Target Information
| Target General Information | Top | |||||
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| Target ID |
T11448
(Former ID: TTDS00032)
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| Target Name |
Adrenergic receptor alpha-2A (ADRA2A)
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| Synonyms |
Alpha-2AAR; Alpha-2A adrenoreceptor; Alpha-2A adrenoceptor; Alpha-2A adrenergic receptor; Alpha-2 adrenergic receptor subtype C10; ADRAR; ADRA2R
Click to Show/Hide
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| Gene Name |
ADRA2A
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Attention deficit hyperactivity disorder [ICD-11: 6A05] | |||||
| 2 | Opioid use disorder [ICD-11: 6C43] | |||||
| 3 | Substance abuse [ICD-11: 6C40] | |||||
| Function |
The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MFRQEQPLAEGSFAPMGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLML
LTVFGNVLVIIAVFTSRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAW CEIYLALDVLFCTSSIVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVIS FPPLISIEKKGGGGGPQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKR RTRVPPSRRGPDAVAAPPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGP RDTDALDLEESSSSDHAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTP AAGPGEERVGAAKASRWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPR TLFKFFFWFGYCNSSLNPVIYTIFNHDFRRAFKKILCRGDRKRIV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A00273 ; BADD_A05198 ; BADD_A06414 ; BADD_A08478 ; BADD_A08611 | |||||
| HIT2.0 ID | T77RFX | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Connexyn | Drug Info | Approved | Attention deficit hyperactivity disorder | [2] | |
| 2 | Lofexidine | Drug Info | Approved | Opioid dependence | [3] | |
| 3 | MOXONIDINE | Drug Info | Approved | Alcohol dependence | [4] | |
| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | A295 | Drug Info | IND submitted | Aggressive cancer | [5] | |
| 2 | Guanfacine | Drug Info | Phase 3 | Alzheimer disease | [6] | |
| 3 | MEDETOMIDINE | Drug Info | Phase 2 | Pain | [7] | |
| 4 | DSP-1200 | Drug Info | Phase 1 | Depression | [8] | |
| Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
| 1 | NMI-870 | Drug Info | Discontinued in Phase 2 | Sexual dysfunction | [9] | |
| 2 | S-18616 | Drug Info | Terminated | Pain | [10] | |
| 3 | SNAP-5089 | Drug Info | Terminated | Heart arrhythmia | [11], [12] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Agonist | [+] 5 Agonist drugs | + | ||||
| 1 | Connexyn | Drug Info | [1] | |||
| 2 | Lofexidine | Drug Info | [3] | |||
| 3 | Guanfacine | Drug Info | [14] | |||
| 4 | Beta-methoxyamphetamine | Drug Info | [43] | |||
| 5 | Chloroethylclonidine | Drug Info | [46] | |||
| Inhibitor | [+] 71 Inhibitor drugs | + | ||||
| 1 | MOXONIDINE | Drug Info | [13] | |||
| 2 | A295 | Drug Info | [5] | |||
| 3 | MEDETOMIDINE | Drug Info | [15] | |||
| 4 | MAZAPERTINE | Drug Info | [16] | |||
| 5 | A-80426 | Drug Info | [18] | |||
| 6 | SK&F-104078 | Drug Info | [20] | |||
| 7 | SNAP-5089 | Drug Info | [21] | |||
| 8 | WB-4101 | Drug Info | [22] | |||
| 9 | (+/-)-nantenine | Drug Info | [23] | |||
| 10 | (1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol | Drug Info | [24] | |||
| 11 | (1H-Benzoimidazol-5-yl)-(1H-imidazol-2-yl)-amine | Drug Info | [25] | |||
| 12 | (1H-Imidazol-2-yl)-quinoxalin-6-yl-amine | Drug Info | [25] | |||
| 13 | (2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amine | Drug Info | [25] | |||
| 14 | (2-Bromo-phenyl)-(1H-imidazol-2-yl)-amine | Drug Info | [25] | |||
| 15 | (2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [26] | |||
| 16 | (3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [26] | |||
| 17 | (3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [26] | |||
