Detailed information for compound 314198

Basic information

Technical information
  • TDR Targets ID: 314198
  • Name: 2-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)pi perazin-1-yl]naphthalene-1,4-dione
  • MW: 445.471 | Formula: C24H23N5O4
  • H donors: 1 H acceptors: 4 LogP: 2.92 Rotable bonds: 4
    Rule of 5 violations (Lipinski): 1
  • SMILES: COc1cc2nc(nc(c2cc1OC)N)N1CCN(CC1)C1=CC(=O)c2c(C1=O)cccc2
  • InChi: 1S/C24H23N5O4/c1-32-20-11-16-17(12-21(20)33-2)26-24(27-23(16)25)29-9-7-28(8-10-29)18-13-19(30)14-5-3-4-6-15(14)22(18)31/h3-6,11-13H,7-10H2,1-2H3,(H2,25,26,27)
  • InChiKey: WDWPULBPXBZDDC-UHFFFAOYSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 2-[4-(4-amino-6,7-dimethoxy-quinazolin-2-yl)piperazin-1-yl]naphthalene-1,4-dione
  • 2-[4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-1-piperazinyl]naphthalene-1,4-dione
  • 2-[4-(4-azanyl-6,7-dimethoxy-quinazolin-2-yl)piperazin-1-yl]naphthalene-1,4-dione
  • 2-[4-(4-amino-6,7-dimethoxy-quinazolin-2-yl)piperazino]-1,4-naphthoquinone
  • 2-[4-(4-amino-6,7-dimethoxy-quinazolin-2-yl)piperazin-1-yl]-1,4-naphthoquinone

