6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one

ID: ALA1413

Chembl Id: CHEMBL1413

Cas Number: 29342-05-0

PubChem CID: 2749

Product Number: S64215

Max Phase: Approved

First Approval: 1982

Molecular Formula: C12H17NO2

Molecular Weight: 207.27

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Ciclopirox | Cyclopirox | HOE 296B | HOE-296B | CICLOPIROX|29342-05-0|Loprox|Penlac|HOE 296b|cyclopirox|Ciclopiroxum|Terit|HOE-296b|2(1H)-Pyridinone, 6-cyclohexyl-1-hydroxy-4-methyl-|Ciclopirox gel|Loprox cream|Ciclopiroxum [INN-Latin]|Loprox Gel|6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one|6-Cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridinone|6-cyclohexyl-1-hydroxy-4-methylpyridin-2-one|Ciclodan|CNL8|HOE296b|EINECS 249-577-2|UNII-19W019ZDRJ|Ciclopirox (Penlac)|19W019ZDRJ|CHEBI:453011|Loprox (TN)Show More⌵

Synonyms from Alternative Forms(11): Ciclopirox olamine | Ciclopirox ethanolamine salt (1:1) | Batrafen | Brumixol | Ciclochem | Dafnegin | Micoxolamina | HOE 296 | HOE-296 | NSC-336278 | Mycoster

Trade Names(3): Ciclopirox | Loprox | Penlac

Canonical SMILES:  Cc1cc(C2CCCCC2)n(O)c(=O)c1

Standard InChI:  InChI=1S/C12H17NO2/c1-9-7-11(13(15)12(14)8-9)10-5-3-2-4-6-10/h7-8,10,15H,2-6H2,1H3

Standard InChI Key:  SCKYRAXSEDYPSA-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA1413

   CICLOPIROX

2. Alternative Forms:

   

   ALA1413

   Ciclopirox olamine

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: Yes

First In Class: No

Black Box: No

Chirality: Yes

Availability: Yes

Prodrug: No

Calculated Properties

Molecular Weight: 207.27

Molecular Weight (Monoisotopic): 207.1259

AlogP: 2.44

#Rotatable Bonds: 1

Polar Surface Area: 42.23

Molecular Species: NEUTRAL

HBA: 3

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 3

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 6.84

CX Basic pKa: ┄

CX LogP: 2.22

CX LogD: 1.56

Aromatic Rings: 1

Heavy Atoms: 15

QED Weighted: 0.72

Np Likeness Score: 0.30

References

1. Baker SJ, Zhang YK, Akama T, Lau A, Zhou H, Hernandez V, Mao W, Alley MR, Sanders V, Plattner JJ..  (2006)  Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis.,  49  (15): [PMID:16854048] [10.1021/jm0603724]

2. Gilardoni G, Clericuzio M, Tosi S, Zanoni G, Vidari G..  (2007)  Antifungal acylcyclopentenediones from fruiting bodies of Hygrophorus chrysodon.,  70  (1): [PMID:17253868] [10.1021/np060512c]

3. Zarember KA, Cruz AR, Huang CY, Gallin JI..  (2009)  Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus.,  53  (6): [PMID:19307370] [10.1128/aac.01547-08]

4. Greene N, Fisk L, Naven RT, Note RR, Patel ML, Pelletier DJ..  (2010)  Developing structure-activity relationships for the prediction of hepatotoxicity.,  23  (7): [PMID:20553011] [10.1021/tx1000865]

5. Ekins S, Williams AJ, Xu JJ..  (2010)  A predictive ligand-based Bayesian model for human drug-induced liver injury.,  38  (12): [PMID:20843939] [10.1124/dmd.110.035113]

6. Matthews EJ, Kruhlak NL, Weaver JL, Benz RD, Contrera JF..  (2004)  Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.,  1  (4): [PMID:16472241] [10.2174/1570163043334794]

7. Unpublished dataset, 

8. Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program. DrugMatrix in vitro pharmacology data, 

9. Liu Z, Shi Q, Ding D, Kelly R, Fang H, Tong W..  (2011)  Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).,  7  (12): [PMID:22194678] [10.1371/journal.pcbi.1002310]

10. Schüffler A, Wollinsky B, Anke T, Liermann JC, Opatz T..  (2012)  Isolactarane and sterpurane sesquiterpenoids from the basidiomycete Phlebia uda.,  75  (7): [PMID:22746380] [10.1021/np3000552]

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

12. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM..  (2013)  Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling.,  56  (3): [PMID:23241029] [10.1021/jm301302s]

