2-(2-(4-(3,4-dichlorophenyl)thiazol-2-yl)hydrazono)-3-(2-nitrophenyl)propanoic acid

ID: ALA254578

Chembl Id: CHEMBL254578

Cas Number: 315706-13-9

PubChem CID: 6911989

Max Phase: Preclinical

Molecular Formula: C18H12Cl2N4O4S

Molecular Weight: 451.29

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(O)/C(Cc1ccccc1[N+](=O)[O-])=N\Nc1nc(-c2ccc(Cl)c(Cl)c2)cs1

Standard InChI:  InChI=1S/C18H12Cl2N4O4S/c19-12-6-5-10(7-13(12)20)15-9-29-18(21-15)23-22-14(17(25)26)8-11-3-1-2-4-16(11)24(27)28/h1-7,9H,8H2,(H,21,23)(H,25,26)/b22-14-

Standard InChI Key:  KFRKRECSIYXARE-HMAPJEAMSA-N

Alternative Forms

1. Parent:

   

   ALA254578

   H57Reu3dhp

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: 451.29

Molecular Weight (Monoisotopic): 449.9956

AlogP: 5.12

#Rotatable Bonds: 7

Polar Surface Area: 117.72

Molecular Species: ACID

HBA: 7

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 3.06

CX Basic pKa: 1.76

CX LogP: 6.28

CX LogD: 3.11

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.29

Np Likeness Score: -1.70

References

1. Wells JA, McClendon CL..  (2007)  Reaching for high-hanging fruit in drug discovery at protein-protein interfaces.,  450  (7172): [PMID:18075579] [10.1038/nature06526]

2. Mahalingam P, Takrouri K, Chen T, Sahoo R, Papadopoulos E, Chen L, Wagner G, Aktas BH, Halperin JA, Chorev M..  (2014)  Synthesis of rigidified eIF4E/eIF4G inhibitor-1 (4EGI-1) mimetic and their in vitro characterization as inhibitors of protein-protein interaction.,  57  (12): [PMID:24827861] [10.1021/jm401733v]

3. Takrouri K, Chen T, Papadopoulos E, Sahoo R, Kabha E, Chen H, Cantel S, Wagner G, Halperin JA, Aktas BH, Chorev M..  (2014)  Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein-protein interaction inhibitors.,  77  [PMID:24675136] [10.1016/j.ejmech.2014.03.034]

4. Cooper AB, Ciblat S, Shipps G, Levine J, Kostura M, Oza V, Constantineau-Forget L, Dery M, Grand-Maitre C, Bruneau-Latour N, Bellavance E, Patane M, Siddiqui A, Luther M..  (2017)  1-Thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives as antitumor agents.,  27  (18): [PMID:28844391] [10.1016/j.bmcl.2017.08.003]

5. David E Gordon, Gwendolyn M Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Kris M White, Matthew J O'Meara, Veronica V Rezelj, Jeffrey Z Guo, Danielle L Swaney, et al.  (2020)  A SARS-CoV-2 protein interaction map reveals targets for drug repurposing,  [PMID:32353859] [10.1038/s41586-020-2286-9]

6. Wang L, Guo C, Li X, Yu X, Li X, Xu K, Jiang B, Jia X, Li C, Shi D..  (2019)  Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment.,  177  [PMID:31132531] [10.1016/j.ejmech.2019.05.044]

7. Fischer PD, Papadopoulos E, Dempersmier JM, Wang ZF, Nowak RP, Donovan KA, Kalabathula J, Gorgulla C, Junghanns PPM, Kabha E, Dimitrakakis N, Petrov OI, Mitsiades C, Ducho C, Gelev V, Fischer ES, Wagner G, Arthanari H..  (2021)  A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders.,  219  [PMID:33892272] [10.1016/j.ejmech.2021.113435]

Source

Source(2):

• Scientific Literature
• SARS-CoV-2 Screening Data 2020-21