Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
 

 

TTD Target ID: TTDC00291

Target Information
NameD(4) dopamine receptor    
Type of targetClinical trial target    
SynonymsD(2C)D(4) dopamine receptor dopamine receptor    
Dopamine D4 receptor    
DiseaseParkinson's disease    [1]
Psychiatric illness    [2]
Respiratory diseases    [3]
Drug(s)NGD 94-1Phase ISchizophrenia[4]
BelaperidoneDiscontinuedSchizophrenia[4]
SarizotanDiscontinued in Phase IIParkinsoní»s Disease[5]
SonepiprazoleDiscontinuedSchizophrenia[4]
HMR-2934No development reportedSchizophrenia[4]
PD-165167PreclinicalSchizophrenia[4]
SPI-376PreclinicalSchizophrenia[4]
U-99363EPreclinicalSchizophrenia[4]
BioChemical ClassG-protein coupled receptor (rhodopsin family)    
PathwayNeuroactive ligand-receptor interaction
UniProt IDP21917
FunctionThis is one of the five types (D1 to D5) of receptors for dopamine, and the activity of this receptor is mediated by g proteins which activate adenylyl cyclase.    
SequenceMGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVA TERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCT ASIFNLCAISVDRFVAVAVPLRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGR DPAVCRLEDRDYVVYSSVCSFFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSG PGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPGLPPDPCGPDCAPPAPG LPQDPCGPDCAPPAPGLPRGPCGPDCAPPAPGLPQDPCGPDCAPPAPGLPPDPCGSNCAP PDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWTPFFVVHITQALC PACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC
Related US Patent6,479,491
Target ValidationClick to Find Target Validation Information.    
Inhibitor (+/-)-nantenine[6]
(-)3-[7]
(4-Ethynyl-cyclohex-3-enyl)-dipropyl-amine[8]
(4-Phenylethynyl-cyclohex-3-enyl)-dipropyl-amine[8]
1- (4-[9]
1-Benzyl-4- (2-ethynyl-pyrrol-1-yl)-piperidine[10]
1-Benzyl-4- (2-iodo-pyrrol-1-yl)-piperidine[10]
1-Benzyl-4- (2-oxazol-5-yl-pyrrol-1-yl)-piperidine[10]
1-Benzyl-4- (3-oxazol-5-yl-pyrrol-1-yl)-piperidine[10]
1-Benzyl-4-pyrrol-1-yl-piperidine[10]
1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine[11]
1-[2- (2-Benzyl-phenoxy)-ethyl]-piperidine[12]
1-[2- (2-Benzyl-phenoxy)-ethyl]-pyrrolidine[12]
1-[3- (2-Benzyl-phenoxy)-propyl]-pyrrolidine[12]
3- (1-Propyl-piperidin-3-yl)-phenol[13]
3- (2-Benzylamino-ethoxy)-phenol[14]
3- (4-Methyl-piperidin-1-ylmethyl)-1H-indole[15]
3- (4-Phenyl-piperazin-1-ylmethyl)-1H-indole[15]
3- (4-Phenyl-piperidin-1-ylmethyl)-1H-indole[15]
4- (2-Benzylamino-ethoxy)-1,3-dihydro-indol-2-one[14]
4- (4-Benzyl-piperazin-1-yl)-1H-benzoimidazole[16]
4- (4-Benzyl-piperazin-1-yl)-1H-indole[16]
4- (4-Benzyl-piperazin-1-yl)-5-chloro-1H-indole[16]
4- (4-Benzyl-piperazin-1-yl)-7-bromo-1H-indole[16]
4-[2- (2-Benzyl-phenoxy)-ethyl]-morpholine[12]
A-425444[17]
A-80426[18]
ABT-670[17]
BP-897[19]
Benzyl-[2- (1H-indazol-4-yloxy)-ethyl]-amine[14]
Benzyl-[2- (1H-indol-4-yloxy)-ethyl]-amine[14]
DIHYDREXIDINE[20]
FLUMEZAPINE[21]
FLUTROLINE[22]
ISOCLOZAPINE[11]
ISOLOXAPINE[23]
JL-18,   NCGC00094013-01[24]
L-741626[25]
L-741742[26]
L-745870[27]
N- (4-Dipropylaminobutyl)-4-biphenylcarboxamide[28]
N- (4-Propylaminobutyl)-4-biphenylcarboxamide[28]
PG-01037[29]
Phenyltoloxamine[12]
QUINPIROLE[30]
SB-271046[31]
SPIPERONE[32]
