ID: ALA278847

Max Phase: Preclinical

Molecular Formula: C12H13ClN4

Molecular Weight: 248.72

Molecule Type: Small molecule

Representations

Synonyms (2): TCMDC-137371 | TCMDC-137371
Synonyms from Alternative Forms(2):

Canonical SMILES:  CCc1nc(N)nc(N)c1-c1cccc(Cl)c1

Standard InChI:  InChI=1S/C12H13ClN4/c1-2-9-10(11(14)17-12(15)16-9)7-4-3-5-8(13)6-7/h3-6H,2H2,1H3,(H4,14,15,16,17)

Standard InChI Key:  KYIIICAIZHTXJE-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: 248.72

Molecular Weight (Monoisotopic): 248.0829

AlogP: 2.52

#Rotatable Bonds: 2

Polar Surface Area: 77.82

Molecular Species: NEUTRAL

HBA: 4

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 7.77

CX LogP: 2.75

CX LogD: 2.24

Aromatic Rings: 2

Heavy Atoms: 17

QED Weighted: 0.86

Np Likeness Score: -1.07

References

1. Tarnchompoo B, Sirichaiwat C, Phupong W, Intaraudom C, Sirawaraporn W, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y..  (2002)  Development of 2,4-diaminopyrimidines as antimalarials based on inhibition of the S108N and C59R+S108N mutants of dihydrofolate reductase from pyrimethamine-resistant Plasmodium falciparum.,  45  (6): [PMID:11881993] [10.1021/jm010131q]

2. McKie JH, Douglas KT, Chan C, Roser SA, Yates R, Read M, Hyde JE, Dascombe MJ, Yuthavong Y, Sirawaraporn W..  (1998)  Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria.,  41  (9): [PMID:9554869] [10.1021/jm970845u]

3. Kamchonwongpaisan S, Quarrell R, Charoensetakul N, Ponsinet R, Vilaivan T, Vanichtanankul J, Tarnchompoo B, Sirawaraporn W, Lowe G, Yuthavong Y..  (2004)  Inhibitors of multiple mutants of Plasmodium falciparum dihydrofolate reductase and their antimalarial activities.,  47  (3): [PMID:14736247] [10.1021/jm030165t]

4. Parenti MD, Pacchioni S, Ferrari AM, Rastelli G..  (2004)  Three-dimensional quantitative structure-activity relationship analysis of a set of Plasmodium falciparum dihydrofolate reductase inhibitors using a pharmacophore generation approach.,  47  (17): [PMID:15293997] [10.1021/jm040769c]

5. El-Hamamsy MH, Smith AW, Thompson AS, Threadgill MD..  (2007)  Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis.,  15  (13): [PMID:17451962] [10.1016/j.bmc.2007.04.011]

6. 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]

7. 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]

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

9. Tarnchompoo B, Chitnumsub P, Jaruwat A, Shaw PJ, Vanichtanankul J, Poen S, Rattanajak R, Wongsombat C, Tonsomboon A, Decharuangsilp S, Anukunwithaya T, Arwon U, Kamchonwongpaisan S, Yuthavong Y..  (2018)  Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance.,  9  (12): [PMID:30613332] [10.1021/acsmedchemlett.8b00389]

10. Saepua S, Sadorn K, Vanichtanankul J, Anukunwithaya T, Rattanajak R, Vitsupakorn D, Kamchonwongpaisan S, Yuthavong Y, Thongpanchang C..  (2019)  6-Hydrophobic aromatic substituent pyrimethamine analogues as potential antimalarials for pyrimethamine-resistant Plasmodium falciparum.,  27  (24): [PMID:31685330] [10.1016/j.bmc.2019.115158]

Source

Source(3):

• Scientific Literature
• GSK Malaria Screening
• St Jude Leishmania Screening