Target Validation Information
Target ID T92609
Target Name Alpha-1A adrenergic receptor
Target Type
Successful
Drug Potency against Target Imidazolidin-2-ylidene-quinoxalin-6-yl-amine Drug Info Ki = 11000 nM
4-(3-Hydroxy-piperidin-3-yl)-benzene-1,2-diol Drug Info Ki = 15000 nM [526729]
RWJ-25730 Drug Info Ki = 8.2 nM [533800]
SNAP-8719 Drug Info Ki = 1400 nM [527512]
1-(2-Chloro-phenyl)-piperazine Drug Info Ki = 710 nM [528039]
(2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amine Drug Info Ki = 6000 nM [534315]
RS-513815 Drug Info Ki = 41 nM [527393]
2-(4-tert-Butyl-phenyl)-4,5-dihydro-1H-imidazole Drug Info Ki = 91 nM [527180]
RWJ-38063 Drug Info Ki = 9.3 nM [527393]
RWJ-68157 Drug Info Ki = 22 nM [527393]
A-315456 Drug Info Ki = 490 nM [527393]
A-119637 Drug Info Ki = 2.6 nM [527393]
RS-100975 Drug Info Ki = 1.3 nM [527393]
NIGULDIPINE Drug Info Ki = 1.8 nM [533638]
RWJ-69736 Drug Info Ki = 0.65 nM [527393]
SK&F-104078 Drug Info Ki = 33 nM [533638]
SNAP-7915 Drug Info Ki = 0.17 nM [527393]
4-(2,3-Dihydro-1H-phenalen-1-yl)-1H-imidazole Drug Info Ki = 55 nM [534160]
1',2',3',6'-Tetrahydro-[2,4']bipyridinyl Drug Info Ki = 4000 nM [533509]
4-(3,4-Dihydro-1H-isoquinolin-2-yl)-quinoline Drug Info Ki = 3200 nM [526618]
4-((Z)-1-Naphthalen-1-yl-propenyl)-1H-imidazole Drug Info Ki = 57 nM [534160]
SK&F-106686 Drug Info Ki = 58 nM [533638]
AGN-193080 Drug Info Ki = 470 nM
4-(4-Methyl-indan-1-yl)-1H-imidazole Drug Info Ki = 73 nM [534467]
RS-100329 Drug Info Ki = 0.25 nM [527393]
SK&F-105854 Drug Info Ki = 3300 nM [527393]
CORYNANTHEINE Drug Info Ki = 29 nM [527393]
RWJ-68141 Drug Info Ki = 59 nM [527393]
UPIDOSIN Drug Info Ki = 1 nM [527393]
AR-129330 Drug Info IC50 = 300 nM [530396]
A-123189 Drug Info Ki = 4.2 nM [527393]
L-771688 Drug Info Ki = 0.36 nM [527393]
SNAP-6201 Drug Info Ki = 0.2 nM [527393]
Ro-11-04253 Drug Info Ki = 5 nM [527393]
A-131701 Drug Info Ki = 0.22 nM [527393]
SNAP-5036 Drug Info Ki = 4.4 nM [527393]
(-)-SNAP-5399 Drug Info Ki = 0.4 nM [527393]
L-765314 Drug Info Ki = 420 nM [527393]
Dutasteride + tamsulosin Drug Info IC50 = 6 nM [552402]
OCTOCLOTHEPIN Drug Info Ki = 0.66 nM [531171]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one Drug Info Ki = 18 nM [531079]
Siramesine Drug Info IC50 = 330 nM [533739]
5-Bromo-8-piperazin-1-yl-imidazo[1,2-a]pyrazine Drug Info Ki = 1490 nM [526778]
4-Benzo[b]thiophen-4-yl-1H-imidazole Drug Info Ki = 343 nM [525720]
Imidazolidin-2-ylidene-o-tolyl-amine Drug Info Ki = 2500 nM
AGN-192172 Drug Info Ki = 8900 nM
R-226161 Drug Info Ki = 125 nM [528772]
ISOCLOZAPINE Drug Info IC50 = 64 nM [534532]
SNAP-94847 Drug Info Ki = 180 nM [528972]
SNAP-5089 Drug Info Ki = 1.3 nM [533638]
1-(2-Methoxy-phenyl)-piperazine Drug Info Ki = 3508 nM [528039]
