N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-isopropylbenzenesulfonamide

ID: ALA3235901

Chembl Id: CHEMBL3235901

PubChem CID: 2133805

Max Phase: Preclinical

Molecular Formula: C21H20N4O3S2

Molecular Weight: 440.55

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(C)c1ccc(S(=O)(=O)Nc2cc(Sc3nc[nH]n3)c(O)c3ccccc23)cc1

Standard InChI:  InChI=1S/C21H20N4O3S2/c1-13(2)14-7-9-15(10-8-14)30(27,28)25-18-11-19(29-21-22-12-23-24-21)20(26)17-6-4-3-5-16(17)18/h3-13,25-26H,1-2H3,(H,22,23,24)

Standard InChI Key:  MFEOAVQPFYZKIH-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA3235901

   N-[4-hydroxy-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-yl]-4-propan-2-ylbenzenesulfonamide

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

Calculated Properties

Molecular Weight: 440.55

Molecular Weight (Monoisotopic): 440.0977

AlogP: 4.74

#Rotatable Bonds: 6

Polar Surface Area: 107.97

Molecular Species: ACID

HBA: 6

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 6.23

CX Basic pKa: 0.61

CX LogP: 4.88

CX LogD: 3.43

Aromatic Rings: 4

Heavy Atoms: 30

QED Weighted: 0.37

Np Likeness Score: -1.28

References

1. Zhuang C, Narayanapillai S, Zhang W, Sham YY, Xing C..  (2014)  Rapid identification of Keap1-Nrf2 small-molecule inhibitors through structure-based virtual screening and hit-based substructure search.,  57  (3): [PMID:24417449] [10.1021/jm4017174]

2. Dahlin JL, Nissink JW, Strasser JM, Francis S, Higgins L, Zhou H, Zhang Z, Walters MA..  (2015)  PAINS in the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS.,  58  (5): [PMID:25634295] [10.1021/jm5019093]

3. Bertrand HC, Schaap M, Baird L, Georgakopoulos ND, Fowkes A, Thiollier C, Kachi H, Dinkova-Kostova AT, Wells G..  (2015)  Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1-Nrf2 Protein-Protein Interaction.,  58  (18): [PMID:26348784] [10.1021/acs.jmedchem.5b00602]

4. Tran KT, Pallesen JS, Solbak SMØ, Narayanan D, Baig A, Zang J, Aguayo-Orozco A, Carmona RMC, Garcia AD, Bach A..  (2019)  A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity.,  62  (17): [PMID:31411465] [10.1021/acs.jmedchem.9b00723]

5. Lee S, Abed DA, Nguyen MU, Verzi MP, Hu L..  (2022)  Structure-activity relationships of 1,4-bis(arylsulfonamido)-benzene or naphthalene-N,N'-diacetic acids with varying C2-substituents as inhibitors of Keap1-Nrf2 protein-protein interaction.,  237  [PMID:35462166] [10.1016/j.ejmech.2022.114380]

6. Georgakopoulos N, Talapatra S, Dikovskaya D, Dayalan Naidu S, Higgins M, Gatliff J, Ayhan A, Nikoloudaki R, Schaap M, Valko K, Javid F, Dinkova-Kostova AT, Kozielski F, Wells G..  (2022)  Phenyl Bis-Sulfonamide Keap1-Nrf2 Protein-Protein Interaction Inhibitors with an Alternative Binding Mode.,  65  (10.0): [PMID:35549469] [10.1021/acs.jmedchem.2c00457]

7. Mou Y, Wen S, Li YX, Gao XX, Zhang X, Jiang ZY..  (2020)  Recent progress in Keap1-Nrf2 protein-protein interaction inhibitors.,  202  [PMID:32668381] [10.1016/j.ejmech.2020.112532]

Source

Source(1):

• Scientific Literature