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Rattus norvegicus Alpha-1b adrenergic receptor Starlite/ChEMBL References
Homo sapiens adrenoceptor alpha 1A Starlite/ChEMBL References
Rattus norvegicus Alpha-1d adrenergic receptor Starlite/ChEMBL References
Trypanosoma cruzi trypanothione reductase, putative Starlite/ChEMBL References
Homo sapiens adrenoceptor alpha 1B Starlite/ChEMBL References
Rattus norvegicus Alpha-1a adrenergic receptor Starlite/ChEMBL References
Homo sapiens adrenoceptor alpha 1D Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Plasmodium berghei glutathione reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Schistosoma mansoni amine GPCR Get druggable targets OG5_128924 All targets in OG5_128924
Plasmodium knowlesi glutathione reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Mycobacterium tuberculosis NADPH-dependent mycothiol reductase Mtr Get druggable targets OG5_126785 All targets in OG5_126785
Plasmodium berghei thioredoxin reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Candida albicans similar to S. cerevisiae GLR1 (YPL091W) glutathione oxidoreductase Get druggable targets OG5_126785 All targets in OG5_126785
Loa Loa (eye worm) glutathione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Trypanosoma brucei gambiense trypanothione reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Plasmodium vivax thioredoxin reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Echinococcus granulosus thioredoxin glutathione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Trypanosoma cruzi trypanothione reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Candida albicans similar to S. cerevisiae GLR1 (YPL091W) glutathione oxidoreductase Get druggable targets OG5_126785 All targets in OG5_126785
Schistosoma japonicum ko:K04135 adrenergic receptor, alpha 1a, putative Get druggable targets OG5_128924 All targets in OG5_128924
Plasmodium yoelii thioredoxin reductase Get druggable targets OG5_126785 All targets in OG5_126785
Plasmodium knowlesi thioredoxin reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Plasmodium falciparum thioredoxin reductase Get druggable targets OG5_126785 All targets in OG5_126785
Brugia malayi glutathione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Leishmania infantum trypanothione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Brugia malayi Thioredoxin reductase Get druggable targets OG5_126785 All targets in OG5_126785
Neospora caninum MGC84926 protein, related Get druggable targets OG5_126785 All targets in OG5_126785
Leishmania donovani trypanothione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Toxoplasma gondii thioredoxin reductase Get druggable targets OG5_126785 All targets in OG5_126785
Loa Loa (eye worm) thioredoxin reductase Get druggable targets OG5_126785 All targets in OG5_126785
Echinococcus multilocularis thioredoxin glutathione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Plasmodium vivax glutathione reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Cryptosporidium parvum thioredoxin reductase 1 Get druggable targets OG5_126785 All targets in OG5_126785
Leishmania major trypanothione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Plasmodium yoelii glutathione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Theileria parva thioredoxin reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Trypanosoma brucei trypanothione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Trypanosoma congolense trypanothione reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Schistosoma japonicum ko:K00384 thioredoxin reductase (NADPH) [EC1.8.1.9], putative Get druggable targets OG5_126785 All targets in OG5_126785
Plasmodium falciparum glutathione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Babesia bovis thiodoxin reductase, putative Get druggable targets OG5_126785 All targets in OG5_126785
Cryptosporidium hominis thioredoxin reductase Get druggable targets OG5_126785 All targets in OG5_126785
Schistosoma japonicum Alpha-1D adrenergic receptor, putative Get druggable targets OG5_128924 All targets in OG5_128924
Leishmania braziliensis trypanothione reductase Get druggable targets OG5_126785 All targets in OG5_126785
Neospora caninum Glutathione reductase, related Get druggable targets OG5_126785 All targets in OG5_126785
Leishmania mexicana trypanothione reductase Get druggable targets OG5_126785 All targets in OG5_126785
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Schistosoma japonicum ko:K04136 adrenergic receptor, alpha 1b, putative Alpha-1a adrenergic receptor   466 aa 386 aa 31.6 %
Plasmodium falciparum dihydrolipoyl dehydrogenase, apicoplast trypanothione reductase, putative 492 aa 548 aa 21.5 %
Echinococcus granulosus rhodopsin orphan GPCR Alpha-1a adrenergic receptor   466 aa 418 aa 20.3 %
Echinococcus granulosus g protein coupled receptor Alpha-1a adrenergic receptor   466 aa 399 aa 20.8 %
Schistosoma japonicum ko:K04135 adrenergic receptor, alpha 1a, putative Alpha-1a adrenergic receptor   466 aa 443 aa 31.2 %
Echinococcus multilocularis neuropeptide Y receptor Alpha-1a adrenergic receptor   466 aa 419 aa 19.6 %
