Target Information
| Target General Information | Top | |||||
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| Target ID |
T24983
(Former ID: TTDC00291)
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| Target Name |
Dopamine D4 receptor (D4R)
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| Synonyms |
DRD4; D(2C)D(4) dopamine receptor dopamine receptor
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| Gene Name |
DRD4
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Allergic/hypersensitivity disorder [ICD-11: 4A80-4A8Z] | |||||
| 2 | Schizophrenia [ICD-11: 6A20] | |||||
| Function |
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVA
TERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCT ASIFNLCAISVDRFVAVAVPLRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGR DPAVCRLEDRDYVVYSSVCSFFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSG PGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPSLPQDPCGPDCAPPAPG LPPDPCGSNCAPPDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWT PFFVVHITQALCPACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A04234 | |||||
| HIT2.0 ID | T49IR9 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Clozapine | Drug Info | Approved | Schizophrenia | [2], [3] | |
| 2 | Phenyltoloxamine | Drug Info | Approved | Allergy | [4] | |
| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | CM-2395 | Drug Info | Phase 3 | Schizophrenia | [5] | |
| 2 | L-745,870 | Drug Info | Phase 2 | Psychotic disorder | [6] | |
| 3 | RP5063 | Drug Info | Phase 2 | Schizophrenia | [7] | |
| 4 | NGD 94-1 | Drug Info | Phase 1 | Schizophrenia | [3], [8] | |
| Discontinued Drug(s) | [+] 7 Discontinued Drugs | + | ||||
| 1 | ABT-724 | Drug Info | Discontinued in Phase 2 | Erectile dysfunction | [9] | |
| 2 | Lu-35138 | Drug Info | Discontinued in Phase 2 | Psychotic disorder | [10] | |
| 3 | NGD-94-4 | Drug Info | Discontinued in Phase 1 | Schizophrenia | [11] | |
| 4 | Belaperidone | Drug Info | Terminated | Schizophrenia | [3] | |
| 5 | BIMG80 | Drug Info | Terminated | Psychotic disorder | [12] | |
| 6 | Sonepiprazole | Drug Info | Terminated | Schizophrenia | [3], [13] | |
| 7 | YM-43611 | Drug Info | Terminated | Psychotic disorder | [14] | |
| Preclinical Drug(s) | [+] 3 Preclinical Drugs | + | ||||
| 1 | PD-165167 | Drug Info | Preclinical | Schizophrenia | [3] | |
| 2 | SPI-376 | Drug Info | Preclinical | Schizophrenia | [3] | |
| 3 | U-99363E | Drug Info | Preclinical | Schizophrenia | [3] | |
| Mode of Action | [+] 6 Modes of Action | + | ||||
| Modulator | [+] 6 Modulator drugs | + | ||||
| 1 | Clozapine | Drug Info | [15] | |||
| 2 | NGD-94-4 | Drug Info | [23] | |||
| 3 | BIMG80 | Drug Info | [25] | |||
| 4 | YM-43611 | Drug Info | [26] | |||
| 5 | E-1455 | Drug Info | [38] | |||
| 6 | TKP-1002 | Drug Info | [38] | |||
| Inhibitor | [+] 44 Inhibitor drugs | + | ||||
| 1 | Phenyltoloxamine | Drug Info | [1] | |||
| 2 | A-80426 | Drug Info | [24] | |||
| 3 | (+/-)-nantenine | Drug Info | [27] | |||
| 4 | (4-Ethynyl-cyclohex-3-enyl)-dipropyl-amine | Drug Info | [28] | |||
| 5 | (4-Phenylethynyl-cyclohex-3-enyl)-dipropyl-amine | Drug Info | [28] | |||
| 6 | 1-(4-(1H-pyrazol-1-yl)benzyl)-4-phenylpiperazine | Drug Info | [29] | |||
| 7 | 1-Benzyl-4-(2-ethynyl-pyrrol-1-yl)-piperidine | Drug Info | [30] | |||
| 8 | 1-Benzyl-4-(2-iodo-pyrrol-1-yl)-piperidine | Drug Info | [30] | |||
| 9 | 1-Benzyl-4-(2-oxazol-5-yl-pyrrol-1-yl)-piperidine | Drug Info | [30] | |||
| 10 | 1-Benzyl-4-(3-oxazol-5-yl-pyrrol-1-yl)-piperidine | Drug Info | [30] | |||
| 11 | 1-Benzyl-4-pyrrol-1-yl-piperidine | Drug Info | [30] | |||
| 12 | 1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine | Drug Info | [31] | |||
| 13 | 1-[2-(2-Benzyl-phenoxy)-ethyl]-piperidine | Drug Info | [1] | |||
| 14 | 1-[2-(2-Benzyl-phenoxy)-ethyl]-pyrrolidine | Drug Info | [1] | |||
