Dabigatran etexilate

ID: ALA539697

PubChem CID: 9578572

Max Phase: Approved

First Approval: 2008

Molecular Formula: C34H41N7O5

Molecular Weight: 627.75

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Dabigatran etexilate | BIBR 1048 | BIBR 1048 BS RS1 | BIBR-1048 | BIBR-1048-BS-RS1 | CHEBI:70746|Pradaxa (TN)|Dabigatran etexilate methanesulfonate|SCHEMBL505829|CHEMBL539697|Dabigatran etexilate (USAN/INN)|BDBM50432209|s2154|D07144|AB01274780-01|AB01274780_02|A815191|3-[[[2-[[4-[(E)-amino-[hexoxy(oxo)methyl]iminomethyl]anilino]methyl]-1-methyl-5-benzimidazolyl]-oxomethyl]-(2-pyridinyl)amino]propanoic acid ethyl ester|ethyl 3-[[2-[[[4-[(E)-N'-hexoxycarbonylcarbamimidoyl]phenyl]amino]methyl]-1-meShow More⌵

Synonyms from Alternative Forms(5): Dabigatran etexilate mesilate | Dabigatran etexilate mesylate | BIBR 1048 MS | BIBR-1048-MS | Pradaxa

Trade Names(1): Pradaxa

Canonical SMILES:  CCCCCCOC(=O)NC(=N)c1ccc(NCc2nc3cc(C(=O)N(CCC(=O)OCC)c4ccccn4)ccc3n2C)cc1

Standard InChI:  InChI=1S/C34H41N7O5/c1-4-6-7-10-21-46-34(44)39-32(35)24-12-15-26(16-13-24)37-23-30-38-27-22-25(14-17-28(27)40(30)3)33(43)41(20-18-31(42)45-5-2)29-11-8-9-19-36-29/h8-9,11-17,19,22,37H,4-7,10,18,20-21,23H2,1-3H3,(H2,35,39,44)

Standard InChI Key:  KSGXQBZTULBEEQ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 46 49  0  0  0  0  0  0  0  0999 V2000
   -1.2500    0.2708    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7333   -0.3958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2500   -1.0625    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.3917    0.0167    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4667    0.0167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6792    0.4292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4667   -0.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.6792    1.0333    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2667    0.3208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9625    0.0167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2667    1.7458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3917   -0.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2500    0.4292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1083    0.4292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8208    0.0167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2500   -1.2208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5375    0.4292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4458    0.3208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.6792   -0.3958    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5583   -0.3958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6792   -1.2208    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.6792    1.2542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.9625   -0.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.6792    2.4625    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9708    0.3208    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.5375    1.2542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.0333    1.0333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.0333   -0.3958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7958    0.3208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4458    1.7458    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5042   -1.8458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2083   -0.3958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2083    1.0333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2500    0.0167    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.1083   -1.2208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6792   -2.0458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.0333    2.4625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9667    0.4292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2083    2.4625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5583    2.4625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9708    1.7458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7958    1.7458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6792    0.0167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1083   -2.0458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3917   -2.4583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7333    2.4625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  2  1  0
  4  6  1  0
  5  1  1  0
  6 10  1  0
  7  5  2  0
  8  9  1  0
  9 18  1  0
 10 13  2  0
 11  8  1  0
 12  4  1  0
 13  5  1  0
 14  4  1  0
 15 14  1  0
 16  7  1  0
 17 15  1  0
 18 27  1  0
 19  9  2  0
 20  2  1  0
 21 12  2  0
 22  6  2  0
 23 10  1  0
 24 11  2  0
 25 20  1  0
 26 17  2  0
 27 33  2  0
 28 32  1  0
 29 25  1  0
 30 11  1  0
 31  3  1  0
 32 29  2  0
 33 29  1  0
 34 17  1  0
 35 12  1  0
 36 21  1  0
 37 30  1  0
 38 34  1  0
 39 37  1  0
 40 41  1  0
 41 42  1  0
 42 39  1  0
 43 38  1  0
 44 35  2  0
 45 44  1  0
 46 40  1  0
  7  3  1  0
 23 16  2  0
 28 18  2  0
 45 36  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA539697

   DABIGATRAN ETEXILATE

2. Alternative Forms:

   

   ALA539697

   Dabigatran etexilate methanesulfonate

Molecule Features

Natural Product: Yes

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: Yes

Chirality: Yes

Availability: Yes

Prodrug: Yes

Calculated Properties

Molecular Weight: 627.75

Molecular Weight (Monoisotopic): 627.3169

AlogP: 5.81

#Rotatable Bonds: 15

Polar Surface Area: 151.53

Molecular Species: NEUTRAL

HBA: 10

HBD: 3

#RO5 Violations: 2

HBA (Lipinski): 12

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 10.17

CX Basic pKa: 3.82

CX LogP: 4.99

CX LogD: 4.99

Aromatic Rings: 4

Heavy Atoms: 46

QED Weighted: 0.06

Np Likeness Score: -1.35

References

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

4. Yang XZ, Diao XJ, Yang WH, Li F, He GW, Gong GQ, Xu YG..  (2013)  Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate.,  23  (7): [PMID:23466230] [10.1016/j.bmcl.2013.01.126]

5. Park HD, Lee SH, Kim TH, Lee SH, Cho KH, Kim A..  (2013)  Antithrombotic effects of LB30870, a potent, orally active, selective and direct thrombin inhibitor, and pharmacokinetics of its prodrug.,  23  (17): [PMID:23899618] [10.1016/j.bmcl.2013.07.008]

6. Meneyrol J, Follmann M, Lassalle G, Wehner V, Barre G, Rousseaux T, Altenburger JM, Petit F, Bocskei Z, Schreuder H, Alet N, Herault JP, Millet L, Dol F, Florian P, Schaeffer P, Sadoun F, Klieber S, Briot C, Bono F, Herbert JM..  (2013)  5-Chlorothiophene-2-carboxylic acid [(S)-2-[2-methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a selective and potent orally active dual thrombin and factor Xa inhibitor.,  56  (23): [PMID:24175584] [10.1021/jm4005835]

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9. Chen D, Wang S, Diao X, Zhu Q, Shen H, Han X, Wang Y, Gong G, Xu Y..  (2015)  Design, synthesis and antithrombotic evaluation of novel dabigatran etexilate analogs, a new series of non-peptides thrombin inhibitors.,  23  (23): [PMID:26537784] [10.1016/j.bmc.2015.10.036]

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14. Ren W, Ren Y, Wang S..  (2016)  Design, synthesis, anticoagulant activity evaluation and molecular docking studies of a class of N-ethyl dabigatran derivatives.,  120  [PMID:27187866] [10.1016/j.ejmech.2016.05.020]

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18. Unpublished dataset, 

19. 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]

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22. 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]

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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. 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]

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28. 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]

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Source

Source(10):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names
• WHO Anatomical Therapeutic Chemical Classification
• British National Formulary
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6
• Zimmerman Lab Biotransformation data Dec 2023