torcetrapib

ID: ALA479527

Cas Number: 262352-17-0

PubChem CID: 159325

Product Number: E129832, Order Now?

Max Phase: Phase

Molecular Formula: C26H25F9N2O4

Molecular Weight: 600.48

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Torcetrapib | CP-529,414 | CP-529414 | Torcetrapib|262352-17-0|CP-529414|CP 529414|CP-529,414|(2R,4S)-4-((3,5-Bis-trifluoromethylbenzyl)methoxycarbonylamino)-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester|CHEMBL479527|ethyl (2R,4S)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinoline-1-carboxylate|CHEBI:49203|4N4457MV2U|1(2H)-Quinolinecarboxylic acid, 4-[[[3,5-bis(trifluoromethyl)phenyl]methyl](methShow More⌵

Canonical SMILES:  CCOC(=O)N1c2ccc(C(F)(F)F)cc2[C@@H](N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C(=O)OC)C[C@H]1CC

Standard InChI:  InChI=1S/C26H25F9N2O4/c1-4-18-12-21(19-11-15(24(27,28)29)6-7-20(19)37(18)23(39)41-5-2)36(22(38)40-3)13-14-8-16(25(30,31)32)10-17(9-14)26(33,34)35/h6-11,18,21H,4-5,12-13H2,1-3H3/t18-,21+/m1/s1

Standard InChI Key:  CMSGWTNRGKRWGS-NQIIRXRSSA-N

Molfile:  

     RDKit          2D

 41 43  0  0  1  0  0  0  0  0999 V2000
    0.1292   -0.9542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7417    0.1000    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.1250   -0.2542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7417   -1.3167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7375   -2.0250    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.3542   -0.9625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3542   -0.2542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7417    0.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7792   -0.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0125   -2.3375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7125   -1.3125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1250   -2.3792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4833   -1.3125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7792   -0.9167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3917   -1.9792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1000   -0.9542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4833    0.1083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3917   -1.2667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1667   -1.9792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5542   -2.3375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7792   -2.3375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1667   -1.2750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3542    1.1625    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.1250   -3.0875    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1000   -0.2500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7125   -2.9792    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    3.3917    0.1458    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.4375    0.4125    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.0667   -0.1917    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    4.4167   -2.9125    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    4.6167   -1.9792    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0833   -1.9167    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3625   -1.9292    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3250   -0.9542    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    0.1292    1.1625    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4875   -2.0250    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.9667    0.1000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4875    0.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1000   -2.3792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9667    0.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1000    1.1625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  1  0
  3  1  1  0
  4  1  1  0
  4  5  1  6
  6  4  1  0
  7  6  1  0
  8  2  1  0
  9 14  1  0
 10 15  1  0
 11 16  1  0
 12  5  1  0
 13  1  2  0
 14 22  1  0
 15 21  2  0
 16 13  1  0
 17  3  2  0
 18 14  2  0
 19 20  1  0
 20  5  1  0
 21 19  1  0
 22 19  2  0
 23  8  2  0
 24 12  2  0
 25 16  2  0
 26 10  1  0
 27  9  1  0
 28  9  1  0
 29  9  1  0
 30 10  1  0
 31 10  1  0
 32 11  1  0
 33 11  1  0
 34 11  1  0
 35  8  1  0
 36 12  1  0
  7 37  1  6
 38 35  1  0
 39 36  1  0
 40 37  1  0
 41 38  1  0
 25 17  1  0
  7  2  1  0
 18 15  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA479527

   Torcetrapib

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 600.48

Molecular Weight (Monoisotopic): 600.1671

AlogP: 8.20

#Rotatable Bonds: 5

Polar Surface Area: 59.08

Molecular Species: NEUTRAL

HBA: 4

HBD: ┄

#RO5 Violations: 2

HBA (Lipinski): 6

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): 2

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 7.08

CX LogD: 7.08

Aromatic Rings: 2

Heavy Atoms: 41

QED Weighted: 0.32

Np Likeness Score: -0.85

References

1. Kuo GH, Rano T, Pelton P, Demarest KT, Gibbs AC, Murray WV, Damiano BP, Connelly MA..  (2009)  Design, synthesis, and biological evaluation of (2R,alphaS)-3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)-phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol as potent and orally active cholesteryl ester transfer protein inhibitor.,  52  (6): [PMID:19236017] [10.1021/jm801319d]

2. Schmeck C, Gielen-Haertwig H, Vakalopoulos A, Bischoff H, Li V, Wirtz G, Weber O..  (2010)  Novel tetrahydrochinoline derived CETP inhibitors.,  20  (5): [PMID:20137927] [10.1016/j.bmcl.2010.01.071]

3. Thompson CF, Ali A, Quraishi N, Lu Z, Hammond ML, Sinclair PJ, Anderson MS, Eveland SS, Guo Q, Hyland SA, Milot DP, Sparrow CP, Wright SD..  (2011)  Discovery of substituted biphenyl oxazolidinone inhibitors of cholesteryl ester transfer protein.,  2  (6): [PMID:24900324] [10.1021/ml100309n]