4-Morpholin-2-yl-benzene-1,2-diol Drug Info Ki = 7400 nM [526729]
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine Drug Info Ki = 490 nM [533509]
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole Drug Info Ki = 536 nM [533805]
4-((E)-1-Naphthalen-1-yl-propenyl)-1H-imidazole Drug Info Ki = 387 nM [534160]
2-Pyridin-4-yl-1,2,3,4-tetrahydro-isoquinoline Drug Info Ki = 5800 nM [526618]
(2-Bromo-phenyl)-(1H-imidazol-2-yl)-amine Drug Info Ki = 11000 nM [534315]
LEVONORDEFRIN Drug Info Ki = 9221 nM [534160]
8-Piperazin-1-yl-imidazo[1,2-a]pyrazine Drug Info Ki = 3100 nM [526778]
UH-301 Drug Info Ki = 6080 nM [534363]
MAZAPERTINE Drug Info Ki = 0.2 nM [533800]
TIOSPIRONE Drug Info Ki = 1.5 nM [534093]
1-(pyridin-2-yl)piperazine Drug Info Ki = 2400 nM [533509]
MEDETOMIDINE Drug Info Ki = 1102 nM [533805]
Sunepitron Drug Info Ki = 35 nM [528210]
(+/-)-nantenine Drug Info Ki = 2 nM [530558]
WB-4101 Drug Info Ki = 0.35 nM [533682]
N-(5-Bromo-quinoxalin-6-yl)-guanidine Drug Info Ki = 17000 nM
NAFTOPIDIL Drug Info Ki = 3.7 nM [527393]
SPIPERONE Drug Info Ki = 7.9 nM [527393]
BP-897 Drug Info Ki = 33 nM [526696]
RX-821002 Drug Info Ki = 27 nM [533375]
BMY-7378 Drug Info Ki = 290 nM [527512]
FLUANISONE Drug Info Ki = 0.87 nM [533378]
4-(1-Naphthalen-1-yl-propyl)-1H-imidazole Drug Info Ki = 574 nM [534160]
SK&F-86466 Drug Info Ki = 449 nM [533638]
SK&F-104856 Drug Info Ki = 36 nM [533638]
4-(1-Naphthalen-1-yl-vinyl)-1H-imidazole Drug Info Ki = 1734 nM [534160]
4-(4-Isopropyl-morpholin-2-yl)-benzene-1,2-diol Drug Info Ki = 6700 nM [526729]
Action against Disease Model Alfuzosin Alfuzosin significantly prolonged action potential duration (APD)(60) in rabbit Purkinje fibers (p < 0.05) and QT in isolated rabbit hearts (p < 0.05) at the clinically relevantconcentration of 300 nM. In man, the QT interval corrected with Fridericia's formula increased 7.7 ms, which exceeds the 5.0-ms threshold for a positive TCQS. Effects on hK(v)11.1, hK(v)4.3, and hK(v)7.1/hKCNE1 potassi uM currents and calci uM current were not involved. At 300 nM, approximately 30x C(max), alfuzosin significantly increased whole-cell peak sodi uM (hNa(v)1.5) current (p < 0.05), increased the probability of late hNa(v)1.5 single-channel openings, and significantly shortened the slow time constant for recovery from inactivation. [552751] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Alpha 1A-AR knockout mice: cardiac development is normal,cardiac function has decreased contraction and pressor response is decreased to PE [552751]
References
Ref 552751Alfuzosin delays cardiac repolarization by a novel mechanism. J Pharmacol Exp Ther. 2008 Feb;324(2):427-33. Epub 2007 Nov 6.
Ref 526729J Med Chem. 1992 Mar 20;35(6):1009-18.Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors.
