Therapeutic Targets Database
BIDD Pharmainformatics Databases


Target Validation Information
Target NameAlpha-2A adrenergic receptor    
Type of TargetSuccessful target    
Drug Potency against TargetBrimonidinepKi = 6.76[1]
ATC-0175IC50 = 104 nM[2]
Ethyl-indol-1-yl-pyridin-4-yl-amineIC50 = 110 nM[3]
1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinolineIC50 = 130 nM[4]
(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amineIC50 = 2300 nM[3]
Indol-1-yl-methyl-pyridin-4-yl-amineIC50 = 24 nM[3]
(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amineIC50 = 2500 nM[3]
Yohimbine HydrochlorideIC50 = 3.67 nM[5]
Indol-1-yl-propyl-pyridin-4-yl-amineIC50 = 330 nM[3]
(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amineIC50 = 3600 nM[3]
Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amineIC50 = 500 nM[3]
Butyl-indol-1-yl-pyridin-4-yl-amineIC50 = 630 nM[3]
AR-129330IC50 = 7.7 nM[6]
AR-129330IC50 = 7.7 nM[7]
Indol-1-yl-pyridin-4-yl-amineIC50 = 8 nM[3]
RX-821002Ki = 0.36 nM[8]
2,3,4,5-Tetrahydro-1H-benzo[c]azepineKi = 11000 nM[9]
MEZILAMINEKi = 12 nM[10]
AKUAMMIGINEKi = 1210 nM[11]
(+/-)-nantenineKi = 1288 nM[12]
1',2',3',6'-Tetrahydro-[2,4']bipyridinylKi = 144 nM[13]
MOXONIDINEKi = 150 nM[14]
C-Naphthalen-1-yl-methylamineKi = 1600 nM[15]
1,2,3,4,5,6-Hexahydro-benzo[c]azocineKi = 16000 nM[9]
2-Benzofuran-2-yl-4,5-dihydro-1H-imidazoleKi = 1900 nM[18]
A-80426Ki = 2.5 nM[19]
4-Benzo[b]thiophen-4-yl-1H-imidazoleKi = 2.6 nM[20]
WB-4101Ki = 200 nM[21]
SK&F-64139;SK-64139Ki = 21 nM[22]
(2-Bromo-phenyl)-(1H-imidazol-2-yl)-amineKi = 210 nM[23]
5-Aminomethyl-naphthalen-2-olKi = 2100 nM[15]
1,2,3,4-Tetrahydro-isoquinolin-7-olKi = 2200 nM[15]
1-((S)-2-aminopropyl)-1H-indazol-6-olKi = 2270 nM[24]
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazoleKi = 24 nM[17]
SNAP-5089Ki = 2417 nM[25]
2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepineKi = 2600 nM[9]
3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinolineKi = 2800 nM[26]
R-226161Ki = 3.4 nM[27]
(1H-Imidazol-2-yl)-quinoxalin-6-yl-amineKi = 3100 nM[23]
SK&F-104078;SK-104078Ki = 313 nM[28]
7-Nitro-1,2,3,4-tetrahydro-isoquinolineKi = 3200 nM[29]
GNF-PF-3427Ki = 3200 nM[30]
SK&F-29661;SK-29661Ki = 3400 nM[29]
1,2,3,4-tetrahydroisoquinolineKi = 350 nM[22]
GNF-PF-3878Ki = 3600 nM[30]
SNAP-5150Ki = 369 nM[25]
1-Pyridin-2-yl-piperazineKi = 37 nM[13]
3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinolineKi = 3800 nM[31]
TRAMAZOLINEKi = 4.2 nM[21]
2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepineKi = 4100 nM[9]
6,7,8,9-Tetrahydro-5-thia-8-aza-benzocyclohepteneKi = 4600 nM[9]
C-(6-Methoxy-naphthalen-1-yl)-methylamineKi = 4600 nM[15]
3-Methyl-7-nitro-1,2,3,4-tetrahydro-isoquinolineKi = 4840 nM[29]
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazineKi = 5 nM[13]
S-34324Ki = 5.9 nM[19]
1,2,3,4-Tetrahydro-pyrazino[1,2-a]indoleKi = 516 nM[32]
(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinolineKi = 520 nM[9]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-oneKi = 530 nM[33]
(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinolineKi = 6200 nM[9]
(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanolKi = 6600 nM[26]
TRYPTOLINEKi = 710 nM[34]
GNF-PF-2857Ki = 720 nM[30]
TRACIZOLINEKi = 7413 nM[34]
(1H-Benzoimidazol-5-yl)-(1H-imidazol-2-yl)-amineKi = 76 nM[23]
1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-olKi = 78 nM[15]
4-(4-Methyl-indan-1-yl)-1H-imidazoleKi = 8.8 nM[35]
2,3-Dihydro-1H-isoindoleKi = 820 nM[9]
3-Methyl-1,2,3,4-tetrahydro-isoquinolineKi = 840 nM[9]
8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinolineKi = 840 nM[15]
7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carbolineKi = 8840 nM[34]
BP-897Ki = 89 nM[36]
(2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amineKi = 95 nM[23]
PIPEROXANKi = 95 nM[21]
Ref 1Curr Top Med Chem. 2007;7(2):163-86.Agonists and antagonists targeting the different alpha2-adrenoceptor subtypes. To Reference
Ref 2Bioorg Med Chem Lett. 2009 Nov 1;19(21):6166-71. Epub 2009 Sep 6.Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation. To Reference
Ref 3J Med Chem. 1996 Jan 19;39(2):570-81.Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeutic agents for Alzheimer's disease. To Reference
Ref 4J Med Chem. 1998 Oct 8;41(21):4165-70.N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies. To Reference
Ref 5J Med Chem. 2009 Dec 10;52(23):7397-409.Further studies on arylpiperazinyl alkyl pyridazinones: discovery of an exceptionally potent, orally active, antinociceptive agent in thermally induced pain. To Reference