4. Fernandez MC, Escribano A, Mateo AI, Parthasarathy S, Martin de la Nava EM, Wang X, Cockerham SL, Beyer TP, Schmidt RJ, Cao G, Zhang Y, Jones TM, Borel A, Sweetana SA, Cannady EA, Stephenson G, Frank S, Mantlo NB..  (2012)  Design, synthesis and structure-activity-relationship of 1,5-tetrahydronaphthyridines as CETP inhibitors.,  22  (9): [PMID:22497761] [10.1016/j.bmcl.2012.03.075]

5. Escribano A, Mateo AI, Martin de la Nava EM, Mayhugh DR, Cockerham SL, Beyer TP, Schmidt RJ, Cao G, Zhang Y, Jones TM, Borel AG, Sweetana SA, Cannady EA, Mantlo NB..  (2012)  Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors.,  22  (11): [PMID:22543028] [10.1016/j.bmcl.2012.04.042]

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

7. Harikrishnan LS, Finlay HJ, Qiao JX, Kamau MG, Jiang J, Wang TC, Li J, Cooper CB, Poss MA, Adam LP, Taylor DS, Chen AY, Yin X, Sleph PG, Yang RZ, Sitkoff DF, Galella MA, Nirschl DS, Van Kirk K, Miller AV, Huang CS, Chang M, Chen XQ, Salvati ME, Wexler RR, Lawrence RM..  (2012)  Diphenylpyridylethanamine (DPPE) derivatives as cholesteryl ester transfer protein (CETP) inhibitors.,  55  (13): [PMID:22650305] [10.1021/jm300611v]

8. Trieselmann T, Wagner H, Fuchs K, Hamprecht D, Berta D, Cremonesi P, Streicher R, Luippold G, Volz A, Markert M, Nar H..  (2014)  Potent cholesteryl ester transfer protein inhibitors of reduced lipophilicity: 1,1'-spiro-substituted hexahydrofuroquinoline derivatives.,  57  (21): [PMID:25265559] [10.1021/jm500431d]

9. Zhao D, Xie H, Bai C, Liu C, Hao C, Zhao S, Yuan H, Luo C, Wang J, Lin B, Zheng J, Cheng M..  (2016)  Design, synthesis and biological evaluation of N,N-3-phenyl-3-benzylaminopropanamide derivatives as novel cholesteryl ester transfer protein inhibitor.,  24  (8): [PMID:27010500] [10.1016/j.bmc.2015.12.010]

10. Yamada K, Brousseau M, Honma W, Iimura A, Imase H, Iwaki Y, Kawanami T, LaSala D, Liang G, Mitani H, Nonomura K, Ohmori O, Pan M, Rigel DF, Umemura I, Yasoshima K, Zhu G, Mogi M..  (2017)  Discovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma.,  60  (20): [PMID:29035537] [10.1021/acs.jmedchem.7b00900]

11. Chen D, Huang X, Zhou H, Luo H, Wang P, Chang Y, He X, Ni S, Shen Q, Cao G, Sun H, Wen X, Liu J..  (2017)  Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors.,  139  [PMID:28802120] [10.1016/j.ejmech.2017.08.012]

12. Unpublished dataset, 

13. 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]

14. Finlay HJ, Jiang J, Rampulla R, Salvati ME, Qiao JX, Wang TC, Lawrence RM, Harikrishnan LS, Kamau MG, Taylor DS, Chen AYA, Yin X, Huang CS, Chang M, Chen XQ, Sleph PG, Xu C, Li J, Levesque P, Adam LP, Wexler RR..  (2019)  Discovery of a Lead Triphenylethanamine Cholesterol Ester Transfer Protein (CETP) Inhibitor.,  10  (6): [PMID:31223447] [10.1021/acsmedchemlett.9b00086]

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. 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]

18. 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]

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

20. 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]

21. Vachal P, Duffy JL, Campeau LC, Amin RP, Mitra K, Murphy BA, Shao PP, Sinclair PJ, Ye F, Katipally R, Lu Z, Ondeyka D, Chen YH, Zhao K, Sun W, Tyagarajan S, Bao J, Wang SP, Cote J, Lipardi C, Metzger D, Leung D, Hartmann G, Wollenberg GK, Liu J, Tan L, Xu Y, Chen Q, Liu G, Blaustein RO, Johns DG..  (2021)  Invention of MK-8262, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor Backup to Anacetrapib with Best-in-Class Properties.,  64  (18.0): [PMID:34375108] [10.1021/acs.jmedchem.1c00959]

22. Institute for Molecular Medicine Finland - High Throughput Biomedicine Unit.  (2023)  ECBD screening data for assay EOS300108,  [10.6019/EOS300108]

Source

Source(7):

• Scientific Literature
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6
• EU-OPENSCREEN dataset