Target Validation Information
Target ID T41580
Target Name Alpha-2B adrenergic receptor
Target Type
Successful
Drug Potency against Target (1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol Drug Info Ki = 6600 nM [525507]
1,2,3,4-tetrahydroisoquinoline Drug Info Ki = 350 nM [528403]
7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline Drug Info Ki = 8840 nM [526918]
RX-821002 Drug Info Ki = 0.36 nM [533375]
SNAP-5150 Drug Info Ki = 420 nM [525611]
2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine Drug Info Ki = 4100 nM [534195]
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine Drug Info Ki = 5 nM [533509]
4-Benzo[b]thiophen-4-yl-1H-imidazole Drug Info Ki = 663 nM [525720]
MOXONIDINE Drug Info Ki = 1000 nM [534128]
1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline Drug Info IC50 = 130 nM [534719]
MEZILAMINE Drug Info Ki = 12 nM [533406]
PIPEROXAN Drug Info Ki = 95 nM [533545]
TRAMAZOLINE Drug Info Ki = 4.2 nM [533545]
GNF-PF-3878 Drug Info Ki = 1200 nM [528472]
1-(pyridin-2-yl)piperazine Drug Info Ki = 37 nM [533509]
GNF-PF-3427 Drug Info Ki = 1500 nM [528472]
METHYLNORADRENALINE Drug Info Ki = 7.7 nM [533545]
TRYPTOLINE Drug Info Ki = 710 nM [526918]
1,2,3,4,5,6-Hexahydro-benzo[c]azocine Drug Info Ki = 16000 nM [534195]
5-Aminomethyl-naphthalen-2-ol Drug Info Ki = 2100 nM [534531]
(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine Drug Info IC50 = 2300 nM [534087]
Butyl-indol-1-yl-pyridin-4-yl-amine Drug Info IC50 = 630 nM [534087]
(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline Drug Info Ki = 6200 nM [534195]
3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline Drug Info Ki = 2800 nM [525507]
1',2',3',6'-Tetrahydro-[2,4']bipyridinyl Drug Info Ki = 144 nM [533509]
S-34324 Drug Info Ki = 23 nM [527481]
GNF-PF-2857 Drug Info Ki = 3800 nM [528472]
2,3,4,5-Tetrahydro-1H-benzo[c]azepine Drug Info Ki = 11000 nM [534195]
1,2,3,4-Tetrahydro-isoquinolin-7-ol Drug Info Ki = 2200 nM [534531]
Ethyl-indol-1-yl-pyridin-4-yl-amine Drug Info IC50 = 110 nM [534087]
C-Naphthalen-1-yl-methylamine Drug Info Ki = 1600 nM [534531]
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole Drug Info Ki = 24 nM [533805]
WB-4101 Drug Info Ki = 200 nM [533545]
6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene Drug Info Ki = 4600 nM [534195]
1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol Drug Info Ki = 78 nM [534531]
Indol-1-yl-methyl-pyridin-4-yl-amine Drug Info IC50 = 24 nM [534087]
Indol-1-yl-pyridin-4-yl-amine Drug Info IC50 = 8 nM [534087]
4-(4-Methyl-indan-1-yl)-1H-imidazole Drug Info Ki = 8.8 nM [534467]
(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline Drug Info Ki = 520 nM [534195]
1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole Drug Info Ki = 516 nM [526994]
2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine Drug Info Ki = 2600 nM [534195]
Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine Drug Info IC50 = 500 nM [534087]
8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline Drug Info Ki = 840 nM [534531]
2,3-Dihydro-1H-isoindole Drug Info Ki = 820 nM [534195]
Indol-1-yl-propyl-pyridin-4-yl-amine Drug Info IC50 = 330 nM [534087]
SK&F-64139 Drug Info Ki = 21 nM [528403]
(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine Drug Info IC50 = 2500 nM [534087]
3-Methyl-1,2,3,4-tetrahydro-isoquinoline Drug Info Ki = 840 nM [534195]
TRACIZOLINE Drug Info Ki = 7413 nM [526918]
(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine Drug Info IC50 = 3600 nM [534087]
C-(6-Methoxy-naphthalen-1-yl)-methylamine Drug Info Ki = 4600 nM [534531]
2-BFi Drug Info Ki = 1900 nM [525733]
A-80426 Drug Info Ki = 11 nM [527481]
SNAP-5089 Drug Info Ki = 1088 nM [525611]
MEDETOMIDINE Drug Info Ki = 19 nM [533805]
SK&F-104078 Drug Info Ki = 142 nM [533682]
MAZAPERTINE Drug Info Ki = 17 nM [533800]
(+/-)-nantenine Drug Info Ki = 252 nM [530558]
R-226161 Drug Info Ki = 8.4 nM [528772]
INDORAMIN Drug Info Ki = 528 nM [533682]
3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline Drug Info Ki = 3800 nM [527365]
Action against Disease Model AGN-199981 The compound involved is believed to be AgN-199981, an a2b-adrenergic agonist that was a highly potent and selective analgesic in animal models of neuropathic pain. Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Alpha 2A adrenergic receptor knockout mouse (alpha 2A-KO) showed an increase in sympathetic activity with resting tachycardia, depletion of cardiac tissue norepinephrine concentration. Knockout mouse study reveals that the alpha 2B adrenoceptor (alpha 2B AR) mediates the hypertensive response, and the alpha 2A AR mediates the hypotensive response, induced by alpha 2 agonists. Both the alpha 2A and alpha 2C AR subtypes are required for normal presynaptic control of transmitter release from sympathetic nerves. alpha 2A AR subtype inhibits transmitter release at high stimulation frequencies, whereas the alpha 2C AR subtype modulates neurotransmission at lower levels of nerve activity. Salt-induced hypertension experiment using alpha 2B-KO and alpha 2C-KO revealed that alpha 2B AR subtype is necessary to raise BP in response to dietary salt loading. Lack of adequately functional renal alpha 2B AR is thought to preclude reabsorption of sodi uM. [525507]
