ID: ALA307767

Max Phase: Preclinical

Molecular Formula: C18H26N10O3

Molecular Weight: 430.47

Molecule Type: Small molecule

Representations

Synonyms (1): Netropsin
Synonyms from Alternative Forms(1):

Canonical SMILES:  Cn1cc(NC(=O)c2cc(NC(=O)CNC(=N)N)cn2C)cc1C(=O)NCCC(=N)N

Standard InChI:  InChI=1S/C18H26N10O3/c1-27-9-11(6-12(27)16(30)23-4-3-14(19)20)26-17(31)13-5-10(8-28(13)2)25-15(29)7-24-18(21)22/h5-6,8-9H,3-4,7H2,1-2H3,(H3,19,20)(H,23,30)(H,25,29)(H,26,31)(H4,21,22,24)

Standard InChI Key:  IDBIFFKSXLYUOT-UHFFFAOYSA-N

Molecule Features

Natural Product: Yes

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: 430.47

Molecular Weight (Monoisotopic): 430.2189

AlogP: -0.91

#Rotatable Bonds: 9

Polar Surface Area: 208.93

Molecular Species: BASE

HBA: 7

HBD: 8

#RO5 Violations: 1

HBA (Lipinski): 13

HBD (Lipinski): 10

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 13.08

CX Basic pKa: 12.45

CX LogP: -2.81

CX LogD: -7.27

Aromatic Rings: 2

Heavy Atoms: 31

QED Weighted: 0.19

Np Likeness Score: -0.77

References

1. Debart F, Periguad C, Gosselin G, Mrani D, Rayner B, Le Ber P, Auclair C, Balzarini J, De Clercq E, Paoletti C..  (1989)  Synthesis, DNA binding, and biological evaluation of synthetic precursors and novel analogues of netropsin.,  32  (5): [PMID:2540332] [10.1021/jm00125a024]

2. Fairley TA, Tidwell RR, Donkor I, Naiman NA, Ohemeng KA, Lombardy RJ, Bentley JA, Cory M..  (1993)  Structure, DNA minor groove binding, and base pair specificity of alkyl- and aryl-linked bis(amidinobenzimidazoles) and bis(amidinoindoles).,  36  (12): [PMID:8510102] [10.1021/jm00064a008]

3. Zhao R, al-Said NH, Sternbach DL, Lown JW..  (1997)  Camptothecin and minor-groove binder hybrid molecules: synthesis, inhibition of topoisomerase I, and anticancer cytotoxicity in vitro.,  40  (2): [PMID:9003520] [10.1021/jm9605804]

4. Lown JW, Krowicki K, Balzarini J, Newman RA, De Clercq E..  (1989)  Novel linked antiviral and antitumor agents related to netropsin and distamycin: synthesis and biological evaluation.,  32  (10): [PMID:2552118] [10.1021/jm00130a024]

5. Fishleigh RV, Fox KR, Khalaf AI, Pitt AR, Scobie M, Suckling CJ, Urwin J, Waigh RD, Young SC..  (2000)  DNA binding, solubility, and partitioning characteristics of extended lexitropsins.,  43  (17): [PMID:10966744] [10.1021/jm990620e]

6. Cory M, Tidwell RR, Fairley TA..  (1992)  Structure and DNA binding activity of analogues of 1,5-bis(4-amidinophenoxy)pentane (pentamidine),  35  (3): [PMID:1738139] [10.1021/jm00081a003]

7. Schneider HJ..  (2008)  Ligand binding to nucleic acids and proteins: Does selectivity increase with strength?,  43  (11): [PMID:18403056] [10.1016/j.ejmech.2008.02.011]

8. Wolter FE, Molinari L, Socher ER, Schneider K, Nicholson G, Beil W, Seitz O, Süssmuth RD..  (2009)  Synthesis and evaluation of a netropsin-proximicin-hybrid library for DNA binding and cytotoxicity.,  19  (14): [PMID:19427785] [10.1016/j.bmcl.2009.04.042]

9. Hauschild KE, Stover JS, Boger DL, Ansari AZ..  (2009)  CSI-FID: high throughput label-free detection of DNA binding molecules.,  19  (14): [PMID:19435662] [10.1016/j.bmcl.2009.04.097]

10. Nagle PS, Rodriguez F, Kahvedzić A, Quinn SJ, Rozas I..  (2009)  Asymmetrical diaromatic guanidinium/2-aminoimidazolinium derivatives: synthesis and DNA affinity.,  52  (22): [PMID:19873979] [10.1021/jm901017t]

11. Glass LS, Bapat A, Kelley MR, Georgiadis MM, Long EC..  (2010)  Semi-automated high-throughput fluorescent intercalator displacement-based discovery of cytotoxic DNA binding agents from a large compound library.,  20  (5): [PMID:20144868] [10.1016/j.bmcl.2010.01.033]

12. Zołek T, Maciejewska D..  (2010)  Theoretical models of pentamidine analogs activity based on their DNA minor groove complexes.,  45  (5): [PMID:20153561] [10.1016/j.ejmech.2010.01.047]

13. Zhang R, Wu X, Guziec LJ, Guziec FS, Chee GL, Yalowich JC, Hasinoff BB..  (2010)  Design, synthesis and biological evaluation of a novel series of anthrapyrazoles linked with netropsin-like oligopyrrole carboxamides as anticancer agents.,  18  (11): [PMID:20471276] [10.1016/j.bmc.2010.04.028]

14. Brucoli F, Natoli A, Marimuthu P, Borrello MT, Stapleton P, Gibbons S, Schätzlein A..  (2012)  Efficient synthesis and biological evaluation of proximicins A, B and C.,  20  (6): [PMID:22364744] [10.1016/j.bmc.2012.01.043]

15. Hassan GS, El-Messery SM, Al-Omary FA, El-Subbagh HI..  (2012)  Substituted thiazoles VII. Synthesis and antitumor activity of certain 2-(substituted amino)-4-phenyl-1,3-thiazole analogs.,  22  (20): [PMID:22995621] [10.1016/j.bmcl.2012.08.095]

16. Zhu W, Wang Y, Li K, Gao J, Huang CH, Chen CC, Ko TP, Zhang Y, Guo RT, Oldfield E..  (2015)  Antibacterial drug leads: DNA and enzyme multitargeting.,  58  (3): [PMID:25574764] [10.1021/jm501449u]

17. Picconi P, Hind C, Jamshidi S, Nahar K, Clifford M, Wand ME, Sutton JM, Rahman KM..  (2017)  Triaryl Benzimidazoles as a New Class of Antibacterial Agents against Resistant Pathogenic Microorganisms.,  60  (14): [PMID:28650661] [10.1021/acs.jmedchem.7b00108]

18. Shaktah R,Vardanyan L,David E,Aleman A,Orr D,Shaktah LA,Tamae D,Minehan T.  (2020)  Synthesis and Stereochemical Assignment of Conioidine A: DNA- and HSA-Binding Studies of the Four Diastereomers.,  83  (10): [PMID:33034450] [10.1021/acs.jnatprod.0c00871]

Source

Source(1):

• Scientific Literature