| 18 | (R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [27] | |||
| 19 | (S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [27] | |||
| 20 | 1',2',3',6'-Tetrahydro-[2,4']bipyridinyl | Drug Info | [28] | |||
| 21 | 1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline | Drug Info | [29] | |||
| 22 | 1,2,3,4,5,6-Hexahydro-benzo[c]azocine | Drug Info | [27] | |||
| 23 | 1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol | Drug Info | [30] | |||
| 24 | 1,2,3,4-Tetrahydro-isoquinolin-7-ol | Drug Info | [30] | |||
| 25 | 1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole | Drug Info | [31] | |||
| 26 | 1,2,3,4-tetrahydroisoquinoline | Drug Info | [32] | |||
| 27 | 1-((S)-2-aminopropyl)-1H-indazol-6-ol | Drug Info | [33] | |||
| 28 | 1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine | Drug Info | [28] | |||
| 29 | 1-(pyridin-2-yl)piperazine | Drug Info | [28] | |||
| 30 | 2,3,4,5-Tetrahydro-1H-benzo[c]azepine | Drug Info | [27] | |||
| 31 | 2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine | Drug Info | [27] | |||
| 32 | 2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine | Drug Info | [27] | |||
| 33 | 2,3-Dihydro-1H-isoindole | Drug Info | [27] | |||
| 34 | 2-BFi | Drug Info | [34] | |||
| 35 | 3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [35] | |||
| 36 | 3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [24] | |||
| 37 | 3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [27] | |||
| 38 | 3-Methyl-7-nitro-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [36] | |||
| 39 | 4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole | Drug Info | [15] | |||
| 40 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [37] | |||
| 41 | 4-(4-Methyl-indan-1-yl)-1H-imidazole | Drug Info | [38] | |||
| 42 | 4-Benzo[b]thiophen-4-yl-1H-imidazole | Drug Info | [39] | |||
| 43 | 5-Aminomethyl-naphthalen-2-ol | Drug Info | [30] | |||
| 44 | 6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene | Drug Info | [27] | |||
| 45 | 7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline | Drug Info | [40] | |||
| 46 | 7-Nitro-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [36] | |||
| 47 | 8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline | Drug Info | [30] | |||
| 48 | AKUAMMIGINE | Drug Info | [41] | |||
| 49 | AR-129330 | Drug Info | [42] | |||
| 50 | Butyl-indol-1-yl-pyridin-4-yl-amine | Drug Info | [26] | |||
| 51 | C-(6-Methoxy-naphthalen-1-yl)-methylamine | Drug Info | [30] | |||
| 52 | C-Naphthalen-1-yl-methylamine | Drug Info | [30] | |||
| 53 | Ethyl-indol-1-yl-pyridin-4-yl-amine | Drug Info | [26] | |||
| 54 | GNF-PF-2857 | Drug Info | [48] | |||
| 55 | GNF-PF-3878 | Drug Info | [48] | |||
| 56 | Indol-1-yl-methyl-pyridin-4-yl-amine | Drug Info | [26] | |||
| 57 | Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine | Drug Info | [26] | |||
| 58 | Indol-1-yl-pyridin-4-yl-amine | Drug Info | [26] | |||
| 59 | JP1302 | Drug Info | [48] | |||
| 60 | METHYLNORADRENALINE | Drug Info | [22] | |||
| 61 | MEZILAMINE | Drug Info | [49] | |||
| 62 | PIPEROXAN | Drug Info | [22] | |||
| 63 | R-226161 | Drug Info | [50] | |||
| 64 | S-34324 | Drug Info | [18] | |||
| 65 | SK&F-29661 | Drug Info | [36] | |||
| 66 | SK&F-64139 | Drug Info | [32] | |||
| 67 | SNAP-5150 | Drug Info | [21] | |||
| 68 | TRACIZOLINE | Drug Info | [40] | |||
| 69 | Tramazoline | Drug Info | [22] | |||
| 70 | TRYPTOLINE | Drug Info | [40] | |||
| 71 | [3H]RX821002 | Drug Info | [51] | |||
| Antagonist | [+] 3 Antagonist drugs | + | ||||
| 1 | DSP-1200 | Drug Info | [8] | |||
| 2 | BRL 44408 | Drug Info | [44], [45] | |||
| 3 | Ciproxifan | Drug Info | [47] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | NMI-870 | Drug Info | [17] | |||
