ID: ALA268584

Max Phase: Preclinical

Molecular Formula: C18H14N4O2S

Molecular Weight: 350.40

Molecule Type: Small molecule

Representations

Synonyms (3): TCMDC-137192 | GNF-Pf-2448 | TCMDC-137192
Synonyms from Alternative Forms(3):

Canonical SMILES:  Nc1nc(N)c2cc(S(=O)(=O)c3ccc4ccccc4c3)ccc2n1

Standard InChI:  InChI=1S/C18H14N4O2S/c19-17-15-10-14(7-8-16(15)21-18(20)22-17)25(23,24)13-6-5-11-3-1-2-4-12(11)9-13/h1-10H,(H4,19,20,21,22)

Standard InChI Key:  GBVQWZXJDIIUCC-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: 350.40

Molecular Weight (Monoisotopic): 350.0837

AlogP: 2.78

#Rotatable Bonds: 2

Polar Surface Area: 111.96

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 6

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 6.51

CX LogP: 2.98

CX LogD: 2.93

Aromatic Rings: 4

Heavy Atoms: 25

QED Weighted: 0.57

Np Likeness Score: -1.03

References

1. Ghose AK, Crippen GM..  (1983)  Combined distance geometry analysis of dihydrofolate reductase inhibition by quinazolines and triazines.,  26  (7): [PMID:6864738] [10.1021/jm00361a012]

2. Elslager EF, Colbry NL, Davoll J, Hutt MP, Johnson JL, Werbel LM..  (1984)  Folate antagonists. 22. Antimalarial and antibacterial effects of 2,4-diamino-6-quinazolinesulfonamides.,  27  (12): [PMID:6502605] [10.1021/jm00378a038]

3. Werbel LM, Degnan MJ..  (1987)  Synthesis and antimalarial and antitumor effects of 2-amino-4-(hydrazino and hydroxyamino)-6-[(aryl)thio]quinazolines.,  30  (11): [PMID:3669022] [10.1021/jm00394a038]

4. Crippen GM..  (1980)  Quantitative structure-activity relationships by distance geometry: systematic analysis of dihydrofolate reductase inhibitors.,  23  (6): [PMID:7392027] [10.1021/jm00180a004]

5. Battershell C, Malhotra D, Hopfinger AJ..  (1981)  Inhibition of dihydrofolate reductase: structure-activity correlations of quinazolines based upon molecular shape analysis.,  24  (7): [PMID:7277385] [10.1021/jm00139a009]

6. Ghose AK, Crippen GM..  (1982)  Quantitative structure-activity relationship by distance geometry: quinazolines as dihydrofolate reductase inhibitors.,  25  (8): [PMID:7120278] [10.1021/jm00350a003]

7. Ghose AK, Crippen GM..  (1984)  General distance geometry three-dimensional receptor model for diverse dihydrofolate reductase inhibitors.,  27  (7): [PMID:6737433] [10.1021/jm00373a016]

8. Gamo FJ, Sanz LM, Vidal J, de Cozar C, Alvarez E, Lavandera JL, Vanderwall DE, Green DV, Kumar V, Hasan S, Brown JR, Peishoff CE, Cardon LR, Garcia-Bustos JF..  (2010)  Thousands of chemical starting points for antimalarial lead identification.,  465  (7296): [PMID:20485427] [10.1038/nature09107]

9. 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]

10. PubChem BioAssay data set, 

11. PubChem BioAssay data set, 

12. Elslager EF, Hutt MP, Jacob P, Johnson J, Temporelli B, Werbel LM, Worth DF, Rane L..  (1979)  Folate antagonists. 15. 2,3-Diamino-6-(2-naphthylsulfonyl)quinazoline and related 2,4-diamino-6-[(phenyl and naphthyl)sulfinyl and sulfonyl]quinazolines, a potent new class of antimetabolites with phenomenal antimalarial activity.,  22  (10): [PMID:117107] [10.1021/jm00196a019]

13. Kinnamon KE, Steck EA, Hanson WL, Chapman WL..  (1977)  In search of anti-Trypanosoma cruzi drugs: new leads from a mouse model.,  20  (6): [PMID:69024] [10.1021/jm00216a001]

14. Genther CS, Smith CS..  (1977)  Antifolate studies. Activities of 40 potential antimalarial compounds against sensitive and chlorguanide triazine resistant strains of folate-requiring bacteria and Escherichia coli.,  20  (2): [PMID:137981] [10.1021/jm00212a010]

15. Fukunaga JY, Hansch C, Steller EE..  (1976)  Inhibition of dihydrofolate reductase. Structure-activity correlations of quinazolines.,  19  (5): [PMID:1271401] [10.1021/jm00227a006]

16. Hansch C, Fukunaga JY, Jow PY..  (1977)  Quantitative structure-activity relationships of antimalarial and dihydrofolate reductase inhibition by quinazolines and 5-substituted benzyl-2,4-diaminopyrimidines.,  20  (1): [PMID:319234] [10.1021/jm00211a020]

17. St. Jude Leishmania screening dataset.,  [10.6019/CHEMBL3433997]

Source

Source(5):

• Scientific Literature
• GSK Malaria Screening
• Novartis Malaria Screening
• PubChem BioAssays
• St Jude Leishmania Screening