ID: ALA107400

Max Phase: Phase

Molecular Formula: C20H24O4

Molecular Weight: 328.41

Molecule Type: Small molecule

Representations

Synonyms (3): Sobetirome | GC-1 | QRX-431
Synonyms from Alternative Forms(3):

Canonical SMILES:  Cc1cc(OCC(=O)O)cc(C)c1Cc1ccc(O)c(C(C)C)c1

Standard InChI:  InChI=1S/C20H24O4/c1-12(2)17-9-15(5-6-19(17)21)10-18-13(3)7-16(8-14(18)4)24-11-20(22)23/h5-9,12,21H,10-11H2,1-4H3,(H,22,23)

Standard InChI Key:  QNAZTOHXCZPOSA-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: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 328.41

Molecular Weight (Monoisotopic): 328.1675

AlogP: 4.19

#Rotatable Bonds: 6

Polar Surface Area: 66.76

Molecular Species: ACID

HBA: 3

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 3.93

CX Basic pKa:

CX LogP: 5.35

CX LogD: 2.15

Aromatic Rings: 2

Heavy Atoms: 24

QED Weighted: 0.83

Np Likeness Score: 0.11

References

1. Yoshihara HA, Apriletti JW, Baxter JD, Scanlan TS..  (2003)  Structural determinants of selective thyromimetics.,  46  (14): [PMID:12825953] [10.1021/jm0301181]

2. Nguyen NH, Apriletti JW, Cunha Lima ST, Webb P, Baxter JD, Scanlan TS..  (2002)  Rational design and synthesis of a novel thyroid hormone antagonist that blocks coactivator recruitment.,  45  (15): [PMID:12109914] [10.1021/jm0201013]

3. Boyer SH, Jiang H, Jacintho JD, Reddy MV, Li H, Li W, Godwin JL, Schulz WG, Cable EE, Hou J, Wu R, Fujitaki JM, Hecker SJ, Erion MD..  (2008)  Synthesis and biological evaluation of a series of liver-selective phosphonic acid thyroid hormone receptor agonists and their prodrugs.,  51  (22): [PMID:18975928] [10.1021/jm800824d]

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

5. Joharapurkar AA, Dhote VV, Jain MR..  (2012)  Selective thyromimetics using receptor and tissue selectivity approaches: prospects for dyslipidemia.,  55  (12): [PMID:22512468] [10.1021/jm2004706]

6. Takahashi N, Maeda K, Asano Y, Watanabe N..  (2014)  Synthesis and pharmacological characterization of 1-benzyl-4-aminoindole-based thyroid hormone receptor β agonists.,  22  (1): [PMID:24290064] [10.1016/j.bmc.2013.11.001]

7. Kelly MJ, Pietranico-Cole S, Larigan JD, Haynes NE, Reynolds CH, Scott N, Vermeulen J, Dvorozniak M, Conde-Knape K, Huang KS, So SS, Thakkar K, Qian Y, Banner B, Mennona F, Danzi S, Klein I, Taub R, Tilley J..  (2014)  Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a Highly Selective Thyroid Hormone Receptor β agonist in clinical trials for the treatment of dyslipidemia.,  57  (10): [PMID:24712661] [10.1021/jm4019299]

8. Ferrara SJ, Meinig JM, Placzek AT, Banerji T, McTigue P, Hartley MD, Sanford-Crane HS, Banerji T, Bourdette D, Scanlan TS..  (2017)  Ester-to-amide rearrangement of ethanolamine-derived prodrugs of sobetirome with increased blood-brain barrier penetration.,  25  (10): [PMID:28385597] [10.1016/j.bmc.2017.03.047]

9. Unpublished dataset, 

10. 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]

11. Meinig JM, Ferrara SJ, Banerji T, Banerji T, Sanford-Crane HS, Bourdette D, Scanlan TS..  (2019)  Structure-Activity Relationships of Central Nervous System Penetration by Fatty Acid Amide Hydrolase (FAAH)-Targeted Thyromimetic Prodrugs.,  10  (1): [PMID:30655956] [10.1021/acsmedchemlett.8b00501]

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. 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]

14. 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]

15. 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]

16. Placzek AT,Ferrara SJ,Hartley MD,Sanford-Crane HS,Meinig JM,Scanlan TS.  (2016)  Sobetirome prodrug esters with enhanced blood-brain barrier permeability.,  24  (22.0): [PMID:27707627] [10.1016/j.bmc.2016.09.038]

17.  (2021)  EUbOPEN Chemogenomics Library wave 1,  [10.6019/CHEMBL4689842]

18. 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]

19. EUbOPEN.  (2022)  EUbOPEN Chemogenomics Library wave 2 - DSF,  [10.6019/CHEMBL5060014]

20. Come JH, Senter TJ, Clark MP, Court JJ, Gale-Day Z, Gu W, Krueger E, Liang J, Morris M, Nanthakumar S, O'Dowd H, Maltais F, Iyer G, Andreassi J, Boucher C, Considine T, Moody CS, Taylor W, Mohanty AK, Huang Y, Zuccola H, Coll J, Bonanno KC, Gagnon KJ, Gan L, Lu F, Gao H, Chakilam A, Engtrakul J, Song B, Crawford D, Doyle E, Kramer T, Vought B, Phillips J, Kemper R, Sanders M, Swett R, Furey B, Winquist R, Bunnage ME, Jackson KL, Charifson PS, Magavi SS..  (2021)  Discovery and Optimization of Pyrazole Amides as Inhibitors of ELOVL1.,  64  (24.0): [PMID:34748351] [10.1021/acs.jmedchem.1c00944]

Source

Source(6):

• Scientific Literature
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names
• SARS-CoV-2 Screening Data 2020-21
• EUbOPEN Chemogenomic Library
• Fraunhofer HDAC6