ID: ALA408867

Max Phase: Preclinical

Molecular Formula: C23H32N2O2

Molecular Weight: 368.52

Molecule Type: Small molecule

Representations

Canonical SMILES:  COc1ccc(CCN2CCN(CCCc3ccccc3)CC2)cc1OC

Standard InChI:  InChI=1S/C23H32N2O2/c1-26-22-11-10-21(19-23(22)27-2)12-14-25-17-15-24(16-18-25)13-6-9-20-7-4-3-5-8-20/h3-5,7-8,10-11,19H,6,9,12-18H2,1-2H3

Standard InChI Key:  UVSWWUWQVAQPJR-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: 368.52

Molecular Weight (Monoisotopic): 368.2464

AlogP: 3.50

#Rotatable Bonds: 9

Polar Surface Area: 24.94

Molecular Species: NEUTRAL

HBA: 4

HBD: 0

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 0

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 8.33

CX LogP: 4.19

CX LogD: 3.22

Aromatic Rings: 2

Heavy Atoms: 27

QED Weighted: 0.68

Np Likeness Score: -0.55

References

1. Nahas RI, Lever JR, Lever SZ..  (2008)  Synthesis and structure-activity relationships of N-(3-phenylpropyl)-N'-benzylpiperazines: Potent ligands for sigma1 and sigma2 receptors.,  16  (2): [PMID:18029187] [10.1016/j.bmc.2007.10.037]

2. Fan KH, Lever JR, Lever SZ..  (2011)  Effect of structural modification in the amine portion of substituted aminobutyl-benzamides as ligands for binding σ1 and σ2 receptors.,  19  (6): [PMID:21376604] [10.1016/j.bmc.2011.02.006]

3. Moussa IA, Banister SD, Manoli M, Doddareddy MR, Cui J, Mach RH, Kassiou M..  (2012)  Exploration of ring size in a series of cyclic vicinal diamines with σ₁ receptor affinity.,  22  (17): [PMID:22850210] [10.1016/j.bmcl.2012.07.026]

4. PubChem BioAssay data set, 

5. Banister SD, Manoli M, Doddareddy MR, Hibbs DE, Kassiou M..  (2012)  A σ(1) receptor pharmacophore derived from a series of N-substituted 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols (AHDs).,  22  (19): [PMID:22959245] [10.1016/j.bmcl.2012.08.046]

6. Li Y, Wang X, Zhang J, Deuther-Conrad W, Xie F, Zhang X, Liu J, Qiao J, Cui M, Steinbach J, Brust P, Liu B, Jia H..  (2013)  Synthesis and evaluation of novel (18)F-labeled spirocyclic piperidine derivatives as σ1 receptor ligands for positron emission tomography imaging.,  56  (9): [PMID:23566245] [10.1021/jm301734g]

7. Valade A, Cross SB, Brown C, Detrait E, Ene D, Gillard M, Guyaux M, Lamberty Y, Maguire M, Namdev N, Provins L, Schwartz E, Vermeiren C.  (2011)  Discovery of novel selective Sigma-1 ligands as cognitive enhancers,  2  (7): [10.1039/C1MD00010A]

8. Xu R, Lord SA, Peterson RM, Fergason-Cantrell EA, Lever JR, Lever SZ..  (2015)  Ether modifications to 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503): effects on binding affinity and selectivity for sigma receptors and monoamine transporters.,  23  (1): [PMID:25468036] [10.1016/j.bmc.2014.11.007]

9. Bautista-Aguilera ÓM, Budni J, Mina F, Medeiros EB, Deuther-Conrad W, Entrena JM, Moraleda I, Iriepa I, López-Muñoz F, Marco-Contelles J..  (2018)  Contilisant, a Tetratarget Small Molecule for Alzheimer's Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile.,  61  (15): [PMID:29969030] [10.1021/acs.jmedchem.8b00848]

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. Ye N,Qin W,Tian S,Xu Q,Wold EA,Zhou J,Zhen XC.  (2020)  Small Molecules Selectively Targeting Sigma-1 Receptor for the Treatment of Neurological Diseases.,  63  (24.0): [PMID:33111525] [10.1021/acs.jmedchem.0c01192]

13. Deuther-Conrad, Winnie, Diez-Iriepa, Daniel, Iriepa, Isabel, Lopez-Munoz, Francisco, Martinez-Grau, Maria Angeles, Gutschow, Michael, Marco-Contelles, Jose.  (2021)  Studies on the affinity of 6-[(n-(cyclo)aminoalkyl)oxy]-4H-chromen-4-ones for sigma 1/2 receptors,  12  (6.0): [PMID:34223165] [10.1039/d1md00105a]

14. 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]

15. Fallica AN, Ciaffaglione V, Modica MN, Pittalà V, Salerno L, Amata E, Marrazzo A, Romeo G, Intagliata S..  (2022)  Structure-activity relationships of mixed σ₁R/σ₂R ligands with antiproliferative and anticancer effects.,  73  [PMID:36202063] [10.1016/j.bmc.2022.117032]

Source

Source(4):

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