References
Ref 525507J 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.
Ref 528403J 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 phenylethanolamineN-methyltransferase.
Ref 526918Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors.
Ref 533375J Med Chem. 1986 Oct;29(10):2000-3.Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists.
Ref 525611Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.Design and synthesis of novel dihydropyridine alpha-1a antagonists.
Ref 534195J 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.
Ref 533509J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.
Ref 525720J Med Chem. 2000 Mar 9;43(5):765-8.alpha(2) Adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-Imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene [corrected] as a high-affinity ligand for the alpha(2D) adrenergic receptor.
Ref 534128J 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.
Ref 534719J Med Chem. 1998 Oct 8;41(21):4165-70.N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies.
Ref 533406J Med Chem. 1986 Aug;29(8):1394-8.4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for alpha 2-adrenoceptors.
Ref 533545J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs.
Ref 533545J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs.
Ref 528472J Med Chem. 2006 Oct 19;49(21):6351-63.Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists.
Ref 533509J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.
Ref 528472J Med Chem. 2006 Oct 19;49(21):6351-63.Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists.
Ref 533545J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs.
Ref 526918Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors.
Ref 534195J 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.
Ref 534531J 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.
Ref 534087J 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.
Ref 534087J 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.
Ref 534195J 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.
Ref 525507J 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.
Ref 533509J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.
Ref 527481J 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.
Ref 528472J Med Chem. 2006 Oct 19;49(21):6351-63.Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists.
Ref 534195J 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.
Ref 534531J 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.
Ref 534087J 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.
Ref 534531J 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.
Ref 533805J 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.
Ref 533545J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs.
Ref 534195J 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.
Ref 534531J 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.
Ref 534087J 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.
Ref 534087J 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.
Ref 534467J 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".
Ref 534195J 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.
Ref 526994Bioorg 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.
Ref 534195J 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.
Ref 534087J 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.
Ref 534531J 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.
Ref 534195J 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.
Ref 534087J 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.
Ref 528403J 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 phenylethanolamineN-methyltransferase.
Ref 534087J 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.
Ref 534195J 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.
Ref 526918Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors.
Ref 534087J 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.
Ref 534531J 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.
Ref 525733Bioorg Med Chem Lett. 2000 Mar 20;10(6):605-7.Probes for imidazoline binding sites: synthesis and evaluation of a selective, irreversible I2 ligand.
Ref 527481J 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.
Ref 525611Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.Design and synthesis of novel dihydropyridine alpha-1a antagonists.
Ref 533805J 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.
Ref 533682J 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.
Ref 533800J 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.
Ref 530558Bioorg 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.
Ref 528772Bioorg 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.
Ref 533682J 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.
Ref 527365J 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.

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