ID: ALA268439

Max Phase: Preclinical

Molecular Formula: C8H9N5O4S3

Molecular Weight: 335.39

Molecule Type: Small molecule

Representations

Canonical SMILES:  Nc1ccc(S(=O)(=O)Nc2nnc(S(N)(=O)=O)s2)cc1

Standard InChI:  InChI=1S/C8H9N5O4S3/c9-5-1-3-6(4-2-5)20(16,17)13-7-11-12-8(18-7)19(10,14)15/h1-4H,9H2,(H,11,13)(H2,10,14,15)

Standard InChI Key:  BDLSLORLEPSOGW-UHFFFAOYSA-N

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: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 335.39

Molecular Weight (Monoisotopic): 334.9817

AlogP: -0.43

#Rotatable Bonds: 4

Polar Surface Area: 158.13

Molecular Species: ACID

HBA: 8

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 9

HBD (Lipinski): 5

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 6.48

CX Basic pKa: 1.77

CX LogP: -0.62

CX LogD: -1.69

Aromatic Rings: 2

Heavy Atoms: 20

QED Weighted: 0.64

Np Likeness Score: -1.95

References

1. Vullo D, Franchi M, Gallori E, Pastorek J, Scozzafava A, Pastorekova S, Supuran CT..  (2003)  Carbonic anhydrase inhibitors: inhibition of the tumor-associated isozyme IX with aromatic and heterocyclic sulfonamides.,  13  (6): [PMID:12643899] [10.1016/s0960-894x(03)00091-x]

2. Scozzafava A, Supuran CT..  (2000)  Carbonic anhydrase inhibitors: synthesis of N-morpholylthiocarbonylsulfenylamino aromatic/heterocyclic sulfonamides and their interaction with isozymes I, II and IV.,  10  (10): [PMID:10843231] [10.1016/s0960-894x(00)00178-5]

3. Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT..  (2004)  Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides.,  47  (5): [PMID:14971907] [10.1021/jm031057+]

4. Ilies MA, Vullo D, Pastorek J, Scozzafava A, Ilies M, Caproiu MT, Pastorekova S, Supuran CT..  (2003)  Carbonic anhydrase inhibitors. Inhibition of tumor-associated isozyme IX by halogenosulfanilamide and halogenophenylaminobenzolamide derivatives.,  46  (11): [PMID:12747790] [10.1021/jm021123s]

5. Casey JR, Morgan PE, Vullo D, Scozzafava A, Mastrolorenzo A, Supuran CT..  (2004)  Carbonic anhydrase inhibitors. Design of selective, membrane-impermeant inhibitors targeting the human tumor-associated isozyme IX.,  47  (9): [PMID:15084132] [10.1021/jm031079w]

6. Scozzafava A, Briganti F, Ilies MA, Supuran CT..  (2000)  Carbonic anhydrase inhibitors: synthesis of membrane-impermeant low molecular weight sulfonamides possessing in vivo selectivity for the membrane-bound versus cytosolic isozymes.,  43  (2): [PMID:10649985] [10.1021/jm990479+]

7. Jaiswal M, Khadikar PV, Scozzafava A, Supuran CT..  (2004)  Carbonic anhydrase inhibitors: the first QSAR study on inhibition of tumor-associated isoenzyme IX with aromatic and heterocyclic sulfonamides.,  14  (12): [PMID:15149691] [10.1016/j.bmcl.2004.03.099]

8. Scozzafava A, Briganti F, Mincione G, Menabuoni L, Mincione F, Supuran CT..  (1999)  Carbonic anhydrase inhibitors: synthesis of water-soluble, aminoacyl/dipeptidyl sulfonamides possessing long-lasting intraocular pressure-lowering properties via the topical route.,  42  (18): [PMID:10479300] [10.1021/jm9901879]

9. Lehtonen JM, Parkkila S, Vullo D, Casini A, Scozzafava A, Supuran CT..  (2004)  Carbonic anhydrase inhibitors. Inhibition of cytosolic isozyme XIII with aromatic and heterocyclic sulfonamides: a novel target for the drug design.,  14  (14): [PMID:15203157] [10.1016/j.bmcl.2004.04.106]

10. Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT..  (2005)  Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides.,  15  (17): [PMID:16039848] [10.1016/j.bmcl.2005.06.055]

11. Vullo D, Innocenti A, Nishimori I, Pastorek J, Scozzafava A, Pastoreková S, Supuran CT..  (2005)  Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma drugs?,  15  (4): [PMID:15686894] [10.1016/j.bmcl.2004.12.053]

12. Cecchi A, Winum JY, Innocenti A, Vullo D, Montero JL, Scozzafava A, Supuran CT..  (2004)  Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides derived from 4-isothiocyanato-benzolamide.,  14  (23): [PMID:15501039] [10.1016/j.bmcl.2004.09.062]

13. Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT..  (2005)  Carbonic anhydrase inhibitors. The mitochondrial isozyme VB as a new target for sulfonamide and sulfamate inhibitors.,  48  (24): [PMID:16302824] [10.1021/jm050483n]

14. Nishimori I, Minakuchi T, Morimoto K, Sano S, Onishi S, Takeuchi H, Vullo D, Scozzafava A, Supuran CT..  (2006)  Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs.,  49  (6): [PMID:16539401] [10.1021/jm0512600]

15. Nishimori I, Vullo D, Minakuchi T, Morimoto K, Onishi S, Scozzafava A, Supuran CT..  (2006)  Carbonic anhydrase inhibitors: cloning and sulfonamide inhibition studies of a carboxyterminal truncated alpha-carbonic anhydrase from Helicobacter pylori.,  16  (8): [PMID:16459077] [10.1016/j.bmcl.2006.01.044]

16. Nishimori I, Minakuchi T, Onishi S, Vullo D, Scozzafava A, Supuran CT..  (2007)  Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition studies of the human secretory isoform VI, a new target for sulfonamide and sulfamate inhibitors.,  50  (2): [PMID:17228881] [10.1021/jm0612057]

17. Nishimori I, Minakuchi T, Kohsaki T, Onishi S, Takeuchi H, Vullo D, Scozzafava A, Supuran CT..  (2007)  Carbonic anhydrase inhibitors: the beta-carbonic anhydrase from Helicobacter pylori is a new target for sulfonamide and sulfamate inhibitors.,  17  (13): [PMID:17482815] [10.1016/j.bmcl.2007.04.063]

18. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT..  (2007)  Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides.,  15  (23): [PMID:17826101] [10.1016/j.bmc.2007.08.037]

19. Isik S, Kockar F, Aydin M, Arslan O, Guler OO, Innocenti A, Scozzafava A, Supuran CT..  (2009)  Carbonic anhydrase inhibitors: inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates.,  17  (3): [PMID:19124253] [10.1016/j.bmc.2008.12.035]

20. Minakuchi T, Nishimori I, Vullo D, Scozzafava A, Supuran CT..  (2009)  Molecular cloning, characterization, and inhibition studies of the Rv1284 beta-carbonic anhydrase from Mycobacterium tuberculosis with sulfonamides and a sulfamate.,  52  (8): [PMID:19317447] [10.1021/jm9000488]

21. Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Innocenti A, Supuran CT..  (2009)  Carbonic anhydrase inhibitors. Cloning, characterization, and inhibition studies of a new beta-carbonic anhydrase from Mycobacterium tuberculosis.,  52  (9): [PMID:19338333] [10.1021/jm9003126]

22. Innocenti A, Hall RA, Schlicker C, Scozzafava A, Steegborn C, Mühlschlegel FA, Supuran CT..  (2009)  Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides.,  17  (13): [PMID:19450983] [10.1016/j.bmc.2009.05.002]

23. Bertucci A, Innocenti A, Zoccola D, Scozzafava A, Tambutté S, Supuran CT..  (2009)  Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides.,  17  (14): [PMID:19520577] [10.1016/j.bmc.2009.05.063]

24. Carta F, Maresca A, Covarrubias AS, Mowbray SL, Jones TA, Supuran CT..  (2009)  Carbonic anhydrase inhibitors. Characterization and inhibition studies of the most active beta-carbonic anhydrase from Mycobacterium tuberculosis, Rv3588c.,  19  (23): [PMID:19846301] [10.1016/j.bmcl.2009.10.009]

25. Joseph P, Turtaut F, Ouahrani-Bettache S, Montero JL, Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Köhler S, Winum JY, Supuran CT..  (2010)  Cloning, characterization, and inhibition studies of a beta-carbonic anhydrase from Brucella suis.,  53  (5): [PMID:20158185] [10.1021/jm901855h]

26. Oltulu O, Yaşar MM, Eroğlu E..  (2009)  A QSAR study on relationship between structure of sulfonamides and their carbonic anhydrase inhibitory activity using the eigenvalue (EVA) method.,  44  (9): [PMID:19303173] [10.1016/j.ejmech.2009.02.016]

27. Bertucci A, Innocenti A, Scozzafava A, Tambutté S, Zoccola D, Supuran CT..  (2011)  Carbonic anhydrase inhibitors. Inhibition studies with anions and sulfonamides of a new cytosolic enzyme from the scleractinian coral Stylophora pistillata.,  21  (2): [PMID:21208801] [10.1016/j.bmcl.2010.11.124]

28. Joseph P, Ouahrani-Bettache S, Montero JL, Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Winum JY, Köhler S, Supuran CT..  (2011)  A new β-carbonic anhydrase from Brucella suis, its cloning, characterization, and inhibition with sulfonamides and sulfamates, leading to impaired pathogen growth.,  19  (3): [PMID:21251841] [10.1016/j.bmc.2010.12.048]

