ID: ALA579731

Max Phase: Preclinical

Molecular Formula: C26H27ClN4

Molecular Weight: 430.98

Molecule Type: Small molecule

Representations

Synonyms (1): GNF-Pf-3356
Synonyms from Alternative Forms(1):

Canonical SMILES:  CCN(CC)CCNc1nc(/C=C/c2ccc(Cl)cc2)nc2cc3ccccc3cc12

Standard InChI:  InChI=1S/C26H27ClN4/c1-3-31(4-2)16-15-28-26-23-17-20-7-5-6-8-21(20)18-24(23)29-25(30-26)14-11-19-9-12-22(27)13-10-19/h5-14,17-18H,3-4,15-16H2,1-2H3,(H,28,29,30)/b14-11+

Standard InChI Key:  MSOORHLGOVMZQM-SDNWHVSQSA-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: 430.98

Molecular Weight (Monoisotopic): 430.1924

AlogP: 6.36

#Rotatable Bonds: 8

Polar Surface Area: 41.05

Molecular Species: BASE

HBA: 4

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa:

CX Basic pKa: 9.29

CX LogP: 6.99

CX LogD: 5.10

Aromatic Rings: 4

Heavy Atoms: 31

QED Weighted: 0.33

Np Likeness Score: -1.05

References

1. Plouffe D, Brinker A, McNamara C, Henson K, Kato N, Kuhen K, Nagle A, Adrián F, Matzen JT, Anderson P, Nam TG, Gray NS, Chatterjee A, Janes J, Yan SF, Trager R, Caldwell JS, Schultz PG, Zhou Y, Winzeler EA..  (2008)  In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen.,  105  (26): [PMID:18579783] [10.1073/pnas.0802982105]

2. Keffer JL, Huecas S, Hammill JT, Wipf P, Andreu JM, Bewley CA..  (2013)  Chrysophaentins are competitive inhibitors of FtsZ and inhibit Z-ring formation in live bacteria.,  21  (18): [PMID:23932448] [10.1016/j.bmc.2013.07.033]

3. Nepomuceno GM, Chan KM, Huynh V, Martin KS, Moore JT, O'Brien TE, Pollo LA, Sarabia FJ, Tadeus C, Yao Z, Anderson DE, Ames JB, Shaw JT..  (2015)  Synthesis and Evaluation of Quinazolines as Inhibitors of the Bacterial Cell Division Protein FtsZ.,  6  (3): [PMID:25815151] [10.1021/ml500497s]

4. Matsui T, Lallo S, Nisa K, Morita H..  (2017)  Filamenting temperature-sensitive mutant Z inhibitors from Glycyrrhiza glabra and their inhibitory mode of action.,  27  (6): [PMID:28196701] [10.1016/j.bmcl.2017.01.095]

5. Zhou D, Springer MZ, Xu D, Liu D, Hudmon A, Macleod KF, Meroueh SO..  (2017)  Small molecules inhibit STAT3 activation, autophagy, and cancer cell anchorage-independent growth.,  25  (12): [PMID:28438385] [10.1016/j.bmc.2017.03.048]

6. Baska F, Sipos A, Őrfi Z, Nemes Z, Dobos J, Szántai-Kis C, Szabó E, Szénási G, Dézsi L, Hamar P, Cserepes MT, Tóvári J, Garamvölgyi R, Krekó M, Őrfi L..  (2019)  Discovery and development of extreme selective inhibitors of the ITD and D835Y mutant FLT3 kinases.,  184  [PMID:31614258] [10.1016/j.ejmech.2019.111710]

7. Hurley KA, Santos TM, Nepomuceno GM, Huynh V, Shaw JT, Weibel DB..  (2016)  Targeting the Bacterial Division Protein FtsZ.,  59  (15): [PMID:26756351] [10.1021/acs.jmedchem.5b01098]

8. Huecas S, Araújo-Bazán L, Ruiz FM, Ruiz-Ávila LB, Martínez RF, Escobar-Peña A, Artola M, Vázquez-Villa H, Martín-Fontecha M, Fernández-Tornero C, López-Rodríguez ML, Andreu JM..  (2021)  Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery.,  64  (9.0): [PMID:33908781] [10.1021/acs.jmedchem.0c02207]

9. Buroni S, Makarov V, Scoffone VC, Trespidi G, Riccardi G, Chiarelli LR..  (2020)  The cell division protein FtsZ as a cellular target to hit cystic fibrosis pathogens.,  190  [PMID:32066012] [10.1016/j.ejmech.2020.112132]

Source

Source(2):

• Scientific Literature
• Novartis Malaria Screening