6-Methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol hydrochloride

ID: ALA5314363

Chembl Id: CHEMBL5314363

Max Phase: Approved

First Approval: 2001

Molecular Formula: C17H21Cl2NO3

Molecular Weight: 267.33

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Apokinon | Apomine | Apomorphine hcl | Apomorphine hydrochloride | Apomorphine hydrochloride hydrate | Apomorphinum muriaticum | Ixense | Kw-6500 | Taluvian | NSC-11442 | NSC-755875

Trade Names(14): Apo-go | Apo-go pen | Apo-go pfs | Apokyn | Apomorph hcl | Britaject | Dacepton | Diagesil | Diamorph hcl | Diamorph roche | Diamorph,cocaine,chlorpromazine | Diaphine | Kynmobi | Uprima

Canonical SMILES:  CN1CCc2cccc3c2[C@H]1Cc1ccc(O)c(O)c1-3.Cl.Cl.O

Standard InChI:  InChI=1S/C17H17NO2.2ClH.H2O/c1-18-8-7-10-3-2-4-12-15(10)13(18)9-11-5-6-14(19)17(20)16(11)12;;;/h2-6,13,19-20H,7-9H2,1H3;2*1H;1H2/t13-;;;/m1.../s1

Standard InChI Key:  BOQNMOQMVACUOG-BXUUEFRQSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: Yes

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: Yes

Prodrug: No

Calculated Properties

Molecular Weight: 267.33

Molecular Weight (Monoisotopic): 267.1259

AlogP: 2.85

#Rotatable Bonds: ┄

Polar Surface Area: 43.70

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 3

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 9.26

CX Basic pKa: 7.72

CX LogP: 2.88

CX LogD: 2.58

Aromatic Rings: 2

Heavy Atoms: 20

QED Weighted: 0.72

Np Likeness Score: 1.45

References

1. Gao YG, Ram VJ, Campbell A, Kula NS, Baldessarini RJ, Neumeyer JL..  (1990)  Synthesis and structural requirements of N-substituted norapomorphines for affinity and activity at dopamine D-1, D-2, and agonist receptor sites in rat brain.,  33  (1): [PMID:2136919] [10.1021/jm00163a007]

2. Sipos A, Kiss B, Schmidt E, Greiner I, Berényi S..  (2008)  Synthesis and neuropharmacological evaluation of 2-aryl- and alkylapomorphines.,  16  (7): [PMID:18289859] [10.1016/j.bmc.2008.01.057]

3. Lucumi E, Darling C, Jo H, Napper AD, Chandramohanadas R, Fisher N, Shone AE, Jing H, Ward SA, Biagini GA, DeGrado WF, Diamond SL, Greenbaum DC..  (2010)  Discovery of potent small-molecule inhibitors of multidrug-resistant Plasmodium falciparum using a novel miniaturized high-throughput luciferase-based assay.,  54  (9): [PMID:20547797] [10.1128/aac.00431-10]

4. Unpublished dataset, 

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

6. De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP..  (2013)  Structure-based identification of OATP1B1/3 inhibitors.,  83  (6): [PMID:23571415] [10.1124/mol.112.084152]

7. Cannon JG, Suarez-Gutierrez C, Lee T, Long JP, Costall B, Fortune DH, Naylor RJ..  (1979)  Rigid congeners of dopamine based on octahydrobenzo[f]quinoline: peripheral and central effects.,  22  (4): [PMID:571020] [10.1021/jm00190a002]

8. Cannon JG, Hsu FL, Long JP, Flynn JR, Costall B, Naylor RJ..  (1978)  Preparation and biological actions of some symmetrically N,N-disubstituted dopamines.,  21  (3): [PMID:564406] [10.1021/jm00201a002]

9. Cannon JG, Perez Z, Long JP, Rusterholz DB, Flynn JR, Costall B, Fortune DH, Naylor RJ..  (1979)  N-Alkyl derivatives of (+/-)-alpha-methyldopamine.,  22  (8): [PMID:573798] [10.1021/jm00194a003]

10. Ginos JZ, Stevens JM, Nichols DE..  (1979)  Structure--activity relationships of n-substituted dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene analogues: behavioral effects in lesioned and reserpinized mice.,  22  (11): [PMID:574901] [10.1021/jm00197a009]

11. Cannon JG, Hatheway GJ..  (1976)  Centrally acting emetics. 10. Rigid dopamine congeners derived from octahydrobenzo[f]quinoline.,  19  (8): [PMID:184283] [10.1021/jm00230a001]

12. British National Formulary (72nd edition), 

13. Unpublished dataset, 

14. 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]

15. 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]

16. 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]

17. Zhao Y, Guan YY, Zhao F, Yu T, Zhang SJ, Zhang YZ, Duan YC, Zhou XL..  (2022)  Recent strategies targeting Embryonic Ectoderm Development (EED) for cancer therapy: Allosteric inhibitors, PPI inhibitors, and PROTACs.,  231  [PMID:35093670] [10.1016/j.ejmech.2022.114144]

18. European Medicines Agency, 

Source

Source(7):

• Scientific Literature
• Clinical Candidates
• FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book)
• USP Dictionary of USAN and International Drug Names
• British National Formulary
• SARS-CoV-2 Screening Data 2020-21
• European Medicines Agency