N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-sulfamide

ID: ALA2165326

Cas Number: 1103522-45-7

PubChem CID: 25099191

Product Number: A607692, Order Now?

Max Phase: Phase

Molecular Formula: C16H14Br2N6O4S

Molecular Weight: 546.20

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Act-132577 | Aprocitentan | Macitentan metabolite m6 | ACT-132577 | Aprocitentan|1103522-45-7|ACT-132577|N-Despropyl-macitentan|Aprocitentan [USAN]|Macitentan metabolite m6|MZI81HV01P|Aprocitentan (ACT-132577)|CHEMBL2165326|CHEBI:76609|5-(4-bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-(sulfamoylamino)pyrimidine|N-[5-(4-bromophenyl)-6-{2-[(5-bromopyrimidin-2-yl)oxy]ethoxy}pyrimidin-4-yl]sulfuric diamide|N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]SulfamideShow More⌵

Canonical SMILES:  NS(=O)(=O)Nc1ncnc(OCCOc2ncc(Br)cn2)c1-c1ccc(Br)cc1

Standard InChI:  InChI=1S/C16H14Br2N6O4S/c17-11-3-1-10(2-4-11)13-14(24-29(19,25)26)22-9-23-15(13)27-5-6-28-16-20-7-12(18)8-21-16/h1-4,7-9H,5-6H2,(H2,19,25,26)(H,22,23,24)

Standard InChI Key:  DKULOVKANLVDEA-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 29 31  0  0  0  0  0  0  0  0999 V2000
   -4.3085    2.2612    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   -5.0230    1.8487    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3085    0.6112    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5940    1.0237    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5940    1.8487    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8796    0.6112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1651    1.0237    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1651    1.8487    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4506    2.2612    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4506    0.6112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7362    1.0237    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7362    1.8487    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3085   -0.2139    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5940   -0.6264    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8796   -0.2139    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1651   -0.6264    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4506   -0.2139    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7362   -0.6264    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0217   -0.2139    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.6927   -0.6264    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4072   -0.2139    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.6927   -1.4514    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.4072   -1.8639    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1217   -1.4514    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1217   -0.6264    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7934    2.9286    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8592    2.9531    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0443    2.2980    0.0000 Br  0  0  0  0  0  0  0  0  0  0  0  0
    2.8362   -1.8639    0.0000 Br  0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  3  4  2  0
  4  5  1  0
  1  5  1  0
  6  7  1  0
  7  8  2  0
  4  6  1  0
 10 11  2  0
 11 12  1  0
  9 12  2  0
  7 10  1  0
  9  8  1  0
 13 14  2  0
 14 15  1  0
  3 13  1  0
 15  6  2  0
 16 17  1  0
 15 16  1  0
 18 19  1  0
 17 18  1  0
 20 21  1  0
 19 20  1  0
 22 23  1  0
 23 24  2  0
 24 25  1  0
 20 22  2  0
 21 25  2  0
  1 26  2  0
  1 27  2  0
 12 28  1  0
 24 29  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA2165326

   aprocitentan

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: 546.20

Molecular Weight (Monoisotopic): 543.9164

AlogP: 2.53

#Rotatable Bonds: 8

Polar Surface Area: 142.21

Molecular Species: NEUTRAL

HBA: 8

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 7.79

CX Basic pKa: 3.26

CX LogP: 2.58

CX LogD: 2.45

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.41

Np Likeness Score: -1.19

References

1. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T..  (2012)  The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist.,  55  (17): [PMID:22862294] [10.1021/jm3009103]

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

3. Unpublished dataset, 

4. 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]

5. Boss C, Bolli MH, Gatfield J..  (2016)  From bosentan (Tracleer®) to macitentan (Opsumit®): The medicinal chemistry perspective.,  26  (15): [PMID:27321813] [10.1016/j.bmcl.2016.06.014]

6. 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]

7. 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]

8. 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]

Source

Source(5):

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