5-{4-[4-(5-Cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-benzofuran-2-carboxylic acid amide

ID: ALA439849

Cas Number: 163521-12-8

PubChem CID: 6918314

Product Number: V422008, Order Now?

Max Phase: Approved

First Approval: 2011

Molecular Formula: C26H27N5O2

Molecular Weight: 441.54

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Vilazodone | EMD 515259 | EMD-515259 | EMD-68-843 | Vilazodone|163521-12-8|5-(4-(4-(5-Cyano-1H-indol-3-yl)butyl)piperazin-1-yl)benzofuran-2-carboxamide|EMD 515259|vilazodona|vilazodonum|UNII-S239O2OOV3|EMD-515259|EMD-68-843|S239O2OOV3|CHEBI:70707|HSDB 8197|5-{4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl}-1-benzofuran-2-carboxamide|5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxamide|CHEMBL439849|5-(4-(4-(5-Cyanoindol-3-yl)butyl)-1-piperazinyl)-2-benzofurancarboxamiShow More⌵

Synonyms from Alternative Forms(7): Vilazodone hydrochloride | Vilazodone hcl | EMD 68 843 | EMD-68843 | SB-659746-A | SB659746-A | Viibryd

Canonical SMILES:  N#Cc1ccc2[nH]cc(CCCCN3CCN(c4ccc5oc(C(N)=O)cc5c4)CC3)c2c1

Standard InChI:  InChI=1S/C26H27N5O2/c27-16-18-4-6-23-22(13-18)19(17-29-23)3-1-2-8-30-9-11-31(12-10-30)21-5-7-24-20(14-21)15-25(33-24)26(28)32/h4-7,13-15,17,29H,1-3,8-12H2,(H2,28,32)

Standard InChI Key:  SGEGOXDYSFKCPT-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 33 37  0  0  0  0  0  0  0  0999 V2000
    5.8364    0.6713    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8364   -0.1537    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5509   -0.5662    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2653   -0.1537    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2653    0.6713    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5509    1.0838    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7224   -1.3732    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5429   -1.4594    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.8784   -0.7057    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.9554   -2.1739    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7804   -2.1739    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.5429   -2.8883    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.1219    1.0838    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.1219    1.9088    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4075    2.3213    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6930    1.9088    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.6930    1.0838    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4075    0.6713    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9785    2.3213    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2640    1.9088    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5496    2.3213    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8351    1.9088    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1206    2.3213    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0344    3.1418    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7726    3.3133    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1851    2.5989    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6330    1.9858    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9920    2.4273    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2470    1.6427    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6949    1.0296    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8880    1.2011    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1125    0.3208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5292   -0.3917    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  1  1  0
  3  7  1  0
  7  8  2  0
  8  9  1  0
  9  4  1  0
  8 10  1  0
 10 11  1  0
 10 12  2  0
  1 13  1  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 13  1  0
 16 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 23 24  2  0
 24 25  1  0
 25 26  1  0
 26 27  2  0
 27 23  1  0
 26 28  1  0
 28 29  2  0
 29 30  1  0
 30 31  2  0
 31 27  1  0
  1  2  2  0
 30 32  1  0
  2  3  1  0
 32 33  3  0
M  END

Alternative Forms

1. Parent:

   

   ALA439849

   Vilazodone

2. Alternative Forms:

   

   ALA439849

   Vilazodone HCl

Molecule Features

Natural Product: Yes

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: Yes

Chirality: Yes

Availability: Yes

Prodrug: No

Calculated Properties

Molecular Weight: 441.54

Molecular Weight (Monoisotopic): 441.2165

AlogP: 4.03

#Rotatable Bonds: 7

Polar Surface Area: 102.29

Molecular Species: BASE

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 8.60

CX LogP: 3.72

CX LogD: 2.49

Aromatic Rings: 4

Heavy Atoms: 33

QED Weighted: 0.42

Np Likeness Score: -1.20

References

1. Heinrich T, Böttcher H, Gericke R, Bartoszyk GD, Anzali S, Seyfried CA, Greiner HE, Van Amsterdam C..  (2004)  Synthesis and structure--activity relationship in a class of indolebutylpiperazines as dual 5-HT(1A) receptor agonists and serotonin reuptake inhibitors.,  47  (19): [PMID:15341484] [10.1021/jm040793q]