| 15 | 1-[3-(2-Benzyl-phenoxy)-propyl]-pyrrolidine | Drug Info | [1] | |||
| 16 | 3-(2-Benzylamino-ethoxy)-phenol | Drug Info | [32] | |||
| 17 | 3-(4-Methyl-piperidin-1-ylmethyl)-1H-indole | Drug Info | [33] | |||
| 18 | 3-(4-Phenyl-piperazin-1-ylmethyl)-1H-indole | Drug Info | [33] | |||
| 19 | 3-(4-Phenyl-piperidin-1-ylmethyl)-1H-indole | Drug Info | [33] | |||
| 20 | 4-(2-Benzylamino-ethoxy)-1,3-dihydro-indol-2-one | Drug Info | [32] | |||
| 21 | 4-(4-Benzyl-piperazin-1-yl)-1H-benzoimidazole | Drug Info | [34] | |||
| 22 | 4-(4-Benzyl-piperazin-1-yl)-1H-indole | Drug Info | [34] | |||
| 23 | 4-(4-Benzyl-piperazin-1-yl)-5-chloro-1H-indole | Drug Info | [34] | |||
| 24 | 4-(4-Benzyl-piperazin-1-yl)-7-bromo-1H-indole | Drug Info | [34] | |||
| 25 | 4-[2-(2-Benzyl-phenoxy)-ethyl]-morpholine | Drug Info | [1] | |||
| 26 | A-425444 | Drug Info | [35] | |||
| 27 | ABT-670 | Drug Info | [35] | |||
| 28 | Benzyl-[2-(1H-indazol-4-yloxy)-ethyl]-amine | Drug Info | [32] | |||
| 29 | Benzyl-[2-(1H-indol-4-yloxy)-ethyl]-amine | Drug Info | [32] | |||
| 30 | FLUMEZAPINE | Drug Info | [39] | |||
| 31 | FLUTROLINE | Drug Info | [40] | |||
| 32 | ISOCLOZAPINE | Drug Info | [31] | |||
| 33 | ISOLOXAPINE | Drug Info | [41] | |||
| 34 | JL-18 | Drug Info | [42] | |||
| 35 | L-741626 | Drug Info | [43] | |||
| 36 | L-741742 | Drug Info | [44] | |||
| 37 | N-(4-Dipropylaminobutyl)-4-biphenylcarboxamide | Drug Info | [47] | |||
| 38 | N-(4-Propylaminobutyl)-4-biphenylcarboxamide | Drug Info | [47] | |||
| 39 | PG-01037 | Drug Info | [49] | |||
| 40 | QUINPIROLE | Drug Info | [51] | |||
| 41 | SB-271046 | Drug Info | [52] | |||
| 42 | STEPHOLIDINE | Drug Info | [53] | |||
| 43 | UH-232 | Drug Info | [55] | |||
| 44 | [2-(1H-Benzoimidazol-4-yloxy)-ethyl]-benzyl-amine | Drug Info | [32] | |||
| Agonist | [+] 6 Agonist drugs | + | ||||
| 1 | CM-2395 | Drug Info | [16] | |||
| 2 | ABT-724 | Drug Info | [21] | |||
| 3 | A412997 | Drug Info | [36] | |||
| 4 | CP-226269 | Drug Info | [37] | |||
| 5 | FAUC213 | Drug Info | [37] | |||
| 6 | PF-592379 | Drug Info | [48] | |||
| Antagonist | [+] 17 Antagonist drugs | + | ||||
| 1 | L-745,870 | Drug Info | [17], [18] | |||
| 2 | NGD 94-1 | Drug Info | [3], [20] | |||
| 3 | Lu-35138 | Drug Info | [22] | |||
| 4 | PD-165167 | Drug Info | [3] | |||
| 5 | Belaperidone | Drug Info | [3] | |||
| 6 | A-381393 | Drug Info | [17], [18] | |||
| 7 | FAUC 113 | Drug Info | [18] | |||
| 8 | L-750,667 | Drug Info | [45] | |||
| 9 | ML398 | Drug Info | [46] | |||
| 10 | nafadotride | Drug Info | [45] | |||
| 11 | piribedil | Drug Info | [50] | |||
| 12 | RBI257 | Drug Info | [37] | |||
| 13 | Ro 10-4548 | Drug Info | [37] | |||
| 14 | U101958 | Drug Info | [54] | |||
| 15 | [125I]L750667 | Drug Info | [56] | |||
| 16 | [3H]N-methylspiperone | Drug Info | [45] | |||
| 17 | [3H]spiperone | Drug Info | [57], [58] | |||
| Partial agonist | [+] 1 Partial agonist drugs | + | ||||
| 1 | RP5063 | Drug Info | [19] | |||
| Binder | [+] 3 Binder drugs | + | ||||
| 1 | SPI-376 | Drug Info | [3] | |||
| 2 | U-99363E | Drug Info | [3] | |||
| 3 | Sonepiprazole | Drug Info | [3] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Dopaminergic synapse | hsa04728 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Dopaminergic synapse | |||||
| Panther Pathway | [+] 4 Panther Pathways | + | ||||
| 1 | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
| 2 | Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
| 3 | Dopamine receptor mediated signaling pathway | |||||
| 4 | Nicotine pharmacodynamics pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Dopamine receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 8 WikiPathways | + | ||||
| 1 | Hypothetical Network for Drug Addiction | |||||
| 2 | Monoamine GPCRs | |||||