| 2 | S-18616 | Drug Info | [19] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Brimonidine | Ligand Info | |||||
| Structure Description | Structure of the alpha2A-adrenergic receptor GoA signaling complex bound to brimonidine | PDB:7EJ8 | ||||
| Method | Electron microscopy | Resolution | 3.00 Å | Mutation | No | [52] |
| PDB Sequence |
YSLQVTLTLV
52 CLAGLLMLLT62 VFGNVLVIIA72 VFTSRALKAP82 QNLFLVSLAS92 ADILVATLVI 102 PFSLANEVMG112 YWYFGKAWCE122 IYLALDVLFC132 TSSIVHLCAI142 SLDRYWSITQ 152 AIEYNLKRTP162 RRIKAIIITV172 WVISAVISFP182 PRCEINDQKW210 YVISSCIGSF 220 FAPCLIMILV230 YVRIYQIAKR240 RTRRGRQNRE384 KRFTFVLAVV394 IGVFVVCWFP 404 FFFTYTLTAV414 GCSVPRTLFK424 FFFWFGYCNS434 SLNPVIYTIF444 NHDFRRAFKK 454 ILC
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| Ligand Name: Norepinephrine | Ligand Info | |||||
| Structure Description | Structure of the alpha2A-adrenergic receptor GoA signaling complex | PDB:7EJ0 | ||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | No | [52] |
| PDB Sequence |
QVTLTLVCLA
55 GLLMLLTVFG65 NVLVIIAVFT75 SRALKAPQNL85 FLVSLASADI95 LVATLVIPFS 105 LANEVMGYWY115 FGKAWCEIYL125 ALDVLFCTSS135 IVHLCAISLD145 RYWSITQAIE 155 YNLKRTPRRI165 KAIIITVWVI175 SAVISFPPLR202 CEINDQKWYV212 ISSCIGSFFA 222 PCLIMILVYV232 RIYQIAKRRT242 RGRQNREKRF387 TFVLAVVIGV397 FVVCWFPFFF 407 TYTLTAVGCS417 VPRTLFKFFF427 WFGYCNSSLN437 PVIYTIFNHD447 FRRAFKKILC 457
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
Human Pathway Affiliation
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| cGMP-PKG signaling pathway | hsa04022 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | 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 | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | cGMP-PKG signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Alpha adrenergic receptor signaling pathway | |||||
| Reactome | [+] 6 Reactome Pathways | + | ||||
| 1 | Adrenoceptors | |||||
| 2 | Adrenaline signalling through Alpha-2 adrenergic receptor | |||||
| 3 | Adrenaline,noradrenaline inhibits insulin secretion | |||||
| 4 | G alpha (i) signalling events | |||||
| 5 | G alpha (z) signalling events | |||||
| 6 | Surfactant metabolism | |||||
| WikiPathways | [+] 6 WikiPathways | + | ||||
| 1 | Monoamine GPCRs | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Platelet Aggregation (Plug Formation) | |||||
| 4 | Integration of energy metabolism | |||||
| 5 | GPCR ligand binding | |||||
| 6 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009 Sep 29;163(1):339-51. | |||||
| REF 2 | Shire Announces NDA Submission of Guanfacine Extended Release for the Treatment of ADHD in Children and Adolescents, 2009. FDA Approved - September 2, 2009 | |||||
| REF 3 | 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89. | |||||
| REF 4 | The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat ... J Pharmacol Exp Ther. 2003 Aug;306(2):646-57. | |||||
| REF 5 | Clinical pipeline report, company report or official report of Klus Pharma | |||||
| REF 6 | ClinicalTrials.gov (NCT03116126) Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease. U.S.National Institutes of Health. | |||||
| REF 7 | Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves. Am J Vet Res. 2008 Mar;69(3):319-29. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| 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 800014166) | |||||
| 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 800007941) | |||||
| REF 11 | 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: 498). | |||||
| 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 800006771) | |||||
| REF 13 | Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5. | |||||
| REF 14 | Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13. | |||||