STEPHOLIDINE[20]
UH-232[33]
[2- (1H-Benzoimidazol-4-yloxy)-ethyl]-benzyl-amine[14]
AgonistSarizotan[5]
AntagonistA-381393[34][35]
Belaperidone[4]
FAUC 113[35]
HMR-2934[4]
L-745,870[34][35]
NGD 94-1[4]
PD-165167[4]
BinderSPI-376[4]
Sonepiprazole[4]
U-99363E[4]
MultitargetHMR-2934[4]
Sarizotan[5]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Tolerance to some behavioural effects of lisuride, a dopamine receptor agonist, and reverse tolerance to others, after repeated administration. Neuropharmacology. 1985 Mar;24(3):199-206. To Reference
Ref 2Dopamine D4 receptors and development of newer antipsychotic drugs. Fundam Clin Pharmacol. 2000 Nov-Dec;14(6):529-39. To Reference
Ref 3Effect of dopamine receptor agonists on sensory nerve activity: possible therapeutic targets for the treatment of asthma and COPD. Br J Pharmacol. 2002 Jun;136(4):620-8. To Reference
Ref 4The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31. To Reference
Ref 5Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42. To Reference
Ref 6Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. To Reference
Ref 7J Med Chem. 1993 Oct 15;36(21):3188-96.Substituted 3-phenylpiperidines: new centrally acting dopamine autoreceptor antagonists. To Reference
Ref 8J Med Chem. 2000 Feb 24;43(4):756-62.Conjugated enynes as nonaromatic catechol bioisosteres: synthesis, binding experiments, and computational studies of novel dopamine receptor agonists recognizing preferentially the D(3) subtype. To Reference
Ref 9Bioorg Med Chem Lett. 2006 Jun 1;16(11):2955-9. Epub 2006 Mar 24.Synthesis and biological investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype. To Reference
Ref 10Bioorg Med Chem Lett. 1999 Nov 1;9(21):3143-6.Piperidinylpyrroles: design, synthesis and binding properties of novel and selective dopamine D4 receptor ligands. To Reference
Ref 11J Med Chem. 1982 Jul;25(7):855-8.Affinity of 10-(4-methylpiperazino)dibenz[b,f]oxepins for clozapine and spiroperidol binding sites in rat brain. To Reference
Ref 12J Med Chem. 2004 Aug 12;47(17):4155-8.Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 receptor selectivity. To Reference
Ref 13J Med Chem. 1988 Aug;31(8):1621-5.Dopamine autoreceptor agonists as potential antipsychotics. 1. (Aminoalkoxy)anilines. To Reference
Ref 14Bioorg Med Chem Lett. 1999 Sep 6;9(17):2593-8.New generation dopaminergic agents. 7. Heterocyclic bioisosteres that exploit the 3-OH-phenoxyethylamine D2 template. To Reference
Ref 15J Med Chem. 1996 May 10;39(10):1941-2.3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor. To Reference
Ref 16Bioorg Med Chem Lett. 1998 Oct 6;8(19):2675-80.New generation dopaminergic agents. 5. Heterocyclic bioisosteres that exploit the 3-OH-N1-phenylpiperazine dopaminergic template. To Reference
Ref 17J Med Chem. 2006 Dec 14;49(25):7450-65.Discovery of 3-methyl-N-(1-oxy-3',4',5',6'-tetrahydro-2'H-[2,4'-bipyridine]-1'-ylmethyl)benzamide (ABT-670), an orally bioavailable dopamine D4 agonist for the treatment of erectile dysfunction. To Reference
Ref 18J Med Chem. 2005 Mar 24;48(6):2054-71.Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking activity. To Reference
