34849-57-5Relevant articles and documents
Structure-activity relationships for a novel series of dopamine D2-like receptor ligands based on N-substituted 3-aryl-8-azabicyclo[3.2.1]octan-3-ol
Paul, Noel M.,Taylor, Michelle,Kumar, Rakesh,Deschamps, Jeffrey R.,Luedtke, Robert R.,Newman, Amy Hauck
experimental part, p. 6095 - 6109 (2009/10/01)
Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; K i(D2R/D3R) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2LR- or hD3R-transfected HEK 293 cells (31, Ki(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, Ki(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes.
N,N-SUBSTITUTED CYCLIC AMINE DERIVATIVES
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, (2008/06/13)
N,N-substituted cyclic amine derivatives represented by general formula (VIII) or pharmacologically acceptable salts thereof: wherein A represents aryl, etc.; E represents -CO- or -CHOH-; G represents oxygen, etc.; J represents optionally substituted aryl; R1 represents lower alkyl, etc.; Alk represents linear or branched lower alkylene; n, v, w, x and y independently represent each 0 or 1; and p represents 2 or 3. These compounds or salts thereof are efficacious in treating diseases against which calcium antagonism is efficacious. These diseases include cerebrovascular disorder at the acute stage, cerebral stroke, cerebral infarction, head injury, cerebral nerve cell death, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, brain circulatory disturbance, brain function disturbance, pain, convulsion, schizophrenia, hemicrania, epilepsy, circular psychosis, nerve degeneration diseases, brain ischemia, AIDS, complex dementia, edema, anxiety and diabetic nephropathy.
