ID: ALA274031

Max Phase: Preclinical

Molecular Formula: C18H18N4O

Molecular Weight: 306.37

Molecule Type: Small molecule

Representations

Canonical SMILES:  Nc1ncc(Cc2cccc(OCc3ccccc3)c2)c(N)n1

Standard InChI:  InChI=1S/C18H18N4O/c19-17-15(11-21-18(20)22-17)9-14-7-4-8-16(10-14)23-12-13-5-2-1-3-6-13/h1-8,10-11H,9,12H2,(H4,19,20,21,22)

Standard InChI Key:  PUMGLGGVAIIWCB-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: 306.37

Molecular Weight (Monoisotopic): 306.1481

AlogP: 2.81

#Rotatable Bonds: 5

Polar Surface Area: 87.05

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 7.16

CX LogP: 3.32

CX LogD: 3.14

Aromatic Rings: 3

Heavy Atoms: 23

QED Weighted: 0.76

Np Likeness Score: -0.52

References

1. Dietrich SW, Blaney JM, Reynolds MA, Jow PY, Hansch C..  (1980)  Quantitative structure-selectivity relationships. Comparison of the inhibition of Escherichia coli and bovine liver dihydrofolate reductase by 5-(substituted-benzyl)-2,4-diaminopyrimidines.,  23  (11): [PMID:7005446] [10.1021/jm00185a011]

2. Doweyko AM..  (1988)  The hypothetical active site lattice. An approach to modelling active sites from data on inhibitor molecules.,  31  (7): [PMID:3290487] [10.1021/jm00402a025]

3. Selassie CD, Fang ZX, Li RL, Hansch C, Debnath G, Klein TE, Langridge R, Kaufman BT..  (1989)  On the structure selectivity problem in drug design. A comparative study of benzylpyrimidine inhibition of vertebrate and bacterial dihydrofolate reductase via molecular graphics and quantitative structure-activity relationships.,  32  (8): [PMID:2502631] [10.1021/jm00128a035]

4. Loukas YL..  (2001)  Adaptive neuro-fuzzy inference system: an instant and architecture-free predictor for improved QSAR studies.,  44  (17): [PMID:11495588] [10.1021/jm000226c]

5. So SS, Richards WG..  (1992)  Application of neural networks: quantitative structure-activity relationships of the derivatives of 2,4-diamino-5-(substituted-benzyl)pyrimidines as DHFR inhibitors.,  35  (17): [PMID:1507206] [10.1021/jm00095a016]

6. Ghose AK, Crippen GM..  (1985)  Use of physicochemical parameters in distance geometry and related three-dimensional quantitative structure-activity relationships: a demonstration using Escherichia coli dihydrofolate reductase inhibitors.,  28  (3): [PMID:3882967] [10.1021/jm00381a013]

7. Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y..  (2004)  Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum.,  47  (2): [PMID:14711307] [10.1021/jm0303352]

8. Li RL, Poe M..  (1988)  Quantitative structure-activity relationships for the inhibition of Escherichia coli dihydrofolate reductase by 5-(substituted benzyl)-2,4-diaminopyrimidines.,  31  (2): [PMID:3276891] [10.1021/jm00397a017]

9. Chowdhury SF, Villamor VB, Guerrero RH, Leal I, Brun R, Croft SL, Goodman JM, Maes L, Ruiz-Perez LM, Pacanowska DG, Gilbert IH..  (1999)  Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase.,  42  (21): [PMID:10543874] [10.1021/jm981130+]

10. Li R, Hansch C, Kaufman BT..  (1982)  A comparison of the inhibitory action of 5-(substituted-benzyl)-2,4-diaminopyrimidines on dihydrofolate reductase from chicken liver with that from bovine liver.,  25  (4): [PMID:7069722] [10.1021/jm00346a020]

11. Selassie CD, Li R, Hansch C, Khwaja TA, Dias CB..  (1982)  Inhibition by 5-(substituted-benzyl)-2,4-diaminopyrimidines of murine tumor (L5178Y) cell cultures sensitive to and resistant to methotrexate. Further evidence for the sensitivity of resistant cells to hydrophobic drugs.,  25  (5): [PMID:7086836] [10.1021/jm00347a007]

12. Selassie CD, Li RL, Poe M, Hansch C..  (1991)  On the optimization of hydrophobic and hydrophilic substituent interactions of 2,4-diamino-5-(substituted-benzyl)pyrimidines with dihydrofolate reductase.,  34  (1): [PMID:1899453] [10.1021/jm00105a008]

13. Li RL, Dietrich SW, Hansch C..  (1981)  Quantitative structure-selectivity relationships. Comparison of the inhibition of Escherichia coli and bovine liver dihydrofolate reductase by 5-(substituted-benzyl)-2,4-diaminopyrimidines.,  24  (5): [PMID:7017146] [10.1021/jm00137a012]

14. Selassie CD, Fang ZX, Li RL, Hansch C, Klein T, Langridge R, Kaufman BT..  (1986)  Inhibition of chicken liver dihydrofolate reductase by 5-(substituted benzyl)-2,4-diaminopyrimidines. A quantitative structure-activity relationship and graphics analysis.,  29  (5): [PMID:3701780] [10.1021/jm00155a006]

15. Hansch C, Li R, Blaney JM, Langridge R..  (1982)  Comparison of the inhibition of Escherichia coli and Lactobacillus casei dihydrofolate reductase by 2,4-diamino-5-(substituted-benzyl)pyrimidines: quantitative structure-activity relationships, X-ray crystallography, and computer graphics in structure-activity analysis.,  25  (7): [PMID:6809941] [10.1021/jm00349a003]

16. Hopfinger AJ..  (1981)  Inhibition of dihydrofolate reductase: structure-activity correlations of 2,4-diamino-5-benzylpyrimidines based upon molecular shape analysis.,  24  (7): [PMID:7277386] [10.1021/jm00139a010]

17. Hopfinger AJ..  (1983)  Theory and application of molecular potential energy fields in molecular shape analysis: a quantitative structure--activity relationship study of 2,4-diamino-5-benzylpyrimidines as dihydrofolate reductase inhibitors.,  26  (7): [PMID:6345782] [10.1021/jm00361a011]

18. Prado-Prado FJ, García-Mera X, González-Díaz H..  (2010)  Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.,  18  (6): [PMID:20185316] [10.1016/j.bmc.2010.01.068]

19. Blaney JM, Dietrich SW, Reynolds MA, Hansch C..  (1979)  Quantitative structure-activity relationship of 5-(X-benzyl)-2,4-diaminopyrimidines inhibiting bovine liver dihydrofolate reductase.,  22  (6): [PMID:458817] [10.1021/jm00192a003]

Source

Source(1):

• Scientific Literature