Detailed information for compound 240492
Basic information
Technical information
- TDR Targets ID: 240492
- Name: 5-chloro-6-N-[(2,5-dimethoxyphenyl)methyl]qui nazoline-2,4,6-triamine
- MW: 359.81 | Formula: C17H18ClN5O2
-
H donors: 3
H acceptors: 2
LogP: 2.89
Rotable bonds: 5
Rule of 5 violations (Lipinski): 1 - SMILES: COc1ccc(cc1CNc1ccc2c(c1Cl)c(N)nc(n2)N)OC
- InChi: 1S/C17H18ClN5O2/c1-24-10-3-6-13(25-2)9(7-10)8-21-12-5-4-11-14(15(12)18)16(19)23-17(20)22-11/h3-7,21H,8H2,1-2H3,(H4,19,20,22,23)
- InChiKey: ZQYDKYDSKVGDJP-UHFFFAOYSA-N
Network
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Synonyms
- 5-chloro-N6-[(2,5-dimethoxyphenyl)methyl]quinazoline-2,4,6-triamine
- (2,4-diamino-5-chloro-quinazolin-6-yl)-(2,5-dimethoxybenzyl)amine
- 2,4,6-Quinazolinetriamine, 5-chloro-N6-[(2,5-dimethoxyphenyl)methyl]-
- AIDS-030781
- AIDS030781
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Pneumocystis carinii | Dihydrofolate reductase | Starlite/ChEMBL | References |
| Rattus norvegicus | Dihydrofolate reductase | Starlite/ChEMBL | References |
| Toxoplasma gondii | bifunctional dihydrofolate reductase-thymidylate synthase | Starlite/ChEMBL | References |
| Homo sapiens | dihydrofolate reductase | Starlite/ChEMBL | References |
Predicted pathogen targets for this compound
By orthology
By sequence similarity to non orthologous known druggable targets
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Toxoplasma gondii | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0262031 | 0.279665 | 0.5 |
| Mycobacterium tuberculosis | Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) | 0.026048 | 0.276387 | 0.303636 |
| Mycobacterium ulcerans | dihydrofolate reductase DfrA | 0.026048 | 0.276387 | 0.276387 |
| Mycobacterium ulcerans | flavin-containing monoamine oxidase AofH | 0.0602733 | 1 | 1 |
| Loa Loa (eye worm) | dihydrofolate reductase | 0.026048 | 0.276387 | 1 |
| Plasmodium falciparum | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0262031 | 0.279665 | 0.5 |
| Mycobacterium tuberculosis | Probable flavin-containing monoamine oxidase AofH (amine oxidase) (MAO) | 0.0560287 | 0.910258 | 1 |
| Mycobacterium ulcerans | flavin-containing monoamine oxidase AofH | 0.0602733 | 1 | 1 |
| Echinococcus multilocularis | dihydrofolate reductase | 0.026048 | 0.276387 | 1 |
| Echinococcus granulosus | dihydrofolate reductase | 0.026048 | 0.276387 | 1 |
| Trypanosoma brucei | dihydrofolate reductase-thymidylate synthase | 0.0262031 | 0.279665 | 0.5 |
| Brugia malayi | dihydrofolate reductase family protein | 0.026048 | 0.276387 | 1 |
| Mycobacterium leprae | DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) | 0.026048 | 0.276387 | 1 |
| Trypanosoma cruzi | dihydrofolate reductase-thymidylate synthase | 0.0262031 | 0.279665 | 0.5 |
| Onchocerca volvulus | 0.0129756 | 0 | 0.5 | |
| Brugia malayi | Dihydrofolate reductase | 0.026048 | 0.276387 | 1 |
| Chlamydia trachomatis | dihydrofolate reductase | 0.026048 | 0.276387 | 0.5 |
| Plasmodium vivax | bifunctional dihydrofolate reductase-thymidylate synthase, putative | 0.0262031 | 0.279665 | 0.5 |
| Schistosoma mansoni | dihydrofolate reductase | 0.026048 | 0.276387 | 1 |
| Leishmania major | dihydrofolate reductase-thymidylate synthase | 0.0262031 | 0.279665 | 0.5 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| Activity (ADMET) | = 0 % | Toxicity in NMRI mice (Mus musculus) infected with Plasmodium berghei ANKA at 3 times 30 mg/kg, perorally measured up to 30 days postinfection | ChEMBL. | 20350951 |
| Activity (ADMET) | = 0 % | Toxicity in NMRI mice (Mus musculus) infected with Plasmodium berghei ANKA at 100 mg/kg, perorally administered as single dose measured up to 30 days postinfection | ChEMBL. | 20350951 |
| Activity (ADMET) | = 0 % | Toxicity in NMRI mice (Mus musculus) infected with Plasmodium berghei ANKA at 60 mg/kg, perorally administered as single dose measured up to 30 days postinfection | ChEMBL. | 20350951 |
| Activity (ADMET) | = 0 % | Toxicity in NMRI mice (Mus musculus) infected with Plasmodium berghei ANKA at 30 mg/kg, perorally administered as single dose measured up to 30 days postinfection | ChEMBL. | 20350951 |
| Activity (ADMET) | = 0 % | Toxicity in NMRI mice (Mus musculus) infected with Plasmodium berghei ANKA at 15 mg/kg, perorally administered as single dose measured up to 30 days postinfection | ChEMBL. | 20350951 |
