ID: ALA281812

Max Phase: Preclinical

Molecular Formula: C11H12Cl2N4O5

Molecular Weight: 351.15

Molecule Type: Small molecule

Representations

Synonyms (1): SN-23862
Synonyms from Alternative Forms(1):

Canonical SMILES:  NC(=O)c1cc(N(CCCl)CCCl)c([N+](=O)[O-])cc1[N+](=O)[O-]

Standard InChI:  InChI=1S/C11H12Cl2N4O5/c12-1-3-15(4-2-13)9-5-7(11(14)18)8(16(19)20)6-10(9)17(21)22/h5-6H,1-4H2,(H2,14,18)

Standard InChI Key:  DQMALWRRERBILB-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: 351.15

Molecular Weight (Monoisotopic): 350.0185

AlogP: 1.89

#Rotatable Bonds: 8

Polar Surface Area: 132.61

Molecular Species: NEUTRAL

HBA: 6

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 9

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 10.98

CX Basic pKa:

CX LogP: 2.14

CX LogD: 2.14

Aromatic Rings: 1

Heavy Atoms: 22

QED Weighted: 0.43

Np Likeness Score: -0.98

References

1. Palmer BD, van Zijl P, Denny WA, Wilson WR..  (1995)  Reductive chemistry of the novel hypoxia-selective cytotoxin 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide.,  38  (7): [PMID:7707325] [10.1021/jm00007a019]

2. Friedlos F, Denny WA, Palmer BD, Springer CJ..  (1997)  Mustard prodrugs for activation by Escherichia coli nitroreductase in gene-directed enzyme prodrug therapy.,  40  (8): [PMID:9111301] [10.1021/jm960794l]

3. Lee HH, Palmer BD, Wilson WR, Denny WA..  (1998)  Synthesis and hypoxia-selective cytotoxicity of a 2-nitroimidazole mustard.,  8  (13): [PMID:9873426] [10.1016/s0960-894x(98)00305-9]

4. Palmer BD, Wilson WR, Atwell GJ, Schultz D, Xu XZ, Denny WA..  (1994)  Hypoxia-selective antitumor agents. 9. Structure-activity relationships for hypoxia-selective cytotoxicity among analogues of 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide.,  37  (14): [PMID:8035424] [10.1021/jm00040a009]

5. Palmer BD, Wilson WR, Anderson RF, Boyd M, Denny WA..  (1996)  Hypoxia-selective antitumor agents. 14. Synthesis and hypoxic cell cytotoxicity of regioisomers of the hypoxia-selective cytotoxin 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide.,  39  (13): [PMID:8691449] [10.1021/jm960057p]

6. Palmer BD, Wilson WR, Cliffe S, Denny WA..  (1992)  Hypoxia-selective antitumor agents. 5. Synthesis of water-soluble nitroaniline mustards with selective cytotoxicity for hypoxic mammalian cells.,  35  (17): [PMID:1507207] [10.1021/jm00095a018]

7. Parkinson GN, Skelly JV, Neidle S..  (2000)  Crystal structure of FMN-dependent nitroreductase from Escherichia coli B: a prodrug-activating enzyme.,  43  (20): [PMID:11020276] [10.1021/jm000159m]

8. Atwell GJ, Yang S, Pruijn FB, Pullen SM, Hogg A, Patterson AV, Wilson WR, Denny WA..  (2007)  Synthesis and structure-activity relationships for 2,4-dinitrobenzamide-5-mustards as prodrugs for the Escherichia coli nfsB nitroreductase in gene therapy.,  50  (6): [PMID:17326614] [10.1021/jm061062o]

9. Çelik A, Yetiş G..  (2012)  An unusually cold active nitroreductase for prodrug activations.,  20  (11): [PMID:22546205] [10.1016/j.bmc.2012.04.004]

10. Tokay E, Güngör T, Hacıoğlu N, Önder FC, Gülhan ÜG, Tok TT, Çelik A, Ay M, Köçkar F..  (2020)  Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.,  187  [PMID:31841727] [10.1016/j.ejmech.2019.111937]

11. Güngör T, Önder FC, Tokay E, Gülhan ÜG, Hacıoğlu N, Tok TT, Çelik A, Köçkar F, Ay M..  (2019)  PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells.,  171  [PMID:30928710] [10.1016/j.ejmech.2019.03.035]

Source

Source(1):

• Scientific Literature