ID: ALA2396674

Max Phase: Preclinical

Molecular Formula: C28H32Cl2FN3O3

Molecular Weight: 548.49

Molecule Type: Small molecule

Representations

Canonical SMILES:  CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2F)[C@]12C(=O)Nc1cc(Cl)ccc12

Standard InChI:  InChI=1S/C28H32Cl2FN3O3/c1-26(2,3)13-20-28(17-9-8-14(29)10-19(17)33-25(28)36)21(16-6-5-7-18(30)22(16)31)23(34-20)24(35)32-15-11-27(4,37)12-15/h5-10,15,20-21,23,34,37H,11-13H2,1-4H3,(H,32,35)(H,33,36)/t15-,20-,21-,23+,27+,28+/m0/s1

Standard InChI Key:  MZBOZBMARIQZGX-GRRGFIRHSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: Yes

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 548.49

Molecular Weight (Monoisotopic): 547.1805

AlogP: 4.91

#Rotatable Bonds: 4

Polar Surface Area: 90.46

Molecular Species: BASE

HBA: 4

HBD: 4

#RO5 Violations: 1

HBA (Lipinski): 6

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 12.88

CX Basic pKa: 8.99

CX LogP: 4.33

CX LogD: 2.74

Aromatic Rings: 2

Heavy Atoms: 37

QED Weighted: 0.44

Np Likeness Score: -0.15

References

1. Zhao Y, Yu S, Sun W, Liu L, Lu J, McEachern D, Shargary S, Bernard D, Li X, Zhao T, Zou P, Sun D, Wang S..  (2013)  A potent small-molecule inhibitor of the MDM2-p53 interaction (MI-888) achieved complete and durable tumor regression in mice.,  56  (13): [PMID:23786219] [10.1021/jm4005708]

2. Blackburn TJ, Ahmed S, Coxon CR, Liu J, Lu X, Golding BT, Griffin RJ, Hutton C, Newell DR, Ojo S, Watson AF, Zaytzev A, Zhao Y, Lunec J, Hardcastle IR..  (2013)  Diaryl- and triaryl-pyrrole derivatives: inhibitors of the MDM2-p53 and MDMX-p53 protein-protein interactions†Electronic supplementary information (ESI) available: Experimental details for compound synthesis, analytical data for all compounds and intermediates. Details for the biological evaluation. Further details for the modeling. Table of combustion analysis data. See DOI: 10.1039/c3md00161jClick here for additional data file.,  4  (9): [PMID:24078862] [10.1039/c3md00161j]

3. Aguilar A, Sun W, Liu L, Lu J, McEachern D, Bernard D, Deschamps JR, Wang S..  (2014)  Design of chemically stable, potent, and efficacious MDM2 inhibitors that exploit the retro-mannich ring-opening-cyclization reaction mechanism in spiro-oxindoles.,  57  (24): [PMID:25496041] [10.1021/jm501541j]

4.  (2014)  Spiro-oxindole MDM2 antagonists, 

5.  (2015)  Spiro-oxindole MDM2 antagonists, 

6. Hügel HM, de Silva NH, Siddiqui A, Blanch E, Lingham A..  (2021)  Natural spirocyclic alkaloids and polyphenols as multi target dementia leads.,  43  [PMID:34153839] [10.1016/j.bmc.2021.116270]

Source

Source(2):

• Scientific Literature
• BindingDB Database