2-Amino-4-(4-methoxyphenyl)-7-(naphthalene-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile

ID: ALA474133

Chembl Id: CHEMBL474133

Max Phase: Preclinical

Molecular Formula: C27H22N2O3

Molecular Weight: 422.48

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COc1ccc(C2C(C#N)=C(N)OC3=C2C(=O)CC(c2cccc4ccccc24)C3)cc1

Standard InChI:  InChI=1S/C27H22N2O3/c1-31-19-11-9-17(10-12-19)25-22(15-28)27(29)32-24-14-18(13-23(30)26(24)25)21-8-4-6-16-5-2-3-7-20(16)21/h2-12,18,25H,13-14,29H2,1H3

Standard InChI Key:  YBMGNDPBARCLFT-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA474133

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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

Calculated Properties

Molecular Weight: 422.48

Molecular Weight (Monoisotopic): 422.1630

AlogP: 5.06

#Rotatable Bonds: 3

Polar Surface Area: 85.34

Molecular Species: NEUTRAL

HBA: 5

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 1.94

CX LogP: 4.12

CX LogD: 4.12

Aromatic Rings: 3

Heavy Atoms: 32

QED Weighted: 0.64

Np Likeness Score: -0.73

References

1. Jensen AA, Erichsen MN, Nielsen CW, Stensbøl TB, Kehler J, Bunch L..  (2009)  Discovery of the first selective inhibitor of excitatory amino acid transporter subtype 1.,  52  (4): [PMID:19161278] [10.1021/jm8013458]

2. Erichsen MN, Huynh TH, Abrahamsen B, Bastlund JF, Bundgaard C, Monrad O, Bekker-Jensen A, Nielsen CW, Frydenvang K, Jensen AA, Bunch L..  (2010)  Structure-activity relationship study of first selective inhibitor of excitatory amino acid transporter subtype 1: 2-Amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101).,  53  (19): [PMID:20857912] [10.1021/jm1009154]

3. Huynh TH, Shim I, Bohr H, Abrahamsen B, Nielsen B, Jensen AA, Bunch L..  (2012)  Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio Hartree-Fock calculations.,  55  (11): [PMID:22594609] [10.1021/jm300345z]

4. Wang WW, Gallo L, Jadhav A, Hawkins R, Parker CG..  (2020)  The Druggability of Solute Carriers.,  63  (8): [PMID:31774679] [10.1021/acs.jmedchem.9b01237]

5. 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]

6. 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]

7. Hubert J. Sijben; Laura Dall' Acqua; Rongfang Liu; Abigail Jarret; Eirini Christodoulaki; Svenja Onstein; Gernot Wolf; Simone J. Verburgt; Sylvia E. Le Dévédec; Tabea Wiedmer; Giulio Superti-Furga; Adriaan P. Ijzerman; Laura H. Heitman.  (2022)  Impedance-Based Phenotypic Readout of Transporter Function: A Case for Glutamate Transporters,  13  [PMID:35677430] [10.3389/fphar.2022.872335]

Source

Source(3):

• Scientific Literature
• SARS-CoV-2 Screening Data 2020-21
• RESOLUTE - Research Empowerment on Solute Carriers