| REF 15 | A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33. | |||||
| REF 16 | A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem. 1994 Apr 15;37(8):1060-2. | |||||
| REF 17 | Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges. Cardiovasc Hematol Agents Med Chem. 2009 October; 7(4): 260-269. | |||||
| REF 18 | 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 19 | S18616, a highly potent spiroimidazoline agonist at alpha(2)-adrenoceptors: II. Influence on monoaminergic transmission, motor function, and anxiety in comparison with dexmedetomidine and clonidine. J Pharmacol Exp Ther. 2000 Dec;295(3):1206-22. | |||||
| REF 20 | Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. J Med Chem. 1995 Sep 1;38(18):3415-44. | |||||
| REF 21 | Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8. | |||||
| REF 22 | alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. J Med Chem. 1982 Dec;25(12):1389-401. | |||||
| REF 23 | Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. | |||||
| REF 24 | 3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferas... J Med Chem. 1999 Jun 3;42(11):1982-90. | |||||
| REF 25 | Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. J Med Chem. 1997 Jan 3;40(1):18-23. | |||||
| REF 26 | Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeu... J Med Chem. 1996 Jan 19;39(2):570-81. | |||||
| REF 27 | Effect of ring size or an additional heteroatom on the potency and selectivity of bicyclic benzylamine-type inhibitors of phenylethanolamine N-meth... J Med Chem. 1996 Aug 30;39(18):3539-46. | |||||
| REF 28 | Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. J Med Chem. 1984 Sep;27(9):1182-5. | |||||
| REF 29 | N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies. J Med Chem. 1998 Oct 8;41(21):4165-70. | |||||
| REF 30 | Examination of the role of the acidic hydrogen in imparting selectivity of 7-(aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) toward inh... J Med Chem. 1997 Dec 5;40(25):3997-4005. | |||||
| REF 31 | Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I(2) receptor ligands. Bioorg Med Chem Lett. 2004 Feb 23;14(4):1003-5. | |||||
| REF 32 | Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phen... J Med Chem. 2006 Sep 7;49(18):5424-33. | |||||
| REF 33 | 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. J Med Chem. 2006 Jan 12;49(1):318-28. | |||||
| REF 34 | Probes for imidazoline binding sites: synthesis and evaluation of a selective, irreversible I2 ligand. Bioorg Med Chem Lett. 2000 Mar 20;10(6):605-7. | |||||
| REF 35 | 3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline inhibitors of phenylethanolamine N-methyltransferase that display re... J Med Chem. 2005 Jan 13;48(1):134-40. | |||||
| REF 36 | Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoqui... Bioorg Med Chem Lett. 2005 Feb 15;15(4):1143-7. | |||||
| REF 37 | 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 rec... J Med Chem. 2010 Sep 9;53(17):6386-97. | |||||
| REF 38 | Medetomidine analogs as alpha 2-adrenergic ligands. 3. Synthesis and biological evaluation of a new series of medetomidine analogs and their potent... J Med Chem. 1997 Sep 12;40(19):3014-24. | |||||
| REF 39 | Alpha(2) adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-imidazo)-1,3-dimethyl-6,7-dihydro-thianaphthene as a high-affini... J Med Chem. 2000 Apr 6;43(7):1423-6. | |||||
| REF 40 | Binding of an imidazopyridoindole at imidazoline I2 receptors. Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9. | |||||
| REF 41 | Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. J Med Chem. 1995 Sep 15;38(19):3681-716. | |||||
| REF 42 | Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1. Bioorg Med Chem Lett. 2005 Sep 1;15(17):3853-6. | |||||
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