ID: ALA226968

Max Phase: Preclinical

Molecular Formula: C22H28N2O2

Molecular Weight: 352.48

Molecule Type: Small molecule

Representations

Synonyms (1): Tebufenozide
Synonyms from Alternative Forms(1):

Canonical SMILES:  CCc1ccc(C(=O)NN(C(=O)c2cc(C)cc(C)c2)C(C)(C)C)cc1

Standard InChI:  InChI=1S/C22H28N2O2/c1-7-17-8-10-18(11-9-17)20(25)23-24(22(4,5)6)21(26)19-13-15(2)12-16(3)14-19/h8-14H,7H2,1-6H3,(H,23,25)

Standard InChI Key:  QYPNKSZPJQQLRK-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: 352.48

Molecular Weight (Monoisotopic): 352.2151

AlogP: 4.45

#Rotatable Bonds: 3

Polar Surface Area: 49.41

Molecular Species: NEUTRAL

HBA: 2

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 10.13

CX Basic pKa:

CX LogP: 5.35

CX LogD: 5.35

Aromatic Rings: 2

Heavy Atoms: 26

QED Weighted: 0.83

Np Likeness Score: -0.80

References

1. Fujikawa M, Nakao K, Shimizu R, Akamatsu M..  (2007)  QSAR study on permeability of hydrophobic compounds with artificial membranes.,  15  (11): [PMID:17418579] [10.1016/j.bmc.2007.03.040]

2. Mao CH, Wang KL, Wang ZW, Ou XM, Huang RQ, Bi FC, Wang QM..  (2008)  Synthesis and insecticidal evaluation of novel N'-tert-butyl-N'-substitutedbenzoyl-N-5-chloro-6-chromanecarbohydrazide derivatives.,  16  (1): [PMID:17897833] [10.1016/j.bmc.2007.09.018]

3. Esengil H, Chang V, Mich JK, Chen JK..  (2007)  Small-molecule regulation of zebrafish gene expression.,  3  (3): [PMID:17237798] [10.1038/nchembio858]

4. PubChem BioAssay data set, 

5. PubChem BioAssay data set, 

6. Shang J, Sun R, Li Y, Huang R, Bi F, Wang Q..  (2010)  Synthesis and insecticidal evaluation of N-tert-butyl-N'-thio[1-(6-chloro-3-pyridylmethyl)-2-nitroiminoimidazolidine]-N,N'-diacylhydrazines.,  58  (3): [PMID:20041716] [10.1021/jf903642s]

7. Zhao Q, Ou X, Huang Z, Bi F, Huang R, Wang Q..  (2008)  Synthesis and insecticidal activities of novel N-sulfenyl-N'-tert-butyl-N,N'-diacylhydrazines. 3. N-(alkyldithio), n-(aminothio), and N,N-dithio derivatives.,  56  (22): [PMID:18959411] [10.1021/jf802389r]

8. Wang H, Yang Z, Fan Z, Wu Q, Zhang Y, Mi N, Wang S, Zhang Z, Song H, Liu F..  (2011)  Synthesis and insecticidal activity of N-tert-butyl-N,N'-diacylhydrazines containing 1,2,3-thiadiazoles.,  59  (2): [PMID:21166420] [10.1021/jf104004q]

9. Wang Y, Yu R, Zhao X, Chen L, Wu C, Cang T, Wang Q..  (2012)  Susceptibility of adult Trichogramma nubilale (Hymenoptera: Trichogrammatidae) to selected insecticides with different modes of action,  34  [10.1016/j.cropro.2011.12.007]

10. Akamatsu M..  (2011)  Importance of physicochemical properties for the design of new pesticides.,  59  (7): [PMID:20879794] [10.1021/jf102525e]

11. Zhao Q, Shang J, Liu Y, Wang K, Bi F, Huang R, Wang Q..  (2007)  Synthesis and insecticidal activities of novel N-sulfenyl-N'-tert-butyl-N,N'-diacylhydrazines. 1. N-alkoxysulfenate derivatives.,  55  (23): [PMID:17941694] [10.1021/jf072390f]

12. Zhao Q, Shang J, Huang Z, Wang K, Bi F, Huang R, Wang Q..  (2008)  Synthesis and insecticidal activities of novel N-sulfenyl-N'-tert-butyl-N,N'-diacylhydrazines. 2. N-substituted phenoxysulfenate derivatives.,  56  (13): [PMID:18540619] [10.1021/jf800740z]