Echinococcus granulosus g protein coupled receptor Alpha-1a adrenergic receptor   466 aa 414 aa 20.5 %
Echinococcus multilocularis g protein coupled receptor Alpha-1a adrenergic receptor   466 aa 398 aa 21.4 %
Echinococcus multilocularis g protein coupled receptor Alpha-1a adrenergic receptor   466 aa 414 aa 20.3 %
Schistosoma japonicum FMRFamide receptor, putative Alpha-1a adrenergic receptor   466 aa 374 aa 19.5 %
Onchocerca volvulus Alpha-1b adrenergic receptor   515 aa 429 aa 20.3 %
Echinococcus granulosus biogenic amine 5HT receptor Alpha-1a adrenergic receptor   466 aa 418 aa 30.4 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Echinococcus granulosus peptidyl prolyl cis trans isomerase FKBP4 0.0141923 0.314834 1
Leishmania major peptidylprolyl isomerase-like protein 0.0141923 0.314834 1
Trypanosoma brucei FK506-binding protein (FKBP)-type peptidyl-prolyl isomerase, putative 0.0141923 0.314834 1
Trypanosoma cruzi peptidyl-prolyl cis-trans isomerase, putative 0.0141923 0.314834 1
Trichomonas vaginalis peptidylprolyl isomerase, putative 0.0141923 0.314834 1
Entamoeba histolytica peptidyl-prolyl cis-trans isomerase, FKBP-type , putative 0.0141923 0.314834 0.5
Giardia lamblia 70 kDa peptidylprolyl isomerase, putative 0.0141923 0.314834 1
Treponema pallidum peptidyl-prolyl cis-trans isomerase, FKBP-type, 22 kDa (fklB) 0.0141923 0.314834 1
Echinococcus multilocularis fk506 binding protein 0.0141923 0.314834 1
Echinococcus granulosus thioredoxin glutathione reductase 0.00761339 0.145811 0.430596
Plasmodium falciparum thioredoxin reductase 0.00761339 0.145811 0.430596
Trypanosoma cruzi FK506-binding protein (FKBP)-type peptidyl-prolyl isomerase, putative 0.0141923 0.314834 1
Plasmodium falciparum glutathione reductase 0.00761339 0.145811 0.430596
Trichomonas vaginalis peptidylprolyl isomerase, putative 0.0141923 0.314834 1
Brugia malayi dihydrolipoyl dehydrogenase, mitochondrial precursor, putative 0.00263827 0.0179914 0.0571455
Schistosoma mansoni immunophilin 0.0141923 0.314834 0.302281
Plasmodium vivax glutathione reductase, putative 0.00761339 0.145811 0.430596
Brugia malayi Thioredoxin reductase 0.00761339 0.145811 0.463135
Trypanosoma brucei trypanothione reductase 0.00761339 0.145811 0.430596
Echinococcus multilocularis peptidyl prolyl cis trans isomerase FKBP4 0.0129403 0.282667 0.891637
Leishmania major fk506-binding protein 1-like protein 0.0141923 0.314834 1
Trichomonas vaginalis fk506-binding protein, putative 0.0141923 0.314834 1
Mycobacterium tuberculosis NADPH-dependent mycothiol reductase Mtr 0.00761339 0.145811 1
Giardia lamblia FKBP-type peptidyl-prolyl cis-trans isomerase 0.0141923 0.314834 1
Leishmania major trypanothione reductase 0.00761339 0.145811 0.430596
Wolbachia endosymbiont of Brugia malayi dihydrolipoamide dehydrogenase E3 component 0.00263827 0.0179914 0.5
Plasmodium vivax 70 kDa peptidylprolyl isomerase, putative 0.0141923 0.314834 1
Loa Loa (eye worm) hypothetical protein 0.0129403 0.282667 0.80969
Loa Loa (eye worm) FKBP-type peptidyl-prolyl cis-trans isomerase-12 0.0141923 0.314834 1
Echinococcus multilocularis thioredoxin glutathione reductase 0.00761339 0.145811 0.430596
Trypanosoma cruzi peptidyl-prolyl cis-trans isomerase, putative 0.0141923 0.314834 1
Echinococcus granulosus peptidyl prolyl cis trans isomerase FKBP1A 0.0141923 0.314834 1
Loa Loa (eye worm) FKBP5 protein 0.0141923 0.314834 1
Trypanosoma cruzi trypanothione reductase, putative 0.00761339 0.145811 0.430596
Schistosoma mansoni amine GPCR 0.0408611 1 1
Schistosoma mansoni immunophilin FK506 binding protein FKBP12 0.0141923 0.314834 0.302281
Mycobacterium leprae DIHYDROLIPOAMIDE DEHYDROGENASE LPD (LIPOAMIDE REDUCTASE (NADH)) (LIPOYL DEHYDROGENASE) (DIHYDROLIPOYL DEHYDROGENASE) (DIAPHORASE 0.00263827 0.0179914 0.5
Brugia malayi FKBP-type peptidyl-prolyl cis-trans isomerase-59, BmFKBP59 0.0141923 0.314834 1
Toxoplasma gondii thioredoxin reductase 0.00761339 0.145811 1
Trypanosoma cruzi FK506-binding protein (FKBP)-type peptidyl-prolyl isomerase, putative 0.0141923 0.314834 1
Chlamydia trachomatis dihydrolipoyl dehydrogenase 0.00263827 0.0179914 0.5
Trichomonas vaginalis immunophilin, putative 0.0141923 0.314834 1
Mycobacterium ulcerans FK-506 binding protein, peptidyl-prolyl cis-trans isomerase 0.0141923 0.314834 1
Plasmodium falciparum peptidyl-prolyl cis-trans isomerase FKBP35 0.0141923 0.314834 1
Entamoeba histolytica peptidyl-prolyl cis-trans isomerase, FKBP-type, putative 0.0141923 0.314834 0.5
Brugia malayi FKBP-type peptidyl-prolyl cis-trans isomerase-12, BmFKBP-12 0.0141923 0.314834 1
Echinococcus multilocularis peptidyl prolyl cis trans isomerase FKBP4 0.0141923 0.314834 1
Brugia malayi glutathione reductase 0.00761339 0.145811 0.463135
Schistosoma mansoni immunophilin 0.0141923 0.314834 0.302281
Trypanosoma brucei peptidyl-prolyl cis-trans isomerase, putative 0.0141923 0.314834 1
Plasmodium vivax thioredoxin reductase, putative 0.00761339 0.145811 0.430596
Wolbachia endosymbiont of Brugia malayi dihydrolipoamide dehydrogenase E3 component 0.00263827 0.0179914 0.5
Schistosoma mansoni immunophilin 0.0129403 0.282667 0.269525
Echinococcus granulosus peptidyl prolyl cis trans isomerase FKBP4 0.0129403 0.282667 0.891637

