5,7-Dichloro-4-oxo-1,4-dihydro-quinoline-2-carboxylic acid

ID: ALA50267

Chembl Id: CHEMBL50267

Cas Number: 131123-76-7

PubChem CID: 1779

Product Number: T58484

Max Phase: Preclinical

Molecular Formula: C10H5Cl2NO3

Molecular Weight: 258.06

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Synonyms: 5,7-Dichlorokynurenic Acid | 5,7-Dichlorokynurenic acid|131123-76-7|5,7-DICHLORO-4-HYDROXYQUINOLINE-2-CARBOXYLIC ACID|5,7-Dcka|5,7-Dichloroquinurenic acid|5,7-Dichorokynurenic acid|2-Quinolinecarboxylic acid, 5,7-dichloro-4-hydroxy-|5,7-Dichloro-4-hydroxy-2-quinolinecarboxylic acid|5,7-dichloro-4-oxo-1H-quinoline-2-carboxylic acid|T61ORK73PY|CHEMBL50267|1pbq|SR-01000075445|UNII-T61ORK73PY|2-Quinolinecarboxylicacid, 5,7-dichloro-4-hydroxy-|Spectrum_001455|Tocris-0286|SpecPlus_000760|Lopac-D-138|SShow More

Canonical SMILES:  O=C(O)c1cc(O)c2c(Cl)cc(Cl)cc2n1

Standard InChI:  InChI=1S/C10H5Cl2NO3/c11-4-1-5(12)9-6(2-4)13-7(10(15)16)3-8(9)14/h1-3H,(H,13,14)(H,15,16)

Standard InChI Key:  BGKFPRIGXAVYNX-UHFFFAOYSA-N

Alternative Forms

  1. Alternative Forms:

Associated Targets(Human)

GRIN1 Tclin Glutamate [NMDA] receptor (933 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GRIA4 Tclin Glutamate receptor ionotropic AMPA (265 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GRIK1 Tclin Glutamate receptor ionotropic kainate (68 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ALB Tchem Serum albumin (2651 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
NGFR Tclin Low affinity neurotrophin receptor p75NTR (32 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MEN1 Tchem Menin/Histone-lysine N-methyltransferase MLL (48157 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TSHR Tclin Thyroid stimulating hormone receptor (29986 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TDP1 Tchem Tyrosyl-DNA phosphodiesterase 1 (345557 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C19 Tchem Cytochrome P450 2C19 (29246 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ALOX15 Tchem Arachidonate 15-lipoxygenase (7108 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BLM Tchem Bloom syndrome protein (4248 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HPGD Tchem 15-hydroxyprostaglandin dehydrogenase [NAD+] (24926 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EHMT2 Tchem Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 (93046 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP1A2 Tchem Cytochrome P450 1A2 (26471 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HEK293 (82097 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ARSA Tbio Cerebroside-sulfatase (655 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC6 Tclin Histone deacetylase 6 (20808 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Gria2 Glutamate receptor ionotropic, AMPA (2103 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Grin1 Glutamate (NMDA) receptor subunit zeta 1 (2166 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Grik1 Glutamate receptor ionotropic, kainate (722 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Grin1 Glutamate NMDA receptor (6467 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Grin1 Glutamate receptors; NMDA/AMPA (104 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Gria2 Glutamate receptor ionotropic, AMPA (167 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ffp 4'-phosphopantetheinyl transferase ffp (24982 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Impa1 Inositol monophosphatase 1 (16203 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Chrm1 Muscarinic acetylcholine receptor M1 (3437 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Txnrd1 Thioredoxin reductase 1, cytoplasmic (45279 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SARS-CoV-2 (38078 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
rep Replicase polyprotein 1ab (11336 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: YesOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 258.06Molecular Weight (Monoisotopic): 256.9646AlogP: 2.95#Rotatable Bonds: 1
Polar Surface Area: 70.42Molecular Species: ACIDHBA: 3HBD: 2
#RO5 Violations: HBA (Lipinski): 4HBD (Lipinski): 2#RO5 Violations (Lipinski):
CX Acidic pKa: 3.69CX Basic pKa: 0.38CX LogP: 3.08CX LogD: -0.29
Aromatic Rings: 2Heavy Atoms: 16QED Weighted: 0.82Np Likeness Score: -0.53

