholinesterase catalysis of organophosphate detoxification.,  57  (4): [PMID:24571195] [10.1021/jm401650z]
    22. Benschop HP, Van den Berg GR, Van Hooidonk C, De Jong LP, Kientz CE, Berends F, Kepner LA, Meeter E, Visser RP..  (1979)  Antidotes or organophosphate poisoning. 2. Thiadiazole-5-carboxaldoximes.,  22  (11): [PMID:533877] [10.1021/jm00197a006]
    23. Karade HN, Valiveti AK, Acharya J, Kaushik MP..  (2014)  Synthesis and in vitro evaluation of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide derivatives as reactivators against sarin and VX inhibited human acetylcholinesterase (hAChE).,  22  (9): [PMID:24721830] [10.1016/j.bmc.2014.03.023]
    24. Wei Z, Liu YQ, Zhou XB, Luo Y, Huang CQ, Wang YA, Zheng ZB, Li S..  (2014)  New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase.,  24  (24): [PMID:25453812] [10.1016/j.bmcl.2014.10.055]
    25. Karade HN, Raviraju G, Acharya BN, Valiveti AK, Bhalerao U, Acharya J..  (2016)  Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE).,  24  (18): [PMID:27450532] [10.1016/j.bmc.2016.07.005]
    26. de Koning MC, Joosen MJA, Worek F, Nachon F, van Grol M, Klaassen SD, Alkema DPW, Wille T, de Bruijn HM..  (2017)  Application of the Ugi Multicomponent Reaction in the Synthesis of Reactivators of Nerve Agent Inhibited Acetylcholinesterase.,  60  (22): [PMID:29091431] [10.1021/acs.jmedchem.7b01083]
    27. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]
    28. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]
    29. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]
    30. Da Silva O, Probst N, Landry C, Hanak AS, Warnault P, Coisne C, Calas AG, Gosselet F, Courageux C, Gastellier AJ, Trancart M, Baati R, Dehouck MP, Jean L, Nachon F, Renard PY, Dias J..  (2022)  A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning.,  65  (6.0): [PMID:35255209] [10.1021/acs.jmedchem.1c01748]
    31. Unpublished dataset, 
    32. Zorbaz T, Malinak D, Hofmanova T, Maraković N, Žunec S, Hrvat NM, Andrys R, Psotka M, Zandona A, Svobodova J, Prchal L, Fingler S, Katalinić M, Kovarik Z, Musilek K..  (2022)  Halogen substituents enhance oxime nucleophilicity for reactivation of cholinesterases inhibited by nerve agents.,  238  [PMID:35526478] [10.1016/j.ejmech.2022.114377]