13. Röhrig UF, Majjigapu SR, Chambon M, Bron S, Pilotte L, Colau D, Van den Eynde BJ, Turcatti G, Vogel P, Zoete V, Michielin O..  (2014)  Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.,  84  [PMID:25036789] [10.1016/j.ejmech.2014.06.078]

14. Liu Z, Yao Y, Kogiso M, Zheng B, Deng L, Qiu JJ, Dong S, Lv H, Gallo JM, Li XN, Song Y..  (2014)  Inhibition of cancer-associated mutant isocitrate dehydrogenases: synthesis, structure-activity relationship, and selective antitumor activity.,  57  (20): [PMID:25271760] [10.1021/jm500660f]

15.  (2014)  Agents and methods for treating ischemic and other diseases, 

16. WHO Anatomical Therapeutic Chemical Classification, 

17. Singh S, Goo JI, Noh H, Lee SJ, Kim MW, Park H, Jalani HB, Lee K, Kim C, Kim WK, Ju C, Choi Y..  (2017)  Discovery of a novel series of N-hydroxypyridone derivatives protecting astrocytes against hydrogen peroxide-induced toxicity via improved mitochondrial functionality.,  25  (4): [PMID:28089588] [10.1016/j.bmc.2016.12.052]

18. Morgan RE, van Staden CJ, Chen Y, Kalyanaraman N, Kalanzi J, Dunn RT, Afshari CA, Hamadeh HK..  (2013)  A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.,  136  (1): [PMID:23956101] [10.1093/toxsci/kft176]

19. Unpublished dataset, 

20. 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]

21. Hu L, Feng H, Zhang H, Yu S, Zhao Q, Wang W, Bao F, Ding X, Hu J, Wang M, Xu Y, Wu Z, Li X, Tang Y, Mao F, Chen X, Zhang H, Li J..  (2020)  Development of Novel N-hydroxypyridone Derivatives as Potential Anti-Ischemic Stroke Agents.,  63  (3): [PMID:31910018] [10.1021/acs.jmedchem.9b01338]

22. Jiang Z, You Q, Zhang X..  (2019)  Medicinal chemistry of metal chelating fragments in metalloenzyme active sites: A perspective.,  165  [PMID:30684796] [10.1016/j.ejmech.2019.01.018]

23. 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]

24. 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]

25. Johannes Zuegg, Alysha Elliott, Maite Amado, Emma Cowie, Ali Hinton, Geraldine Kaeslin, Angela Kavanagh, Anne Kunert, Gabriell Lowe, Soumya Ramu, Janet Reid, Robin Trauer, Mathilde Desselle, Ruth Neale, Karl Hansford, Mark Blascovich, Matthew Cooper. CO-ADD screening of MMV (CH) - Pandemic Response Box,  [10.6019/CHEMBL4513161]

26. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

27. 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]

28. Choi JW, Lee KT, Kim S, Lee YR, Kim HJ, Seo KJ, Lee MH, Yeon SK, Jang BK, Park SJ, Kim HJ, Park JH, Kim D, Lee DG, Cheong E, Lee JS, Bahn YS, Park KD..  (2021)  Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection.,  64  (21.0): [PMID:34662122] [10.1021/acs.jmedchem.1c01299]

29. Zangi M, Donald KA, Casals AG, Franson AD, Yu AJ, Marker EM, Woodson ME, Campbell SD, Mottaleb MA, Narayana Hajay Kumar TV, Reddy MS, Raghava Reddy LV, Sadhukhan SK, Griggs DW, Morrison LA, Meyers MJ..  (2022)  Synthetic derivatives of the antifungal drug ciclopirox are active against herpes simplex virus 2.,  238  [PMID:35635945] [10.1016/j.ejmech.2022.114443]

30. Wu Q, Young B, Wang Y, Davidoff AM, Rankovic Z, Yang J..  (2022)  Recent Advances with KDM4 Inhibitors and Potential Applications.,  65  (14.0): [PMID:35838529] [10.1021/acs.jmedchem.2c00680]

31. Sutherland JJ, Yonchev D, Fekete A, Urban L..  (2023)  A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs.,  14  (1): [PMID:37468498] [10.1038/s41467-023-40064-9]

Source

Source(11):

• Scientific Literature
• Clinical Candidates
• FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book)
• USP Dictionary of USAN and International Drug Names
• DrugMatrix
• Patent Bioactivity Data
• CO-ADD antimicrobial screening data
• WHO Anatomical Therapeutic Chemical Classification
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6