29. Ahad AM, Zuohe S, Du-Cuny L, Moses SA, Zhou LL, Zhang S, Powis G, Meuillet EJ, Mash EA..  (2011)  Development of sulfonamide AKT PH domain inhibitors.,  19  (6): [PMID:21353784] [10.1016/j.bmc.2011.01.049]

30. Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Supuran CT..  (2011)  Inhibition studies of the β-carbonic anhydrases from the bacterial pathogen Salmonella enterica serovar Typhimurium with sulfonamides and sulfamates.,  19  (16): [PMID:21757360] [10.1016/j.bmc.2011.06.038]

31. Ohradanova A, Vullo D, Pastorekova S, Pastorek J, Jackson DJ, Wörheide G, Supuran CT..  (2012)  Cloning, characterization and sulfonamide inhibition studies of an α-carbonic anhydrase from the living fossil sponge Astrosclera willeyana.,  20  (4): [PMID:22285172] [10.1016/j.bmc.2012.01.007]

32. PubChem BioAssay data set, 

33. Hewitson KS, Vullo D, Scozzafava A, Mastrolorenzo A, Supuran CT..  (2012)  Molecular cloning, characterization, and inhibition studies of a β-carbonic anhydrase from Malassezia globosa, a potential antidandruff target.,  55  (7): [PMID:22424239] [10.1021/jm300203r]

34. Del Prete S, Isik S, Vullo D, De Luca V, Carginale V, Scozzafava A, Supuran CT, Capasso C..  (2012)  DNA cloning, characterization, and inhibition studies of an α-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae.,  55  (23): [PMID:23181552] [10.1021/jm301611m]

35. Pan P, Vermelho AB, Capaci Rodrigues G, Scozzafava A, Tolvanen ME, Parkkila S, Capasso C, Supuran CT..  (2013)  Cloning, characterization, and sulfonamide and thiol inhibition studies of an α-carbonic anhydrase from Trypanosoma cruzi, the causative agent of Chagas disease.,  56  (4): [PMID:23391336] [10.1021/jm4000616]

36. Vullo D, Luca VD, Scozzafava A, Carginale V, Rossi M, Supuran CT, Capasso C..  (2013)  The alpha-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 is highly susceptible to inhibition by sulfonamides.,  21  (6): [PMID:22883029] [10.1016/j.bmc.2012.07.024]

37. Vullo D, Leewattanapasuk W, Mühlschlegel FA, Mastrolorenzo A, Capasso C, Supuran CT..  (2013)  Carbonic anhydrase inhibitors: inhibition of the β-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides, sulfamates and sulfamides.,  23  (9): [PMID:23511020] [10.1016/j.bmcl.2013.02.092]

38. Syrjänen L, Vermelho AB, Rodrigues Ide A, Corte-Real S, Salonen T, Pan P, Vullo D, Parkkila S, Capasso C, Supuran CT..  (2013)  Cloning, characterization, and inhibition studies of a β-carbonic anhydrase from Leishmania donovani chagasi, the protozoan parasite responsible for leishmaniasis.,  56  (18): [PMID:23977960] [10.1021/jm400939k]

39. Vullo D, Del Prete S, Osman SM, De Luca V, Scozzafava A, Alothman Z, Supuran CT, Capasso C..  (2014)  Sulfonamide inhibition studies of the δ-carbonic anhydrase from the diatom Thalassiosira weissflogii.,  24  (1): [PMID:24314394] [10.1016/j.bmcl.2013.11.021]

40. Vullo D, Del Prete S, Osman SM, De Luca V, Scozzafava A, Alothman Z, Supuran CT, Capasso C..  (2014)  Sulfonamide inhibition studies of the γ-carbonic anhydrase from the oral pathogen Porphyromonas gingivalis.,  24  (1): [PMID:24316122] [10.1016/j.bmcl.2013.11.030]

41. Nishimori I, Vullo D, Minakuchi T, Scozzafava A, Capasso C, Supuran CT..  (2014)  Sulfonamide inhibition studies of two β-carbonic anhydrases from the bacterial pathogen Legionella pneumophila.,  22  (11): [PMID:24792813] [10.1016/j.bmc.2014.04.006]

42. Prete SD, Vullo D, Osman SM, Scozzafava A, AlOthman Z, Capasso C, Supuran CT..  (2014)  Sulfonamide inhibition study of the carbonic anhydrases from the bacterial pathogen Porphyromonas gingivalis: the β-class (PgiCAb) versus the γ-class (PgiCA) enzymes.,  22  (17): [PMID:25129169] [10.1016/j.bmc.2014.07.048]