Ref 19J Med Chem. 2005 May 5;48(9):3171-81.Enantiomerically pure hexahydropyrazinoquinolines as potent and selective dopamine 3 subtype receptor ligands. To Reference
Ref 20Bioorg Med Chem. 2009 Oct 1;17(19):6898-907. Epub 2009 Aug 20.Dibenzazecine scaffold rebuilding--is the flexibility always essential for high dopamine receptor affinities? To Reference
Ref 21J Med Chem. 1982 Oct;25(10):1133-40.Effects of conformationally restricted 4-piperazinyl-10H-thienobenzodiazepine neuroleptics on central dopaminergic and cholinergic systems. To Reference
Ref 22J Med Chem. 1980 Jun;23(6):635-43.Neuroleptic activity in 5-aryltetrahydro-gamma-carbolines. To Reference
Ref 23J Med Chem. 1981 Sep;24(9):1021-6.Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. To Reference
Ref 24J Med Chem. 1996 Jun 21;39(13):2435-7.(S)-(-)-4-[4-[2-(isochroman-1-yl)ethyl]-piperazin-1-yl] benzenesulfonamide, a selective dopamine D4 antagonist. To Reference
Ref 25Bioorg. Med. Chem. 18(14):5291-5300 (2010) To Reference
Ref 26J Med Chem. 1996 May 10;39(10):1943-5.5-(4-Chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)isoxazole: a potent, selective antagonist at human cloned dopamine D4 receptors. To Reference
Ref 27Bioorg Med Chem. 2009 Feb 15;17(4):1716-23. Epub 2008 Dec 31.Synthesis and evaluation of ligands for D2-like receptors: the role of common pharmacophoric groups. To Reference
Ref 28J Med Chem. 2008 Nov 13;51(21):6829-38. Epub 2008 Oct 4.Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies. To Reference
Ref 29J Med Chem. 2007 Aug 23;50(17):4135-46. Epub 2007 Aug 2.Heterocyclic analogues of N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)arylcarboxamides with functionalized linking chains as novel dopamine D3 receptor ligands: potential substance abuse therapeutic agents. To Reference
Ref 30J Med Chem. 2005 Sep 8;48(18):5771-9.Pharmacophore-guided drug discovery investigations leading to bioactive 5-aminotetrahydropyrazolopyridines. Implications for the binding mode of heterocyclic dopamine D3 receptor agonists. To Reference
Ref 31Bioorg Med Chem Lett. 2008 Jan 15;18(2):738-43. Epub 2007 Nov 17.Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists. To Reference
Ref 32J Med Chem. 2005 Feb 10;48(3):694-709.Modeling the similarity and divergence of dopamine D2-like receptors and identification of validated ligand-receptor complexes. To Reference
Ref 33Bioorg. Med. Chem. Lett. 7(21):2759-2764 (1997) To Reference
Ref 34Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI. Psychopharmacology (Berl). 2009 Apr;203(2):265-77. Epub 2008 Jul 6. To Reference
Ref 35Comparative molecular field analysis of dopamine D4 receptor antagonists including 3-[4-(4-chlorophenyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 113), 3-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-1H-pyrrolo-[2,3-b]pyridine (L-745,870), and clozapine. J Med Chem. 2001 Apr 12;44(8):1151-7. To Reference



 

Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.


Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore


All rights reserved.

 
   
           
 
Computer-aided Drug Design
About BIDD | Databases | Software | Teaching | Research |  Links

Department of Computational Science | National University of Singapore | Blk S17, 3 Science Drive 2, Singapore 117543