Activities

Activity type Activity value Assay description Source Reference
IC50 (functional) = 0.12 uM Antitrypanosomal activity against Trypanosoma brucei rhodesiense bloodstream trypomastigotes ChEMBL. 19414258
IC50 (functional) = 0.53 uM Antibacterial activity against intraerythrocytic form of Plasmodium falciparum ChEMBL. 19414258
IC50 (functional) = 1.78 uM Antileishmanial activity against Leishmania donovani axenic amastigotes ChEMBL. 19414258
IC50 (functional) = 2.63 uM Antioxidant activity against formation of ROS was determined in t-BuOOH treated LNCaP cells after 24 h of incubation with compounds (1-100 uM) ChEMBL. 15633998
IC50 (functional) = 2.63 uM Antioxidant activity against formation of ROS was determined in t-BuOOH treated LNCaP cells after 24 h of incubation with compounds (1-100 uM) ChEMBL. 15633998
IC50 (functional) = 3.68 uM Antitrypanosomal activity against Trypanosoma cruzi amastigotes infected in rat L6 cells ChEMBL. 19414258
IC50 (functional) = 8.82 uM Antiproliferative activity was determined by colorimetric MTS assay in LNCaP cells after 72 h of incubation with compounds (1-100 uM) ChEMBL. 15633998
IC50 (functional) = 8.82 uM Antiproliferative activity was determined by colorimetric MTS assay in LNCaP cells after 72 h of incubation with compounds (1-100 uM) ChEMBL. 15633998
Inhibition (binding) Inhibition of human glutathione reductase at 10 uM by spectrophotometry in presence of 100 uM GSSG ChEMBL. 19414258
Inhibition (binding) = 53 % Inhibition of Trypanosoma cruzi recombinant trypanothione reductase at 25 uM by spectrophotometry using 50 uM trypanothione disulfide ChEMBL. 19414258
Inhibition (binding) = 57 % Inhibition of Trypanosoma cruzi recombinant trypanothione reductase at 25 uM by spectrophotometry using 100 uM trypanothione disulfide ChEMBL. 19414258
Kd (functional) = 7.64 Blocking activity was assessed by antagonism of (-)-noradrenaline induced contraction of rat prostatic vas deferens (alpha1A adrenoreceptor) ChEMBL. 15633998
Kd (functional) = 8.51 Blocking activity was assessed by antagonism of (-)-phenylephrine induced contraction of rat spleen (alpha1B adrenoreceptor) ChEMBL. 15633998
Kd (functional) = 9.05 Blocking activity was assessed by antagonism of (-)-noradrenaline induced contraction of rat thoracic aorta (alpha1D adrenoreceptor) ChEMBL. 15633998
Ki (binding) = -9.17 Equilibrium dissociation constant was evaluated by radio-receptor binding assays using [3H]-prazosin to label cloned human alpha 1b expressed in CHO cells ChEMBL. 15633998
Ki (binding) = -9.03 Equilibrium dissociation constant was evaluated by radio-receptor binding assays using [3H]-prazosin to label cloned human alpha 1d expressed in CHO cells ChEMBL. 15633998
Ki (binding) = -8.9 Equilibrium dissociation constant was evaluated by radio-receptor binding assays using [3H]-prazosin to label cloned human alpha 1a expressed in CHO cells ChEMBL. 15633998
Ki (binding) = 7.5 uM Inhibition of Trypanosoma cruzi recombinant trypanothione reductase by spectrophotometry ChEMBL. 19414258
Ki (binding) = 22 uM Inhibition of Trypanosoma cruzi recombinant trypanothione reductase by spectrophotometry-based mixed inhibition type assay ChEMBL. 19414258
Log Ki (binding) = 8.9 Equilibrium dissociation constant was evaluated by radio-receptor binding assays using [3H]-prazosin to label cloned human alpha 1a expressed in CHO cells ChEMBL. 15633998
Log Ki (binding) = 9.03 Equilibrium dissociation constant was evaluated by radio-receptor binding assays using [3H]-prazosin to label cloned human alpha 1d expressed in CHO cells ChEMBL. 15633998
Log Ki (binding) = 9.17 Equilibrium dissociation constant was evaluated by radio-receptor binding assays using [3H]-prazosin to label cloned human alpha 1b expressed in CHO cells ChEMBL. 15633998
pA2 (functional) = 7.64 Blocking activity was assessed by antagonism of (-)-noradrenaline induced contraction of rat prostatic vas deferens (alpha1A adrenoreceptor) ChEMBL. 15633998
pA2 (functional) = 8.51 Blocking activity was assessed by antagonism of (-)-phenylephrine induced contraction of rat spleen (alpha1B adrenoreceptor) ChEMBL. 15633998
pA2 (functional) = 9.05 Blocking activity was assessed by antagonism of (-)-noradrenaline induced contraction of rat thoracic aorta (alpha1D adrenoreceptor) ChEMBL. 15633998

Phenotypes

Whole-cell/tissue/organism interactions

Species name Source Reference Is orphan
Trypanosoma brucei gambiense 19414258
Trypanosoma cruzi ChEMBL23 19414258
Leishmania donovani ChEMBL23 19414258
Plasmodium falciparum ChEMBL23 19414258
Homo sapiens ChEMBL23 15633998

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.

External resources for this compound

Bibliographic References

2 literature references were collected for this gene.

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