DEXOXADROL

ID: ALA1165411

Max Phase: Unknown

Molecular Formula: C20H23NO2

Molecular Weight: 309.41

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (2): Dexoxadrol | Dioxadrol
Synonyms from Alternative Forms(2):

    Canonical SMILES:  c1ccc(C2(c3ccccc3)OC[C@H]([C@@H]3CCCCN3)O2)cc1

    Standard InChI:  InChI=1S/C20H23NO2/c1-3-9-16(10-4-1)20(17-11-5-2-6-12-17)22-15-19(23-20)18-13-7-8-14-21-18/h1-6,9-12,18-19,21H,7-8,13-15H2/t18-,19+/m0/s1

    Standard InChI Key:  HGKAMARNFGKMLC-RBUKOAKNSA-N

    Associated Targets(Human)

    Glutamate NMDA receptor; GRIN1/GRIN2A 719 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Glutamate NMDA receptor; GRIN1/GRIN2B 726 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Glutamate [NMDA] receptor subunit epsilon 2 467 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    Glutamate NMDA receptor 6467 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Rattus norvegicus 775804 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Sigma-1 receptor 3326 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Sigma intracellular receptor 2 922 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: 309.41Molecular Weight (Monoisotopic): 309.1729AlogP: 3.45#Rotatable Bonds: 3
    Polar Surface Area: 30.49Molecular Species: BASEHBA: 3HBD: 1
    #RO5 Violations: 0HBA (Lipinski): 3HBD (Lipinski): 1#RO5 Violations (Lipinski): 0
    CX Acidic pKa: CX Basic pKa: 9.68CX LogP: 4.52CX LogD: 2.28
    Aromatic Rings: 2Heavy Atoms: 23QED Weighted: 0.94Np Likeness Score: 0.69

