ID: ALA38686

Max Phase: Preclinical

Molecular Formula: C22H25NO2

Molecular Weight: 335.45

Molecule Type: Small molecule

Representations

Synonyms (1): SKF-89976
Synonyms from Alternative Forms(1):

Canonical SMILES:  O=C(O)C1CCCN(CCC=C(c2ccccc2)c2ccccc2)C1

Standard InChI:  InChI=1S/C22H25NO2/c24-22(25)20-13-7-15-23(17-20)16-8-14-21(18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-6,9-12,14,20H,7-8,13,15-17H2,(H,24,25)

Standard InChI Key:  TXQKSMSLZVKQBI-UHFFFAOYSA-N

Molecule Features

Natural Product: Yes

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: 335.45

Molecular Weight (Monoisotopic): 335.1885

AlogP: 4.31

#Rotatable Bonds: 6

Polar Surface Area: 40.54

Molecular Species: ZWITTERION

HBA: 2

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 3

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 3.42

CX Basic pKa: 9.79

CX LogP: 1.74

CX LogD: 1.74

Aromatic Rings: 2

Heavy Atoms: 25

QED Weighted: 0.86

Np Likeness Score: -0.26

References

1. Murali Dhar T, Nakanishi H, Borden LA, Gluchowski C.  (1996)  On the bioactive conformation of the gaba uptake inhibitor SK&F 89976-A,  6  (13): [10.1016/S0960-894X(96)00268-5]

2. N'Goka V, Schlewer G, Linget JM, Chambon JP, Wermuth CG..  (1991)  GABA-uptake inhibitors: construction of a general pharmacophore model and successful prediction of a new representative.,  34  (8): [PMID:1831508] [10.1021/jm00112a032]

3. Pavia MR, Lobbestael SJ, Nugiel D, Mayhugh DR, Gregor VE, Taylor CP, Schwarz RD, Brahce L, Vartanian MG..  (1992)  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake.,  35  (22): [PMID:1433224] [10.1021/jm00100a032]

4. Ali FE, Bondinell WE, Dandridge PA, Frazee JS, Garvey E, Girard GR, Kaiser C, Ku TW, Lafferty JJ, Moonsammy GI..  (1985)  Orally active and potent inhibitors of gamma-aminobutyric acid uptake.,  28  (5): [PMID:2985785] [10.1021/jm50001a020]

5. Kehler J, Stensbøl TB, Krogsgaard-Larsen P..  (1999)  Piperidinyl-3-phosphinic acids as novel uptake inhibitors of the neurotransmitter gamma-aminobutyric acid (GABA).,  9  (6): [PMID:10206541] [10.1016/s0960-894x(99)00083-9]

6. Kragler A, Höfner G, Wanner KT..  (2008)  Synthesis and biological evaluation of aminomethylphenol derivatives as inhibitors of the murine GABA transporters mGAT1-mGAT4.,  43  (11): [PMID:18395300] [10.1016/j.ejmech.2008.01.005]

7. Faust MR, Höfner G, Pabel J, Wanner KT..  (2010)  Azetidine derivatives as novel gamma-aminobutyric acid uptake inhibitors: synthesis, biological evaluation, and structure-activity relationship.,  45  (6): [PMID:20219271] [10.1016/j.ejmech.2010.02.029]

8. PubChem BioAssay data set, 

9. PubChem BioAssay data set, 

10. Sindelar M, Lutz TA, Petrera M, Wanner KT..  (2013)  Focused pseudostatic hydrazone libraries screened by mass spectrometry binding assay: optimizing affinities toward γ-aminobutyric acid transporter 1.,  56  (3): [PMID:23336362] [10.1021/jm301800j]

11. Sitka I, Allmendinger L, Fülep G, Höfner G, Wanner KT..  (2013)  Synthesis of N-substituted acyclic β-amino acids and their investigation as GABA uptake inhibitors.,  65  [PMID:23770450] [10.1016/j.ejmech.2013.04.063]

12. PubChem BioAssay data set, 

13. Hellenbrand T, Höfner G, Wein T, Wanner KT..  (2016)  Synthesis of 4-substituted nipecotic acid derivatives and their evaluation as potential GABA uptake inhibitors.,  24  (9): [PMID:27039250] [10.1016/j.bmc.2016.03.038]

14. Kern F, Wanner KT..  (2019)  Screening oxime libraries by means of mass spectrometry (MS) binding assays: Identification of new highly potent inhibitors to optimized inhibitors γ-aminobutyric acid transporter 1.,  27  (7): [PMID:30777661] [10.1016/j.bmc.2019.02.015]

15. 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]

16. 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]

17. 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]

Source

Source(4):

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