References

1. Leeson PD, Baker R, Carling RW, Curtis NR, Moore KW, Williams BJ, Foster AC, Donald AE, Kemp JA, Marshall GR..  (1991)  Kynurenic acid derivatives. Structure-activity relationships for excitatory amino acid antagonism and identification of potent and selective antagonists at the glycine site on the N-methyl-D-aspartate receptor.,  34  (4): [PMID:1826744] [10.1021/jm00108a002]
2. Salituro FG, Harrison BL, Baron BM, Nyce PL, Stewart KT, Kehne JH, White HS, McDonald IA..  (1992)  3-(2-Carboxyindol-3-yl)propionic acid-based antagonists of the N-methyl-D-aspartic acid receptor associated glycine binding site.,  35  (10): [PMID:1534125] [10.1021/jm00088a014]
3. Carling RW, Leeson PD, Moseley AM, Baker R, Foster AC, Grimwood S, Kemp JA, Marshall GR..  (1992)  2-Carboxytetrahydroquinolines. Conformational and stereochemical requirements for antagonism of the glycine site on the NMDA receptor.,  35  (11): [PMID:1534583] [10.1021/jm00089a003]
4. Colotta V, Catarzi D, Varano F, Calabri FR, Filacchioni G, Costagli C, Galli A..  (2004)  3-hydroxy-quinazoline-2,4-dione as a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists.,  14  (9): [PMID:15081038] [10.1016/j.bmcl.2004.01.109]
5. Catarzi D, Colotta V, Varano F, Cecchi L, Filacchioni G, Galli A, Costagli C..  (1999)  4,5-Dihydro-1,2,4-triazolo[1,5-a]quinoxalin-4-ones: excitatory amino acid antagonists with combined glycine/NMDA and AMPA receptor affinity.,  42  (13): [PMID:10395489] [10.1021/jm981102r]
6. Catarzi D, Colotta V, Varano F, Calabri FR, Filacchioni G, Galli A, Costagli C, Carlà V..  (2004)  Synthesis and biological evaluation of analogues of 7-chloro-4,5-dihydro-4- oxo-8-(1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylic acid (TQX-173) as novel selective AMPA receptor antagonists.,  47  (1): [PMID:14695840] [10.1021/jm030906q]
7. Jimonet P, Audiau F, Aloup J, Barreau M, Blanchard J, Bohme A, Boireau A, Cheve M, Damour D, Doble A, Lavayre J, Dutruc-Rosset G, Randle JC, Rataud J, Stutzmann J, Mignani S.  (1994)  Synthesis and sar of 2h-1,2,4-benzothiadiazine-1,1-dioxide-3- carboxylic acid derivatives as novel potent glycine antagonists of the nmda receptor-channel complex,  (23): [10.1016/S0960-894X(01)80586-2]
8. Epperson JR, Hewawasam P, Meanwell NA, Boissard CG, Gribkoff VK, Post-Munson D.  (1993)  Synthesis and excitatory amino acid pharmacology of some novel quinoxalinediones,  (12): [10.1016/S0960-894X(01)80768-X]
9. Salituro FG, Harrison BL, Baron BM, Nyce PL, Stewart KT, McDonald IA..  (1990)  3-(2-carboxyindol-3-yl)propionic acid derivatives: antagonists of the strychnine-insensitive glycine receptor associated with the N-methyl-D-aspartate receptor complex.,  33  (11): [PMID:2146391] [10.1021/jm00173a003]
10. Leeson PD, Baker R, Carling RW, Kulagowski JJ, Mawer IM, Ridgill MP, Rowley M, Smith JD, Stansfield I, Stevenson GI, Foster AC, Kemp JA.  (1993)  Amino acid bioisosteres: design of 2-quinolone derivatives as glycine-site N-methyl-D-aspartate receptor antagonists,  (2): [10.1016/S0960-894X(01)80897-0]