    References

    1. Thurkauf A, Mattson MV, Richardson S, Mirsadeghi S, Ornstein PL, Harrison EA, Rice KC, Jacobson AE, Monn JA..  (1992)  Analogues of the dioxolanes dexoxadrol and etoxadrol as potential phencyclidine-like agents. Synthesis and structure-activity relationships.,  35  (8): [PMID:1349351] [10.1021/jm00086a001]
    2. Thurkauf A, Zenk PC, Balster RL, May EL, George C, Carroll FI, Mascarella SW, Rice KC, Jacobson AE, Mattson MV..  (1988)  Synthesis, absolute configuration, and molecular modeling study of etoxadrol, a potent phencyclidine-like agonist.,  31  (12): [PMID:2903930] [10.1021/jm00120a004]
    3. Banerjee A, Schepmann D, Wünsch B..  (2010)  Synthesis and NMDA receptor affinity of fluorinated dioxadrol analogues.,  18  (11): [PMID:20451396] [10.1016/j.bmc.2010.04.002]
    4. Banerjee A, Schepmann D, Köhler J, Würthwein EU, Wünsch B..  (2010)  Synthesis and SAR studies of chiral non-racemic dexoxadrol analogues as uncompetitive NMDA receptor antagonists.,  18  (22): [PMID:20965735] [10.1016/j.bmc.2010.09.047]
    5. Banerjee A, Schepmann D, Köhler J, Würthwein EU, Wünsch B..  (2010)  Synthesis and SAR studies of chiral non-racemic dexoxadrol analogues as uncompetitive NMDA receptor antagonists.,  18  (22): [PMID:20965735] [10.1016/j.bmc.2010.09.047]
    6. Tewes B, Frehland B, Schepmann D, Schmidtke KU, Winckler T, Wünsch B..  (2010)  Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols.,  18  (22): [PMID:20965739] [10.1016/j.bmc.2010.09.026]
    7. Utech T, Köhler J, Wünsch B..  (2011)  Synthesis of 4-(aminoalkyl) substituted 1,3-dioxanes as potent NMDA and σ receptor antagonists.,  46  (6): [PMID:21444132] [10.1016/j.ejmech.2011.02.070]
    8. Köhler J, Bergander K, Fabian J, Schepmann D, Wünsch B..  (2012)  Enantiomerically pure 1,3-dioxanes as highly selective NMDA and σ₁ receptor ligands.,  55  (20): [PMID:23013229] [10.1021/jm301166m]
    9. Banerjee A, Frohlich R, Schepmann D, Wunsch B.  (2010)  Synthesis and NMDA receptor affinity of dexoxadrol analogues with modifications in position 4 of the piperidine ring,  (1): [10.1039/C0MD00017E]
    10. Gawaskar S, Schepmann D, Bonifazi A, Wünsch B..  (2014)  Synthesis, GluN2B affinity and selectivity of benzo[7]annulen-7-amines.,  22  (23): [PMID:25458498] [10.1016/j.bmc.2014.10.004]
    11. Bourgeois C, Werfel E, Galla F, Lehmkuhl K, Torres-Gómez H, Schepmann D, Kögel B, Christoph T, Straßburger W, Englberger W, Soeberdt M, Hüwel S, Galla HJ, Wünsch B..  (2014)  Synthesis and pharmacological evaluation of 5-pyrrolidinylquinoxalines as a novel class of peripherally restricted κ-opioid receptor agonists.,  57  (15): [PMID:25062506] [10.1021/jm500940q]
    12. Bonifazi A, Del Bello F, Mammoli V, Piergentili A, Petrelli R, Cimarelli C, Pellei M, Schepmann D, Wünsch B, Barocelli E, Bertoni S, Flammini L, Amantini C, Nabissi M, Santoni G, Vistoli G, Quaglia W..  (2015)  Novel Potent N-Methyl-d-aspartate (NMDA) Receptor Antagonists or σ1 Receptor Ligands Based on Properly Substituted 1,4-Dioxane Ring.,  58  (21): [PMID:26430967] [10.1021/acs.jmedchem.5b01214]
    13. Gawaskar S, Schepmann D, Bonifazi A, Robaa D, Sippl W, Wünsch B..  (2015)  Benzo[7]annulene-based GluN2B selective NMDA receptor antagonists: Surprising effect of a nitro group in 2-position.,  25  (24): [PMID:26531150] [10.1016/j.bmcl.2015.10.076]
    14. Dey S, Schepmann D, Wünsch B..  (2016)  Role of the phenolic OH moiety of GluN2B-selective NMDA antagonists with 3-benzazepine scaffold.,  26  (3): [PMID:26750254] [10.1016/j.bmcl.2015.12.067]
    15. Galla F, Bourgeois C, Lehmkuhl K, Schepmann D, Soeberdt M, Lotts T, Abels C, Stander S, Wunsch B.  (2016)  Effects of polar receptor agonists designed for the periphery on ATP-induced Ca2+release from keratinocytes,  (2): [10.1039/C5MD00414D]
    16. Rath S, Schepmann D, Wünsch B..  (2017)  Replacement of benzylic hydroxy group by vinyl or hydroxymethyl moiety at the 3-benzazepine scaffold retaining GluN2B affinity.,  25  (20): [PMID:28797770] [10.1016/j.bmc.2017.07.059]
    17. Dey S, Schepmann D, Wünsch B..  (2018)  2-Methyltetrahydro-3-benzazepin-1-ols - The missing link in SAR of GluN2B selective NMDA receptor antagonists.,  26  (2): [PMID:29254894] [10.1016/j.bmc.2017.12.010]
    18. Dey S, Temme L, Schreiber JA, Schepmann D, Frehland B, Lehmkuhl K, Strutz-Seebohm N, Seebohm G, Wünsch B..  (2017)  Deconstruction - reconstruction approach to analyze the essential structural elements of tetrahydro-3-benzazepine-based antagonists of GluN2B subunit containing NMDA receptors.,  138  [PMID:28704758] [10.1016/j.ejmech.2017.06.068]
    19. Temme L, Frehland B, Schepmann D, Robaa D, Sippl W, Wünsch B..  (2018)  Hydroxymethyl bioisosteres of phenolic GluN2B-selective NMDA receptor antagonists: Design, synthesis and pharmacological evaluation.,  144  [PMID:29289890] [10.1016/j.ejmech.2017.12.054]
    20. Shuto Y, Thum S, Temme L, Schepmann D, Kitamura M, Wünsch B..  (2017)  Do GluN2B subunit containing NMDA receptors tolerate a fluorine atom in the phenylalkyl side chain?,  (5): [PMID:30108812] [10.1039/C6MD00621C]
    21. Temme L, Börgel F, Schepmann D, Robaa D, Sippl W, Daniliuc C, Wünsch B..  (2019)  Impact of hydroxy moieties at the benzo[7]annulene ring system of GluN2B ligands: Design, synthesis and biological evaluation.,  27  (23): [PMID:31648876] [10.1016/j.bmc.2019.115146]
    22. Wagner M, Schepmann D, Ametamey SM, Wünsch B..  (2019)  Modification of the 4-phenylbutyl side chain of potent 3-benzazepine-based GluN2B receptor antagonists.,  27  (16): [PMID:31255496] [10.1016/j.bmc.2019.06.035]
    23. Thum S, Schepmann D, Ayet E, Pujol M, Nieto FR, Ametamey SM, Wünsch B..  (2019)  Tetrahydro-3-benzazepines with fluorinated side chains as NMDA and σ1 receptor antagonists: Synthesis, receptor affinity, selectivity and antiallodynic activity.,  177  [PMID:31129453] [10.1016/j.ejmech.2019.05.034]

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