| Activity (ADMET) | = 0 % | Toxicity in NMRI mice (Mus musculus) infected with Plasmodium berghei ANKA at 10 mg/kg, perorally administered as single dose measured up to 30 days postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 0 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as cure rate at 60 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 0 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as cure rate at 30 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 0 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as cure rate at 15 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 0 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as cure rate at 10 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 20 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as cure rate at 3 times 100 mg/kg, perorally measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (ADMET) | = 40 % | Toxicity in NMRI mice (Mus musculus) infected with Plasmodium berghei ANKA at 3 times 60 mg/kg, perorally measured up to 30 days postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 50 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as cure rate at 100 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 59 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as reduction in parasitemia at 10 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 60 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as cure rate at 3 times 60 mg/kg, perorally measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 73 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as reduction in parasitemia at 15 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (ADMET) | = 80 % | Toxicity in NMRI mice (Mus musculus) infected with Plasmodium berghei ANKA at 3 times 100 mg/kg, perorally measured up to 30 days postinfection | ChEMBL. | 20350951 |
| Activity (functional) | = 80 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as cure rate at 3 times 30 mg/kg, perorally measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | > 99.99 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as reduction in parasitemia at 3 times 100 mg/kg, perorally measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | > 99.99 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as reduction in parasitemia at 3 times 60 mg/kg, perorally measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | > 99.99 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as reduction in parasitemia at 3 times 30 mg/kg, perorally measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | > 99.99 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as reduction in parasitemia at 100 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | > 99.99 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as reduction in parasitemia at 60 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| Activity (functional) | > 99.99 % | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as reduction in parasitemia at 30 mg/kg, perorally administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| AUC (ADMET) | = 16990 ng.hr/ml | AUC (0 to 24 hrs) in NMRI mouse at 50 mg/kg, po | ChEMBL. | 20350951 |
| AUC (ADMET) | = 44.6 uM.hr | AUC in CD-1 mouse at 25 mg/kg, po | ChEMBL. | 20350951 |
| CL (ADMET) | = 51.06 ml/min.kg | Clearance in CD-1 mouse at 5 mg/kg, iv | ChEMBL. | 20350951 |
| Cmax (ADMET) | = 5.1 uM | Cmax in CD-1 mouse at 25 mg/kg, po | ChEMBL. | 20350951 |
| ED50 (functional) | = 7.2 mg kg-1 | Antimalarial activity against Plasmodium berghei ANKA infected in perorally dosed NMRI mice (Mus musculus) assessed as reduction in parasitemia administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| ED90 (functional) | = 12.4 mg kg-1 | Antimalarial activity against Plasmodium berghei ANKA infected in perorally dosed NMRI mice (Mus musculus) assessed as reduction in parasitemia administered as single dose measured on day 3 postinfection | ChEMBL. | 20350951 |
| F (ADMET) | = 100 % | Oral bioavailability in CD-1 mouse at 25 mg/kg | ChEMBL. | 20350951 |
| IC50 (functional) | = 4.48 nM | Antimalarial activity against pyrimethamine-resistant Plasmodium falciparum clinical isolate harboring S108N, C59R mutation in DHFR assessed as decrease in parasitaemia | ChEMBL. | 20350951 |
| IC50 (functional) | = 4.48 nM | Antimalarial activity against pyrimethamine-resistant Plasmodium falciparum clinical isolate harboring S108N, N51I mutation in DHFR assessed as decrease in parasitaemia | ChEMBL. | 20350951 |
| IC50 (functional) | = 7.61 nM | Antimalarial activity against pyrimethamine-resistant Plasmodium falciparum V1/S harboring S108N, N51I, C59R, I164L mutation in DHFR assessed as decrease in parasitaemia | ChEMBL. | 20350951 |