11. Conti P, De Amici M, Joppolo Di Ventimiglia S, Stensbøl TB, Madsen U, Bräuner-Osborne H, Russo E, De Sarro G, Bruno G, De Micheli C..  (2003)  Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.,  46  (14): [PMID:12825948] [10.1021/jm0308085]
12. Harrison BL, Baron BM, Cousino DM, McDonald IA..  (1990)  4-[(Carboxymethyl)oxy]- and 4-[(carboxymethyl)amino]-5,7-dichloroquinoline-2-carboxylic acid: new antagonists of the strychnine-insensitive glycine binding site on the N-methyl-D-aspartate receptor complex.,  33  (12): [PMID:2147957] [10.1021/jm00174a005]
13. Catarzi D, Colotta V, Varano F, Filacchioni G, Galli A, Costagli C, Carlà V..  (2001)  Synthesis, ionotropic glutamate receptor binding affinity, and structure-activity relationships of a new set of 4,5-dihydro-8-heteroaryl-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates analogues of TQX-173.,  44  (19): [PMID:11543685] [10.1021/jm010862q]
14. McQuaid LA, Smith EC, South KK, Mitch CH, Schoepp DD, True RA, Calligaro DO, O'Malley PJ, Lodge D, Ornstein PL..  (1992)  Synthesis and excitatory amino acid pharmacology of a series of heterocyclic-fused quinoxalinones and quinazolinones.,  35  (18): [PMID:1382133] [10.1021/jm00096a002]
15. McQuaid LA, Smith EC, Lodge D, Pralong E, Wikel JH, Calligaro DO, O'Malley PJ..  (1992)  3-Phenyl-4-hydroxyquinolin-2(1H)-ones: potent and selective antagonists at the strychnine-insensitive glycine site on the N-methyl-D-aspartate receptor complex.,  35  (18): [PMID:1326635] [10.1021/jm00096a019]
16. Catarzi D, Colotta V, Varano F, Cecchi L, Filacchioni G, Galli A, Costagli C, Carlà V..  (2000)  7-Chloro-4,5-dihydro-8-(1,2,4-triazol-4-yl)-4-oxo-1,2,4-triazolo[1, 5-a]quinoxaline-2- carboxylates as novel highly selective AMPA receptor antagonists.,  43  (21): [PMID:11052786] [10.1021/jm0009686]
17. Nagata R, Tanno N, Kodo T, Ae N, Yamaguchi H, Nishimura T, Antoku F, Tatsuno T, Kato T, Tanaka Y..  (1994)  Tricyclic quinoxalinediones: 5,6-dihydro-1H-pyrrolo[1,2,3-de] quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de] quinoxaline-2,3-diones as potent antagonists for the glycine binding site of the NMDA receptor.,  37  (23): [PMID:7966156] [10.1021/jm00049a015]
18. Leeson PD, Iversen LL..  (1994)  The glycine site on the NMDA receptor: structure-activity relationships and therapeutic potential.,  37  (24): [PMID:7990104] [10.1021/jm00050a001]
19. Rowley M, Kulagowski JJ, Watt AP, Rathbone D, Stevenson GI, Carling RW, Baker R, Marshall GR, Kemp JA, Foster AC, Grimwood S, Hargreaves R, Hurley C, Saywell KL, Tricklebank MD, Leeson PD..  (1997)  Effect of plasma protein binding on in vivo activity and brain penetration of glycine/NMDA receptor antagonists.,  40  (25): [PMID:9406596] [10.1021/jm970417o]
20. Jaen JC, Laborde E, Bucsh RA, Caprathe BW, Sorenson RJ, Fergus J, Spiegel K, Marks J, Dickerson MR, Davis RE..  (1995)  Kynurenic acid derivatives inhibit the binding of nerve growth factor (NGF) to the low-affinity p75 NGF receptor.,  38  (22): [PMID:7473570] [10.1021/jm00022a008]