13. Yokoyama A, Ohtsu K, Iwafune T, Nagai T, Ishihara S, Kobara Y, Horio T, Endo S.  (2009)  A useful new insecticide bioassay using first-instar larvae of a net-spinning caddisfly, Cheumatopsyche brevilineata (Trichoptera: Hydropsychidae),  34  (1): [10.1584/jpestics.G08-26]

14. SAWADA Y, NAKAGAWA H, TSUKAMOTO Y, YANAI T, YOKOI S, YANAGI M, WATANABE T.  (2002)  Synthesis and Insecticidal Activity of 3, 5-Dimethylbenzoyl Moiety Modified Analogues of N-tert-Butyl-N-(4-ethylbenzoyl)-3, 5-dimethylbenzohydrazide,  27  (4): [10.1584/jpestics.27.365]

15. Soin T, De Geyter E, Mosallanejad H, Iga M, Martín D, Ozaki S, Kitsuda S, Harada T, Miyagawa H, Stefanou D, Kotzia G, Efrose R, Labropoulou V, Geelen D, Iatrou K, Nakagawa Y, Janssen CR, Smagghe G, Swevers L..  (2010)  Assessment of species specificity of moulting accelerating compounds in Lepidoptera: comparison of activity between Bombyx mori and Spodoptera littoralis by in vitro reporter and in vivo toxicity assays.,  66  (5): [PMID:20069627] [10.1002/ps.1903]

16. Soin T, Swevers L, Kotzia G, Iatrou K, Janssen CR, Rougé P, Harada T, Nakagawa Y, Smagghe G..  (2010)  Comparison of the activity of non-steroidal ecdysone agonists between dipteran and lepidopteran insects, using cell-based EcR reporter assays.,  66  (11): [PMID:20672340] [10.1002/ps.1998]

17. TAMURA H, TAKADA H, KITO M, MATSUBARA K, OBARA Y, HARA T, KUWANO E.  (1997)  Effect of Insect Hormone Related Compounds on the Growth of Insect Cells,  22  (1): [10.1584/jpestics.22.42]

18. Tohidi-Esfahani D, Lawrence MC, Graham LD, Hannan GN, Simpson AM, Hill RJ..  (2011)  Isoforms of the heteropteran Nezara viridula ecdysone receptor: protein characterisation, RH5992 insecticide binding and homology modelling.,  67  (11): [PMID:21594962] [10.1002/ps.2200]

19. Sun J, Liang P, Gao X..  (2012)  Cross-resistance patterns and fitness in fufenozide-resistant diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).,  68  (2): [PMID:21858910] [10.1002/ps.2258]

20. Bengochea P, Christiaens O, Amor F, Viñuela E, Rougé P, Medina P, Smagghe G..  (2013)  Insect growth regulators as potential insecticides to control olive fruit fly (Bactrocera oleae Rossi): insect toxicity bioassays and molecular docking approach.,  69  (1): [PMID:22730139] [10.1002/ps.3350]

21. PubChem BioAssay data set, 

22. Shirotani N, Togawa M, Ikushiro S, Sakaki T, Harada T, Miyagawa H, Matsui M, Nagahori H, Mikata K, Nishioka K, Hirai N, Akamatsu M..  (2015)  Identification and in silico prediction of metabolites of the model compound, tebufenozide by human CYP3A4 and CYP2C19.,  23  (20): [PMID:26404412] [10.1016/j.bmc.2015.09.019]

23. Miyata K, Nakagawa Y, Kimura Y, Ueda K, Akamatsu M..  (2016)  Structure-activity relationships of dibenzoylhydrazines for the inhibition of P-glycoprotein-mediated quinidine transport.,  24  (14): [PMID:27262425] [10.1016/j.bmc.2016.05.039]

24. 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]

25. 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]

26. Edamatsu H,Yagawa M,Ikushiro S,Sakaki T,Nakagawa Y,Miyagawa H,Akamatsu M.  (2020)  Identification and in silico prediction of metabolites of tebufenozide derivatives by major human cytochrome P450 isoforms.,  28  (9): [PMID:32201191] [10.1016/j.bmc.2020.115429]

Source

Source(3):

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