| IC50 (functional) | = 11.66 nM | Antimalarial activity against pyrimethamine-resistant Plasmodium falciparum clinical isolate harboring S108N, N51I, C59R mutation in DHFR assessed as decrease in parasitaemia | ChEMBL. | 20350951 |
| IC50 (functional) | = 0 uM | Antimicrobial activity against Cryptosporidium parvum | ChEMBL. | 20185316 |
| IC50 (binding) | = 0.017 uM | Inhibition of Dihydrofolate reductase of T. gondii | ChEMBL. | 7799402 |
| IC50 (binding) | = 0.017 uM | Inhibition of Dihydrofolate reductase of T. gondii | ChEMBL. | 7799402 |
| IC50 (binding) | = 0.028 uM | Inhibition of Dihydrofolate reductase (DHFR) of in rat liver | ChEMBL. | 7799402 |
| IC50 (binding) | = 0.028 uM | Inhibition of Dihydrofolate reductase (DHFR) of in rat liver | ChEMBL. | 7799402 |
| IC50 (binding) | = 0.053 uM | Inhibition of Dihydrofolate reductase of P. carinii | ChEMBL. | 7799402 |
| IC50 (binding) | = 0.053 uM | Inhibition of Dihydrofolate reductase of P. carinii | ChEMBL. | 7799402 |
| Ki (binding) | = 10.2 nM | Binding affinity to human recombinant DHFR expressed in Escherichia coli BL21(DE3) by competitive binding assay | ChEMBL. | 20350951 |
| Ratio (binding) | = 0.53 | Relative affinity for dihydrofolate reductase of rat liver and P. carinii | ChEMBL. | 7799402 |
| Ratio (binding) | = 1.6 | Relative affinity for dihydrofolate reductase of rat liver and T. gondii | ChEMBL. | 7799402 |
| Survival (functional) | = 6 day | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as survival rate at 15 mg/kg, perorally administered as single dose | ChEMBL. | 20350951 |
| Survival (functional) | = 6 day | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as survival rate at 10 mg/kg, perorally administered as single dose | ChEMBL. | 20350951 |
| Survival (functional) | = 8.1 day | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as survival rate at 30 mg/kg, perorally administered as single dose | ChEMBL. | 20350951 |
| Survival (functional) | = 12 day | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as survival rate at 60 mg/kg, perorally administered as single dose | ChEMBL. | 20350951 |
| Survival (functional) | = 23.4 day | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as survival rate at 100 mg/kg, perorally administered as single dose | ChEMBL. | 20350951 |
| Survival (functional) | = 28.4 day | Antimalarial activity against Plasmodium berghei ANKA infected in NMRI mice (Mus musculus) assessed as survival rate at 3 times 30 mg/kg, perorally | ChEMBL. | 20350951 |
| T1/2 (ADMET) | = 0.8 hr | Half life in CD-1 mouse at 5 mg/kg, iv | ChEMBL. | 20350951 |
| T1/2 (ADMET) | = 4.84 hr | Half life in CD-1 mouse at 25 mg/kg, po | ChEMBL. | 20350951 |
| Tmax (ADMET) | = 4 hr | Tmax in CD-1 mouse at 25 mg/kg, po | ChEMBL. | 20350951 |
| Vd (ADMET) | = 2.85 L/Kg | Volume of distribution in CD-1 mouse at 5 mg/kg, iv | ChEMBL. | 20350951 |
Phenotypes
Whole-cell/tissue/organism interactions
| Species name | Source | Reference | Is orphan |
|---|---|---|---|
| Cryptosporidium parvum | ChEMBL23 | 20185316 | |
| Plasmodium falciparum | ChEMBL23 | 20350951 |
Many chemical entities in TDR Targets come from high-throughput screenings with whole cells or tissue samples, and not all assayed compounds have been tested against a single a single target protein, probably because they get ruled out during screening process. Even if these compounds may have not been of interest in the original screening, they may come as interesting leads for other screening assays. Furthermore, we may be able to propose drug-target associations using chemical similarities and network patterns.
Annotated phenotypes:
We have no manually annotated phenotypes for this drug.
What does this mean? / Care to help?
In TDR Targets, information about phenotypes that are caused by
drugs, or by genetic manipulation of cells (e.g. gene knockouts or
knockdowns) is manually curated from the literature. These
descriptions help to describe the potential of the target for drug
development. If no information is available for this gene or if the
information is incomplete, this may mean that i) the papers
containing this information either appeared after the curation
effort for this organism was carried out or they were inadvertently
missed by curators; or that ii) the curation effort for this
organism has not yet started.
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.
External resources for this compound
- ChEMBL: CHEMBL138060
- PubChem: 461920
Bibliographic References
2 literature references were collected for this gene.
If you have references for this compound, please enter them in a user comment (below) or Contact us.