| 3 | GPCRs, Class A Rhodopsin-like | |||||
| 4 | Genes and (Common) Pathways Underlying Drug Addiction | |||||
| 5 | GPCR ligand binding | |||||
| 6 | GPCR downstream signaling | |||||
| 7 | Nicotine Activity on Dopaminergic Neurons | |||||
| 8 | GPCRs, Other | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 ... J Med Chem. 2004 Aug 12;47(17):4155-8. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 38). | |||||
| REF 3 | The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | Pharmaceutical Research Companies Are Developing More Than 300 Medicines to Treat Mental Illnesses. Pharmaceutical Research and Manufacturers of America report.2010. | |||||
| REF 6 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3303). | |||||
| REF 7 | ClinicalTrials.gov (NCT01490086) RP5063 in Subjects With Schizophrenia or Schizoaffective Disorder. U.S. National Institutes of Health. | |||||
| REF 8 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 979). | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019657) | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014237) | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008657) | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006596) | |||||
| REF 13 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 980). | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005975) | |||||
| REF 15 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127) | |||||
| REF 17 | Dopamine 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. | |||||
| REF 18 | Comparative 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. | |||||
| REF 19 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 20 | II. Localization and characterization of dopamine D4 binding sites in rat and human brain by use of the novel, D4 receptor-selective ligand [3H]NGD 94-1. J Pharmacol Exp Ther. 1997 Aug;282(2):1020-7. | |||||
| REF 21 | Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats. Proc Natl Acad Sci U S A. 2004 April 27; 101(17): 6758-6763. | |||||
| REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014237) | |||||
| REF 23 | I. NGD 94-1: identification of a novel, high-affinity antagonist at the human dopamine D4 receptor. J Pharmacol Exp Ther. 1997 Aug;282(2):1011-9. | |||||
| REF 24 | Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71. | |||||
| REF 25 | BIMG 80, a novel potential antipsychotic drug: evidence for multireceptor actions and preferential release of dopamine in prefrontal cortex. J Neurochem. 1997 Jul;69(1):182-90. | |||||
| REF 26 | Effects of YM-43611, a novel dopamine D2-like receptor antagonist, on immediate early gene expression in the rat forebrain. Neuropsychopharmacology. 1997 Jul;17(1):27-33. | |||||
| REF 27 | Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. | |||||
| REF 28 | Conjugated enynes as nonaromatic catechol bioisosteres: synthesis, binding experiments, and computational studies of novel dopamine receptor agonis... J Med Chem. 2000 Feb 24;43(4):756-62. | |||||
| REF 29 | Synthesis and biological investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype. Bioorg Med Chem Lett. 2006 Jun 1;16(11):2955-9. | |||||
| REF 30 | Piperidinylpyrroles: design, synthesis and binding properties of novel and selective dopamine D4 receptor ligands. Bioorg Med Chem Lett. 1999 Nov 1;9(21):3143-6. | |||||
| REF 31 | Affinity of 10-(4-methylpiperazino)dibenz[b,f]oxepins for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1982 Jul;25(7):855-8. | |||||
| REF 32 | New generation dopaminergic agents. 7. Heterocyclic bioisosteres that exploit the 3-OH-phenoxyethylamine D2 template. Bioorg Med Chem Lett. 1999 Sep 6;9(17):2593-8. | |||||
| REF 33 | 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... J Med Chem. 1996 May 10;39(10):1941-2. | |||||
