2-[(2,8-Bis-trifluoromethyl-quinolin-4-yl)-hydroxy-methyl]-piperidinium chloride

ID: ALA535650

Cas Number: 51773-92-3

PubChem CID: 441362

Max Phase: Approved

First Approval: 1989

Molecular Formula: C17H17ClF6N2O

Molecular Weight: 378.32

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Loriam | Mefloquine hcl | Mefloquine hydrochloride | Mefloquini hydrochloridum | NSC-157387 | RO 21-5998/001 | RO-21-5998 | RO-215998001 | WR-142490 | Mefloquine hydrochloride|51773-92-3|Mefloquinehydrochloride|TCMDC-124288|SR-05000001820|Ro-21-5998|Prestwick_538|Mefloquini hydrochloridum|WR-142490|Mephaquin; Racemic mefloquine; Ro 21-5998; WR 142490|SCHEMBL41095|MLS002154206|CHEMBL535650|HMS1568I14|Pharmakon1600-01503070|BCP01049|NSC758233|AB07167|AB45053|CCG-213099|SMR001233492|FT-0640025|EN30Show More⌵

Trade Names(3): Fansimef | Lariam | Mefloquine hydrochloride

Canonical SMILES:  Cl.OC(c1cc(C(F)(F)F)nc2c(C(F)(F)F)cccc12)C1CCCCN1

Standard InChI:  InChI=1S/C17H16F6N2O.ClH/c18-16(19,20)11-5-3-4-9-10(15(26)12-6-1-2-7-24-12)8-13(17(21,22)23)25-14(9)11;/h3-5,8,12,15,24,26H,1-2,6-7H2;1H

Standard InChI Key:  WESWYMRNZNDGBX-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 27 28  0  0  0  0  0  0  0  0999 V2000
    0.4025   -5.9380    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    0.4357   -1.8175    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1370   -1.4109    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2821   -1.4109    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1370   -3.0499    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2821   -0.5893    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8548   -1.8175    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5769   -1.3984    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4357   -2.6433    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8548   -2.6391    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1370   -3.8508    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8548   -5.0915    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.8548   -4.2616    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5395   -0.5893    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1037   -0.5893    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2821    0.2323    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    3.2989   -1.0001    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.9794   -2.1204    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.1702   -0.6847    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9959   -1.8299    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4150   -4.2740    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2821   -3.0499    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5561   -5.4940    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9959   -2.6391    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5561   -3.8508    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2782   -5.0915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2782   -4.2740    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  3  2  1  0
  4  2  1  0
  5  9  1  0
  6  4  1  0
  7  3  2  0
  8  7  1  0
  9  2  2  0
 10  5  2  0
 11  5  1  0
 12 13  1  0
 13 11  1  0
 14  6  1  0
 15  6  1  0
 16  6  1  0
 17  8  1  0
 18  8  1  0
 19  8  1  0
 20  4  2  0
 21 11  1  0
 22  9  1  0
 23 12  1  0
 24 22  2  0
 25 13  1  0
 26 27  1  0
 27 25  1  0
 20 24  1  0
  7 10  1  0
 23 26  1  0
M  END

Molecule Features

Natural Product: No

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: Yes

Chirality: No

Availability: Yes

Prodrug: No

Calculated Properties

Molecular Weight: 378.32

Molecular Weight (Monoisotopic): 378.1167

AlogP: 4.45

#Rotatable Bonds: 2

Polar Surface Area: 45.15

Molecular Species: BASE

HBA: 3

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 3

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 13.79

CX Basic pKa: 9.46

CX LogP: 4.11

CX LogD: 2.07

Aromatic Rings: 2

Heavy Atoms: 26

QED Weighted: 0.76

Np Likeness Score: 0.03

References

1. Keserü GM..  (2003)  Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods.,  13  (16): [PMID:12873512] [10.1016/s0960-894x(03)00492-x]

2. Adam S.  (1992)  Nor-mefloquine: Stereospecific synthesis and biological properties,  2  (1): [10.1016/S0960-894X(00)80654-X]

3. Bacon DJ, Latour C, Lucas C, Colina O, Ringwald P, Picot S..  (2007)  Comparison of a SYBR green I-based assay with a histidine-rich protein II enzyme-linked immunosorbent assay for in vitro antimalarial drug efficacy testing and application to clinical isolates.,  51  (4): [PMID:17220424] [10.1128/aac.01313-06]

4. Rosenthal AS, Chen X, Liu JO, West DC, Hergenrother PJ, Shapiro TA, Posner GH..  (2009)  Malaria-infected mice are cured by a single oral dose of new dimeric trioxane sulfones which are also selectively and powerfully cytotoxic to cancer cells.,  52  (4): [PMID:19186946] [10.1021/jm801484v]

5. PubChem BioAssay data set, 

6. Preechapornkul P, Imwong M, Chotivanich K, Pongtavornpinyo W, Dondorp AM, Day NP, White NJ, Pukrittayakamee S..  (2009)  Plasmodium falciparum pfmdr1 amplification, mefloquine resistance, and parasite fitness.,  53  (4): [PMID:19164150] [10.1128/aac.00241-08]

7. Unpublished dataset, 

8. Isaka M, Chinthanom P, Sappan M, Chanthaket R, Luangsa-ard JJ, Prabpai S, Kongsaeree P..  (2011)  Lanostane and hopane triterpenes from the entomopathogenic fungus Hypocrella sp. BCC 14524.,  74  (10): [PMID:21995505] [10.1021/np200429b]

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

10. Opsenica IM, Verbić TŽ, Tot M, Sciotti RJ, Pybus BS, Djurković-Djaković O, Slavić K, Šolaja BA..  (2015)  Investigation into novel thiophene- and furan-based 4-amino-7-chloroquinolines afforded antimalarials that cure mice.,  23  (9): [PMID:25801154] [10.1016/j.bmc.2015.02.061]

11. Russo CM, Adhikari AA, Wallach DR, Fernandes S, Balch AN, Kerr WG, Chisholm JD..  (2015)  Synthesis and initial evaluation of quinoline-based inhibitors of the SH2-containing inositol 5'-phosphatase (SHIP).,  25  (22): [PMID:26453006] [10.1016/j.bmcl.2015.09.034]

12. British National Formulary (72nd edition), 

13. Stuart Weston, Christopher M. Coleman, Rob Haupt, James Logue, Krystal Matthews and Matthew B. Frieman.  (2020)  Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo,  [10.1101/2020.03.25.008482]

14. Franck Touret, Magali Gilles, Karine Barral, Antoine Nougairède, Etienne Decroly, Xavier de Lamballerie, Bruno Coutard.  (2020)  In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication,  [10.1101/2020.04.03.023846]

15. 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]

16. 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]

17. 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]

Source

Source(6):

• Scientific Literature
• PubChem BioAssays
• 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