Ref 6Bioorg Med Chem Lett. 2005 Sep 1;15(17):3853-6.Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1. To Reference
Ref 7Bioorg Med Chem Lett. 2005 May 16;15(10):2565-9.Discovery of 4-(dimethylamino)quinazolines as potent and selective antagonists for the melanin-concentrating hormone receptor 1. To Reference
Ref 8J Med Chem. 1986 Oct;29(10):2000-3.Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists. To Reference
Ref 9J Med Chem. 1996 Aug 30;39(18):3539-46.Effect of ring size or an additional heteroatom on the potency and selectivity of bicyclic benzylamine-type inhibitors of phenylethanolamine N-methyltransferase. To Reference
Ref 10J Med Chem. 1986 Aug;29(8):1394-8.4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for alpha 2-adrenoceptors. To Reference
Ref 11J Med Chem. 1995 Sep 15;38(19):3681-716.Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. To Reference
Ref 12Bioorg 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 13J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. To Reference
Ref 14J Med Chem. 1996 Mar 15;39(6):1193-5.Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. To Reference
Ref 15J Med Chem. 1997 Dec 5;40(25):3997-4005.Examination of the role of the acidic hydrogen in imparting selectivity of 7-(aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) toward inhibition of phenylethanolamine N-methyltransferase vs the alpha 2-adrenoceptor. To Reference
Ref 16J Med Chem. 1994 Apr 15;37(8):1060-2.A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. To Reference
Ref 17J Med Chem. 1994 Jul 22;37(15):2328-33.A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic receptors. To Reference
Ref 18Bioorg Med Chem Lett. 2000 Mar 20;10(6):605-7.Probes for imidazoline binding sites: synthesis and evaluation of a selective, irreversible I2 ligand. To Reference
Ref 19J 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 20J Med Chem. 2000 Apr 6;43(7):1423-6.Alpha(2) adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-imidazo)-1,3-dimethyl-6,7-dihydro-thianaphthene as a high-affinity ligand for the alpha(2D) adrenergic receptor. To Reference
Ref 21J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. To Reference
Ref 22J Med Chem. 2006 Sep 7;49(18):5424-33.Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase. To Reference
Ref 23J Med Chem. 1997 Jan 3;40(1):18-23.Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. To Reference
Ref 24J Med Chem. 2006 Jan 12;49(1):318-28.1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. To Reference
Ref 25Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.Design and synthesis of novel dihydropyridine alpha-1a antagonists. To Reference
Ref 26J Med Chem. 1999 Jun 3;42(11):1982-90.3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferase versus the alpha2-adrenoceptor. To Reference
Ref 27Bioorg Med Chem. 2007 Jun 1;15(11):3649-60. Epub 2007 Mar 21.Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism. To Reference
Ref 28J Med Chem. 1995 Sep 1;38(18):3415-44.Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. To Reference
Ref 29Bioorg Med Chem Lett. 2005 Feb 15;15(4):1143-7.Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines. To Reference
Ref 30J Med Chem. 2006 Oct 19;49(21):6351-63.Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists. To Reference
Ref 31J Med Chem. 2005 Jan 13;48(1):134-40.3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline inhibitors of phenylethanolamine N-methyltransferase that display remarkable potency and selectivity. To Reference
Ref 32Bioorg Med Chem Lett. 2004 Feb 23;14(4):1003-5.Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I(2) receptor ligands. To Reference
Ref 33J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference
Ref 34Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors. To Reference
Ref 35J Med Chem. 1997 Sep 12;40(19):3014-24.Medetomidine analogs as alpha 2-adrenergic ligands. 3. Synthesis and biological evaluation of a new series of medetomidine analogs and their potential binding interactions with alpha 2-adrenoceptors involving a "methyl pocket". To Reference
Ref 36J Med Chem. 2003 Aug 28;46(18):3822-39.Synthesis and pharmacological evaluation of potent and highly selective D3 receptor ligands: inhibition of cocaine-seeking behavior and the role of dopamine D3/D2 receptors. To Reference


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