21. Grasso S, Micale N, Zappalà M, Galli A, Costagli C, Menniti FS, De Micheli C..  (2003)  Characterization of the mechanism of anticonvulsant activity for a selected set of putative AMPA receptor antagonists.,  13  (3): [PMID:12565947] [10.1016/s0960-894x(02)00955-1]
22. Salituro FG, Tomlinson RC, Baron BM, Demeter DA, Weintraub HJ, McDonald IA.  (1991)  Design, synthesis and molecular modeling of 3-acylamino-2- Carboxyindole NMDA receptor glycine-site antagonists,  (9): [10.1016/S0960-894X(01)81105-7]
23. Moore KW, Leeson PD, Carling RW, Ticklebank MD, Singh L.  (1993)  Anticonvulsant activity of glycine-site NMDA antagonists. 1. 2-carboxyl prodrugs of 5,7-dichlorokynurenic acid,  (1): [10.1016/S0960-894X(00)80092-X]
24. Carling RW, Leeson PD, Moseley AM, Smith JD, Saywell K, Tricklebank MD, Kemp JA, Marshall GR, Foster AC, Grimwood S.  (1993)  Anticonvulsant activity of glycine-site NMDA antagonists. 2. trans 2-carboxy-4-substituted tetrahydroquinolines.,  (1): [10.1016/S0960-894X(00)80093-1]
25. Hays SJ, Boxer PA, Taylor CP, Vartanian MG, Robichaud LJ, Nielsen E.  (1993)  N-sulfonyl derivatives of 6,7-dichloro 3,4-dihydro-3-oxo-quinoxalinecarboxylate as glycine-site NMDA and AMPA antagonists,  (1): [10.1016/S0960-894X(00)80095-5]
26. Smith EC, McQuaid LA, Calligaro DO, O'Malley PJ.  (1993)  Structure-activity relationships of a series of glycine antagonists related to 5,7-dichlorokynurenic acid and 3-(2-carboxy-6-chloroindol-3-yl)acetic acid,  (1): [10.1016/S0960-894X(00)80096-7]
27. Urwyler S, Floersheim P, Roy BL, Koller M..  (2009)  Drug design, in vitro pharmacology, and structure-activity relationships of 3-acylamino-2-aminopropionic acid derivatives, a novel class of partial agonists at the glycine site on the N-methyl-D-aspartate (NMDA) receptor complex.,  52  (16): [PMID:19642674] [10.1021/jm900363q]
28. Diamandis P, Wildenhain J, Clarke ID, Sacher AG, Graham J, Bellows DS, Ling EK, Ward RJ, Jamieson LG, Tyers M, Dirks PB..  (2007)  Chemical genetics reveals a complex functional ground state of neural stem cells.,  (5): [PMID:17417631] [10.1038/nchembio873]
29. PubChem BioAssay data set, 
30. PubChem BioAssay data set, 
31. PubChem BioAssay data set, 
32. PubChem BioAssay data set, 
33. PubChem BioAssay data set, 
34. PubChem BioAssay data set, 
35. Colotta V, Lenzi O, Catarzi D, Varano F, Squarcialupi L, Costagli C, Galli A, Ghelardini C, Pugliese AM, Maraula G, Coppi E, Pellegrini-Giampietro DE, Pedata F, Sabbadin D, Moro S..  (2012)  3-Hydroxy-1H-quinazoline-2,4-dione derivatives as new antagonists at ionotropic glutamate receptors: molecular modeling and pharmacological studies.,  54  [PMID:22704999] [10.1016/j.ejmech.2012.05.036]
36. PubChem BioAssay data set, 
37. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]
38. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]
39. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]
40. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]