2. Zhu XY, Etukala JR, Eyunni SV, Setola V, Roth BL, Ablordeppey SY..  (2012)  Benzothiazoles as probes for the 5HT1A receptor and the serotonin transporter (SERT): a search for new dual-acting agents as potential antidepressants.,  53  [PMID:22520153] [10.1016/j.ejmech.2012.03.042]

3. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

4. WHO Anatomical Therapeutic Chemical Classification, 

5. Liu W, Wang H, Li X, Xu Y, Zhang J, Wang W, Gong Q, Qiu X, Zhu J, Mao F, Zhang H, Li J..  (2018)  Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment.,  26  (12): [PMID:29729987] [10.1016/j.bmc.2018.04.037]

6. Unpublished dataset, 

7. Katie Heiser, Peter F. McLean, Chadwick T. Davis, Ben Fogelson, Hannah B. Gordon, Pamela Jacobson, Brett Hurst, Ben Miller, Ronald W. Alfa, Berton A. Earnshaw, Mason L. Victors, Yolanda T. Chong, Imran S. Haque, Adeline S. Low, Christopher C. Gibson.  (2020)  Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2,  [10.1101/2020.04.21.054387]

8. Wróbel MZ, Chodkowski A, Herold F, Marciniak M, Dawidowski M, Siwek A, Starowicz G, Stachowicz K, Szewczyk B, Nowak G, Belka M, Bączek T, Satała G, Bojarski AJ, Turło J..  (2019)  Synthesis and biological evaluation of new multi-target 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with potential antidepressant effect.,  183  [PMID:31586817] [10.1016/j.ejmech.2019.111736]

9. Mishra P, Kumar A, Panda G..  (2019)  Anti-cholinesterase hybrids as multi-target-directed ligands against Alzheimer's disease (1998-2018).,  27  (6): [PMID:30744931] [10.1016/j.bmc.2019.01.025]

10. Meanwell NA..  (2018)  Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design.,  61  (14): [PMID:29400967] [10.1021/acs.jmedchem.7b01788]

11. Gu ZS, Wang WT, Qian H, Zhou AN, Sun HB, Zhang QW, Li JQ..  (2019)  Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7.,  29  (23): [PMID:31627993] [10.1016/j.bmcl.2019.126703]

12. 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]

13. 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]

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. Xu T, Xue Y, Lu J, Jin C..  (2021)  Synthesis and biological evaluation of 1-(4-(piperazin-1-yl)phenyl)pyridin-2(1H)-one derivatives as potential SSRIs.,  223  [PMID:34182358] [10.1016/j.ejmech.2021.113644]

16. Li X, Li J, Huang Y, Gong Q, Fu Y, Xu Y, Huang J, You H, Zhang D, Zhang D, Mao F, Zhu J, Wang H, Zhang H, Li J..  (2022)  The novel therapeutic strategy of vilazodone-donepezil chimeras as potent triple-target ligands for the potential treatment of Alzheimer's disease with comorbid depression.,  229  [PMID:34922191] [10.1016/j.ejmech.2021.114045]

17. Zhang C, Wang L, Xu Y, Huang Y, Huang J, Zhu J, Wang W, Li W, Sun A, Li X, Zhang H, Li J..  (2022)  Discovery of novel dual RAGE/SERT inhibitors for the potential treatment of the comorbidity of Alzheimer's disease and depression.,  236  [PMID:35430560] [10.1016/j.ejmech.2022.114347]

18. Yuan RX, Jiang KY, Wu JW, Zhang ZX, Li MS, Li JQ, Ni F..  (2022)  Synthesis and antidepressant activity of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives selectively targeting SSRI/5-HT_1A.,  76  [PMID:36202190] [10.1016/j.bmcl.2022.129006]

19. Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL..  (2019)  Mapping human microbiome drug metabolism by gut bacteria and their genes.,  570  (7762): [PMID:31158845] [10.1038/s41586-019-1291-3]

20. Institute for Molecular Medicine Finland - High Throughput Biomedicine Unit.  (2023)  ECBD screening data for assay EOS300108,  [10.6019/EOS300108]

Source

Source(8):

• Scientific Literature
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names
• WHO Anatomical Therapeutic Chemical Classification
• SARS-CoV-2 Screening Data 2020-21
• Fraunhofer HDAC6
• EU-OPENSCREEN dataset
• Zimmerman Lab Biotransformation data Dec 2023