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 527512J Med Chem. 2005 Apr 21;48(8):3076-9.Synthesis and structure-activity relationship of fluoro analogues of 8-{2-[4-(4-methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as selective alpha(1d)-adrenergic receptor antagonists.
Ref 528039J Med Chem. 1991 Jun;34(6):1850-4.Pyrimido[5,4-b]indole derivatives. 1. A new class of potent and selective alpha 1 adrenoceptor ligands.
Ref 534315J Med Chem. 1997 Jan 3;40(1):18-23.Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527180Bioorg Med Chem Lett. 2004 Sep 20;14(18):4697-9.2-(Anilino)imidazolines and 2-(benzyl)imidazoline derivatives as h5-HT1D serotonin receptor ligands.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 533638J 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.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 533638J 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.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 534160J Med Chem. 1996 Jul 19;39(15):3001-13.Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine.
Ref 533509J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.
Ref 526618Bioorg Med Chem Lett. 2003 May 19;13(10):1759-62.4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor antagonists.
Ref 534160J Med Chem. 1996 Jul 19;39(15):3001-13.Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine.
Ref 533638J 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.
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 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 530396Bioorg 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.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 552402Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate. 2004 Feb 1;58(2):130-44.
Ref 531171J Med Chem. 2010 Oct 14;53(19):7021-34.Exploring the neuroleptic substituent in octoclothepin: potential ligands for positron emission tomography with subnanomolar affinity for |A(1)-adrenoceptors.
Ref 531079J 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.
Ref 533739J Med Chem. 1995 May 26;38(11):1998-2008.Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 1. 3-(omega-aminoalkyl)-1H-indoles.
Ref 526778J Med Chem. 1992 Oct 16;35(21):3845-57.Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines.
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 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 534532J Med Chem. 1997 Dec 5;40(25):4146-53.Synthesis and pharmacological evaluation of triflate-substituted analogues of clozapine: identification of a novel atypical neuroleptic.
Ref 528972J Med Chem. 2007 Aug 9;50(16):3883-90.Synthesis and SAR investigations for novel melanin-concentrating hormone 1 receptor (MCH1) antagonists part 2: A hybrid strategy combining key fragments of HTS hits.
Ref 533638J 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.
Ref 528039J Med Chem. 1991 Jun;34(6):1850-4.Pyrimido[5,4-b]indole derivatives. 1. A new class of potent and selective alpha 1 adrenoceptor ligands.
Ref 526729J Med Chem. 1992 Mar 20;35(6):1009-18.Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors.
Ref 533509J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.
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 534160J Med Chem. 1996 Jul 19;39(15):3001-13.Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine.
Ref 526618Bioorg Med Chem Lett. 2003 May 19;13(10):1759-62.4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor antagonists.
Ref 534315J Med Chem. 1997 Jan 3;40(1):18-23.Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
Ref 534160J Med Chem. 1996 Jul 19;39(15):3001-13.Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine.
Ref 526778J Med Chem. 1992 Oct 16;35(21):3845-57.Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines.
Ref 534363J Med Chem. 1997 Apr 11;40(8):1252-7.N-[2-[(substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines: synthesis and wide range of antagonism at the human 5-HT1A receptor.
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 534093J Med Chem. 1996 Jan 5;39(1):143-8.3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents.
Ref 533509J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.
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 528210J Med Chem. 2006 Jun 1;49(11):3116-35.An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression.
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 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 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 527393Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists.
Ref 526696J 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.
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 527512J Med Chem. 2005 Apr 21;48(8):3076-9.Synthesis and structure-activity relationship of fluoro analogues of 8-{2-[4-(4-methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as selective alpha(1d)-adrenergic receptor antagonists.
Ref 533378J Med Chem. 1987 Nov;30(11):2099-104.2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 1.
Ref 534160J Med Chem. 1996 Jul 19;39(15):3001-13.Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine.
Ref 533638J 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.
Ref 533638J 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.
Ref 534160J Med Chem. 1996 Jul 19;39(15):3001-13.Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine.
Ref 526729J Med Chem. 1992 Mar 20;35(6):1009-18.Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors.

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