| REF 34 | New generation dopaminergic agents. 5. Heterocyclic bioisosteres that exploit the 3-OH-N1-phenylpiperazine dopaminergic template. Bioorg Med Chem Lett. 1998 Oct 6;8(19):2675-80. | |||||
| REF 35 | 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 ago... J Med Chem. 2006 Dec 14;49(25):7450-65. | |||||
| REF 36 | A-412997 is a selective dopamine D4 receptor agonist in rats. Pharmacol Biochem Behav. 2005 Sep;82(1):140-7. | |||||
| REF 37 | Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme selectivity for the dopamine D4 receptor interact with a common recepto... Mol Pharmacol. 2004 Dec;66(6):1491-9. | |||||
| REF 38 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 217). | |||||
| REF 39 | Effects of conformationally restricted 4-piperazinyl-10H-thienobenzodiazepine neuroleptics on central dopaminergic and cholinergic systems. J Med Chem. 1982 Oct;25(10):1133-40. | |||||
| REF 40 | Neuroleptic activity in 5-aryltetrahydro-gamma-carbolines. J Med Chem. 1980 Jun;23(6):635-43. | |||||
| REF 41 | Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1981 Sep;24(9):1021-6. | |||||
| REF 42 | (S)-(-)-4-[4-[2-(isochroman-1-yl)ethyl]-piperazin-1-yl] benzenesulfonamide, a selective dopamine D4 antagonist. J Med Chem. 1996 Jun 21;39(13):2435-7. | |||||
| REF 43 | Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626. Bioorg Med Chem. 2010 Jul 15;18(14):5291-300. | |||||
| REF 44 | 5-(4-Chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)isoxazole: a potent, selective antagonist at human cloned dopamine D4 receptors. J Med Chem. 1996 May 10;39(10):1943-5. | |||||
| REF 45 | Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology. Mol Pharmacol. 2000 Jan;57(1):144-52. | |||||
| REF 46 | Discovery and Characterization of ML398, a Potent and Selective Antagonist of the D4 Receptor with in Vivo Activity. ACS Med Chem Lett. 2014 Jul 9;5(9):1060-4. | |||||
| REF 47 | Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies. J Med Chem. 2008 Nov 13;51(21):6829-38. | |||||
| REF 48 | Lack of abuse potential in a highly selective dopamine D3 agonist, PF-592,379, in drug self-administration and drug discrimination in rats. Behav Pharmacol. 2012 Jun;23(3):280-91. | |||||
| REF 49 | Heterocyclic analogues of N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)arylcarboxamides with functionalized linking chains as novel dopamine D3... J Med Chem. 2007 Aug 23;50(17):4135-46. | |||||
| REF 50 | Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. | |||||
| REF 51 | Pharmacophore-guided drug discovery investigations leading to bioactive 5-aminotetrahydropyrazolopyridines. Implications for the binding mode of he... J Med Chem. 2005 Sep 8;48(18):5771-9. | |||||
| REF 52 | Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists. Bioorg Med Chem Lett. 2008 Jan 15;18(2):738-43. | |||||
| REF 53 | Dibenzazecine scaffold rebuilding--is the flexibility always essential for high dopamine receptor affinities Bioorg Med Chem. 2009 Oct 1;17(19):6898-907. | |||||
| REF 54 | Substituted 4-aminopiperidines having high in vitro affinity and selectivity for the cloned human dopamine D4 receptor. Eur J Pharmacol. 1997 Mar 19;322(2-3):283-6. | |||||
| REF 55 | (Dipropylamino)-tetrahydronaphthofurans: centrally acting serotonin agonists and dopamine agonists-antagonists, Bioorg. Med. Chem. Lett. 7(21):2759-2764 (1997). | |||||
| REF 56 | Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor. Mol Pharmacol. 1996 Dec;50(6):1658-64. | |||||
| REF 57 | Differential effects of [3H]nemonapride and [3H]spiperone binding on human dopamine D4 receptors. Neurosci Lett. 1995 Feb 17;186(2-3):145-8. | |||||
| REF 58 | Modeling the similarity and divergence of dopamine D2-like receptors and identification of validated ligand-receptor complexes. J Med Chem. 2005 Feb 10;48(3):694-709. | |||||
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