ID: ALA2402207

Max Phase: Preclinical

Molecular Formula: C24H22N2O6S2

Molecular Weight: 498.58

Molecule Type: Small molecule

Representations

Canonical SMILES:  COc1ccc(S(=O)(=O)Nc2ccc(NS(=O)(=O)c3ccc(OC)cc3)c3ccccc23)cc1

Standard InChI:  InChI=1S/C24H22N2O6S2/c1-31-17-7-11-19(12-8-17)33(27,28)25-23-15-16-24(22-6-4-3-5-21(22)23)26-34(29,30)20-13-9-18(32-2)10-14-20/h3-16,25-26H,1-2H3

Standard InChI Key:  XLLVCULLOGKYOO-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: 498.58

Molecular Weight (Monoisotopic): 498.0919

AlogP: 4.46

#Rotatable Bonds: 8

Polar Surface Area: 110.80

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 7.77

CX Basic pKa:

CX LogP: 3.62

CX LogD: 3.47

Aromatic Rings: 4

Heavy Atoms: 34

QED Weighted: 0.37

Np Likeness Score: -0.77

References

1. Marcotte D, Zeng W, Hus JC, McKenzie A, Hession C, Jin P, Bergeron C, Lugovskoy A, Enyedy I, Cuervo H, Wang D, Atmanene C, Roecklin D, Vecchi M, Vivat V, Kraemer J, Winkler D, Hong V, Chao J, Lukashev M, Silvian L..  (2013)  Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.,  21  (14): [PMID:23647822] [10.1016/j.bmc.2013.04.019]

2. 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]

3. Jiang ZY, Lu MC, Xu LL, Yang TT, Xi MY, Xu XL, Guo XK, Zhang XJ, You QD, Sun HP..  (2014)  Discovery of potent Keap1-Nrf2 protein-protein interaction inhibitor based on molecular binding determinants analysis.,  57  (6): [PMID:24512214] [10.1021/jm5000529]

4. 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]

5. Jain AD, Potteti H, Richardson BG, Kingsley L, Luciano JP, Ryuzoji AF, Lee H, Krunic A, Mesecar AD, Reddy SP, Moore TW..  (2015)  Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators.,  103  [PMID:26363505] [10.1016/j.ejmech.2015.08.049]

6. Nasiri HR, Linge S, Ullmann D..  (2016)  Thermodynamic profiling of inhibitors of Nrf2:Keap1 interactions.,  26  (2): [PMID:26653613] [10.1016/j.bmcl.2015.11.082]

7. Yasuda D, Nakajima M, Yuasa A, Obata R, Takahashi K, Ohe T, Ichimura Y, Komatsu M, Yamamoto M, Imamura R, Kojima H, Okabe T, Nagano T, Mashino T..  (2016)  Synthesis of Keap1-phosphorylated p62 and Keap1-Nrf2 protein-protein interaction inhibitors and their inhibitory activity.,  26  (24): [PMID:27839920] [10.1016/j.bmcl.2016.10.083]

8. Yasuda D, Yuasa A, Obata R, Nakajima M, Takahashi K, Ohe T, Ichimura Y, Komatsu M, Yamamoto M, Imamura R, Kojima H, Okabe T, Nagano T, Mashino T..  (2017)  Discovery of benzo[g]indoles as a novel class of non-covalent Keap1-Nrf2 protein-protein interaction inhibitor.,  27  (22): [PMID:29037947] [10.1016/j.bmcl.2017.10.008]

9. Richardson BG, Jain AD, Potteti HR, Lazzara PR, David BP, Tamatam CR, Choma E, Skowron K, Dye K, Siddiqui Z, Wang YT, Krunic A, Reddy SP, Moore TW..  (2018)  Replacement of a Naphthalene Scaffold in Kelch-like ECH-Associated Protein 1 (KEAP1)/Nuclear Factor (Erythroid-derived 2)-like 2 (NRF2) Inhibitors.,  61  (17): [PMID:30122040] [10.1021/acs.jmedchem.8b01133]

10. 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]

11. Ma B, Lucas B, Capacci A, Lin EY, Jones JH, Dechantsreiter M, Enyedy I, Marcotte D, Xiao G, Li B, Richter K..  (2020)  Design, synthesis and identification of novel, orally bioavailable non-covalent Nrf2 activators.,  30  (4): [PMID:31898999] [10.1016/j.bmcl.2019.126852]

12. 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]

Source

Source(1):

• Scientific Literature