ID: ALA761

Max Phase: Approved

First Approval: 1971

Molecular Formula: C14H14N2

Molecular Weight: 210.28

Molecule Type: Small molecule

Representations

Synonyms (3): Nafazair | Nafazolin | Naphazoline
Synonyms from Alternative Forms(3):

Canonical SMILES:  c1ccc2c(CC3=NCCN3)cccc2c1

Standard InChI:  InChI=1S/C14H14N2/c1-2-7-13-11(4-1)5-3-6-12(13)10-14-15-8-9-16-14/h1-7H,8-10H2,(H,15,16)

Standard InChI Key:  CNIIGCLFLJGOGP-UHFFFAOYSA-N

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

Properties

Molecular Weight: 210.28

Molecular Weight (Monoisotopic): 210.1157

AlogP: 2.38

#Rotatable Bonds: 2

Polar Surface Area: 24.39

Molecular Species: BASE

HBA: 2

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 2

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 10.19

CX LogP: 2.19

CX LogD: -0.07

Aromatic Rings: 2

Heavy Atoms: 16

QED Weighted: 0.81

Np Likeness Score: -0.35

References

1. Timmermans PB, van Zwieten PA..  (1982)  alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs.,  25  (12): [PMID:6296387] [10.1021/jm00354a001]

2. Andrews PR, Craik DJ, Martin JL..  (1984)  Functional group contributions to drug-receptor interactions.,  27  (12): [PMID:6094812] [10.1021/jm00378a021]

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4. Timmermans PB, de Jonge A, Thoolen MJ, Wilffert B, Batink H, van Zwieten PA..  (1984)  Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists.,  27  (4): [PMID:6142954] [10.1021/jm00370a011]

5. Timmermans PB, de Jonge A, van Meel JC, Slothorst-Grisdijk FP, Lam E, van Zwieten PA..  (1981)  Characterization of alpha-adrenoceptor populations. Quantitative relationships between cardiovascular effects initiated at central and peripheral alpha-adrenoceptors.,  24  (5): [PMID:6264080] [10.1021/jm00137a006]

6. Navas F, Bishop MJ, Garrison DT, Hodson SJ, Speake JD, Bigham EC, Drewry DH, Saussy DL, Liacos JH, Irving PE, Gobel MJ..  (2002)  2-(anilinomethyl)imidazolines as alpha1A adrenergic receptor agonists: 2'-heteroaryl and 2'-oxime ether series.,  12  (4): [PMID:11844675] [10.1016/s0960-894x(01)00822-8]

7. Nikolic K, Filipic S, Agbaba D..  (2008)  QSAR study of imidazoline antihypertensive drugs.,  16  (15): [PMID:18621536] [10.1016/j.bmc.2008.06.051]

8. PubChem BioAssay data set, 

9. PubChem BioAssay data set, 

10. 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]

11. Nicolotti O, Carotti A, Carrieri A, Pigini M, Gentili F, Brasili L, Giannella M, Quaglia W, Piergentili A, Bousquet P, Dontenwill M.  (2004)  Alpha2-Adrenergic Receptors in Intestinal Epithelial Cells: Mechanisms of Signaling, Role, and Regulation,  13  (3): [10.1007/s00044-004-0023-9]

12. de Jong AP, van Dam H..  (1979)  Ultraviolet photoelectron spectroscopy of cyclic amidines. 1. Electronic structure of some alpha-adrenergic benzylimidazolines.,  22  (11): [PMID:42798] [10.1021/jm00197a003]

13. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]

14. Szőllősi E, Bobok A, Kiss L, Vass M, Kurkó D, Kolok S, Visegrády A, Keserű GM..  (2015)  Cell-based and virtual fragment screening for adrenergic α2C receptor agonists.,  23  (14): [PMID:25648685] [10.1016/j.bmc.2015.01.013]

15. WHO Anatomical Therapeutic Chemical Classification, 

16. Warner DJ, Chen H, Cantin LD, Kenna JG, Stahl S, Walker CL, Noeske T..  (2012)  Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.,  40  (12): [PMID:22961681] [10.1124/dmd.112.047068]

17. Unpublished dataset, 

18. 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]

19. 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]

20. 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]

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

22. 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]

23. 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(8):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• AstraZeneca Deposited Data
• WHO Anatomical Therapeutic Chemical Classification
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6