ID: ALA1518572

Max Phase: Preclinical

Molecular Formula: C23H22N2O4

Molecular Weight: 390.44

Molecule Type: Small molecule

Representations

Synonyms (1): ZK-93423
Synonyms from Alternative Forms(1):

Canonical SMILES:  CCOC(=O)c1ncc2[nH]c3ccc(OCc4ccccc4)cc3c2c1COC

Standard InChI:  InChI=1S/C23H22N2O4/c1-3-28-23(26)22-18(14-27-2)21-17-11-16(29-13-15-7-5-4-6-8-15)9-10-19(17)25-20(21)12-24-22/h4-12,25H,3,13-14H2,1-2H3

Standard InChI Key:  ALBKMJDFBZVHAK-UHFFFAOYSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 390.44

Molecular Weight (Monoisotopic): 390.1580

AlogP: 4.62

#Rotatable Bonds: 7

Polar Surface Area: 73.44

Molecular Species: NEUTRAL

HBA: 5

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 11.72

CX Basic pKa: 2.09

CX LogP: 3.86

CX LogD: 3.86

Aromatic Rings: 4

Heavy Atoms: 29

QED Weighted: 0.47

Np Likeness Score: -0.31

References

1. Hollinshead SP, Trudell ML, Skolnick P, Cook JM..  (1990)  Structural requirements for agonist actions at the benzodiazepine receptor: studies with analogues of 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester.,  33  (3): [PMID:1968513] [10.1021/jm00165a028]

2. Diaz-Arauzo H, Evoniuk GE, Skolnick P, Cook JM..  (1991)  The agonist pharmacophore of the benzodiazepine receptor. Synthesis of a selective anticonvulsant/anxiolytic.,  34  (5): [PMID:1674542] [10.1021/jm00109a035]

3. Cox ED, Diaz-Arauzo H, Huang Q, Reddy MS, Ma C, Harris B, McKernan R, Skolnick P, Cook JM..  (1998)  Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors.,  41  (14): [PMID:9651158] [10.1021/jm970460b]

4. Zhang W, Koehler KF, Harris B, Skolnick P, Cook JM..  (1994)  Synthesis of benzo-fused benzodiazepines employed as probes of the agonist pharmacophore of benzodiazepine receptors.,  37  (6): [PMID:8145224] [10.1021/jm00032a007]

5. Huang Q, He X, Ma C, Liu R, Yu S, Dayer CA, Wenger GR, McKernan R, Cook JM..  (2000)  Pharmacophore/receptor models for GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) via a comprehensive ligand-mapping approach.,  43  (1): [PMID:10633039] [10.1021/jm990341r]

6. Wang CG, Langer T, Kamath PG, Gu ZQ, Skolnick P, Fryer RI..  (1995)  Computer-aided molecular modeling, synthesis, and biological evaluation of 8-(benzyloxy)-2-phenylpyrazolo[4,3-c]quinoline as a novel benzodiazepine receptor agonist ligand.,  38  (6): [PMID:7699711] [10.1021/jm00006a014]

7. PubChem BioAssay data set, 

8. Neaz MM, Muddassar M, Pasha FA, Cho SJ.  (2009)  2D-QSAR of non-benzodiazepines to benzodiazepines receptor (BZR),  18  (2): [10.1007/s00044-008-9111-6]

9. 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]

10. 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]

11. 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]

12. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

13. Beato A, Gori A, Boucherle B, Peuchmaur M, Haudecoeur R..  (2021)  β-Carboline as a Privileged Scaffold for Multitarget Strategies in Alzheimer's Disease Therapy.,  64  (3.0): [PMID:33528252] [10.1021/acs.jmedchem.0c01887]

Source

Source(4):

• Scientific Literature
• PubChem BioAssays
• SARS-CoV-2 Screening Data 2020-21
• Fraunhofer HDAC6