43. Vullo D, Del Prete S, Fisher GM, Andrews KT, Poulsen SA, Capasso C, Supuran CT..  (2015)  Sulfonamide inhibition studies of the η-class carbonic anhydrase from the malaria pathogen Plasmodium falciparum.,  23  (3): [PMID:25533402] [10.1016/j.bmc.2014.12.009]

44. Syrjänen L, Kuuslahti M, Tolvanen M, Vullo D, Parkkila S, Supuran CT..  (2015)  The β-carbonic anhydrase from the malaria mosquito Anopheles gambiae is highly inhibited by sulfonamides.,  23  (10): [PMID:25882523] [10.1016/j.bmc.2015.03.081]

45. Vullo D, De Luca V, Del Prete S, Carginale V, Scozzafava A, Capasso C, Supuran CT..  (2015)  Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic cyanobacterium Nostoc commune.,  23  (8): [PMID:25773015] [10.1016/j.bmc.2015.02.045]

46. Dedeoglu N, DeLuca V, Isik S, Yildirim H, Kockar F, Capasso C, Supuran CT..  (2015)  Sulfonamide inhibition study of the β-class carbonic anhydrase from the caries producing pathogen Streptococcus mutans.,  25  (11): [PMID:25913199] [10.1016/j.bmcl.2015.04.037]

47. Vullo D, De Luca V, Del Prete S, Carginale V, Scozzafava A, Capasso C, Supuran CT..  (2015)  Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic bacterium Pseudoalteromonas haloplanktis.,  25  (17): [PMID:26174556] [10.1016/j.bmcl.2015.06.079]

48. Vullo D, Bhatt A, Mahon BP, McKenna R, Supuran CT..  (2016)  Sulfonamide inhibition studies of the α-carbonic anhydrase from the gammaproteobacterium Thiomicrospira crunogena XCL-2, TcruCA.,  26  (2): [PMID:26691758] [10.1016/j.bmcl.2015.11.104]

49. Del Prete S, Vullo D, De Luca V, Carginale V, Ferraroni M, Osman SM, AlOthman Z, Supuran CT, Capasso C..  (2016)  Sulfonamide inhibition studies of the β-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae.,  24  (5): [PMID:26850377] [10.1016/j.bmc.2016.01.037]

50. Vullo D, De Luca V, Del Prete S, Carginale V, Scozzafava A, Osman SM, AlOthman Z, Capasso C, Supuran CT..  (2016)  Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic bacterium Colwellia psychrerythraea.,  26  (4): [PMID:26832216] [10.1016/j.bmcl.2016.01.023]

51. Eminoğlu A, Vullo D, Aşık A, Çolak DN, Çanakçı S, Beldüz AO, Supuran CT..  (2016)  Sulfonamide inhibition studies of the β-carbonic anhydrase from the newly discovered bacterium Enterobacter sp. B13.,  26  (7): [PMID:26920803] [10.1016/j.bmcl.2016.02.032]

52. Del Prete S, Vullo D, De Luca V, Carginale V, Osman SM, AlOthman Z, Supuran CT, Capasso C..  (2016)  Comparison of the sulfonamide inhibition profiles of the α-, β- and γ-carbonic anhydrases from the pathogenic bacterium Vibrio cholerae.,  26  (8): [PMID:26972117] [10.1016/j.bmcl.2016.03.014]

53. Del Prete S, Vullo D, Di Fonzo P, Osman SM, AlOthman Z, Donald WA, Supuran CT, Capasso C..  (2017)  Sulfonamide inhibition profile of the γ-carbonic anhydrase identified in the genome of the pathogenic bacterium Burkholderia pseudomallei the etiological agent responsible of melioidosis.,  27  (3): [PMID:28025002] [10.1016/j.bmcl.2016.12.035]

54. Del Prete S, Vullo D, Osman SM, AlOthman Z, Supuran CT, Capasso C..  (2017)  Sulfonamide inhibition profiles of the β-carbonic anhydrase from the pathogenic bacterium Francisella tularensis responsible of the febrile illness tularemia.,  25  (13): [PMID:28511911] [10.1016/j.bmc.2017.05.007]

55. Del Prete S, Vullo D, De Luca V, Carginale V, Osman SM, AlOthman Z, Supuran CT, Capasso C..  (2016)  Cloning, expression, purification and sulfonamide inhibition profile of the complete domain of the η-carbonic anhydrase from Plasmodium falciparum.,  26  (17): [PMID:27485387] [10.1016/j.bmcl.2016.07.060]

56. Mancuso F,De Luca L,Angeli A,Berrino E,Del Prete S,Capasso C,Supuran CT,Gitto R.  (2020)  In Silico-Guided Identification of New Potent Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae.,  11  (11): [PMID:33214843] [10.1021/acsmedchemlett.0c00417]

Source

Source(2):

• Scientific Literature
• PubChem BioAssays