{"id":13389,"date":"2023-02-13T11:01:10","date_gmt":"2023-02-13T11:01:10","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=13389"},"modified":"2024-01-11T11:01:28","modified_gmt":"2024-01-11T11:01:28","slug":"2023-synthesis-and-pharmacological-characterization-of-a-difluorinated-analogue-of-reduced-haloperidol-as-a-sigma-1-receptor-ligand","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2023-synthesis-and-pharmacological-characterization-of-a-difluorinated-analogue-of-reduced-haloperidol-as-a-sigma-1-receptor-ligand\/","title":{"rendered":"2023 &#8211; Synthesis and Pharmacological Characterization of a Difluorinated Analogue of Reduced Haloperidol as a Sigma-1 Receptor Ligand"},"content":{"rendered":"<p>Reduced haloperidol (<b>1<\/b>) was previously reported to act as a potent sigma-1 receptor (S1R) ligand with substantially lower affinity to the dopamine D2 receptor (D2R) compared to haloperidol. It was also found to facilitate brain-derived neurotrophic factor (BDNF) secretion from astrocytic glial cell lines in a sigma-1 receptor (S1R)-dependent manner. Although an increase in BDNF secretion may have beneficial effects in some neurological conditions, the therapeutic utility of reduced haloperidol (<b>1<\/b>) is limited because it can be oxidized back to haloperidol in the body, a potent dopamine D2 receptor antagonist associated with well-documented adverse effects. A difluorinated analogue of reduced haloperidol, (\u00b1)-4-(4-chlorophenyl)-1-(3,3-difluoro-4-(4-fluorophenyl)-4-hydroxybutyl)piperidin-4-ol (<b>2<\/b>), was synthesized in an attempt to minimize the oxidation. Compound (\u00b1)-<b>2<\/b>\u00a0was found to exhibit high affinity to S1R and facilitate BDNF release from mouse brain astrocytes. It was also confirmed that compound\u00a0<b>2<\/b>\u00a0cannot be oxidized back to the corresponding haloperidol analogue in liver microsomes. Furthermore, compound\u00a0<b>2<\/b>\u00a0was distributed to the brain following intraperitoneal administration in mice and reversed the learning deficits in active avoidance tasks. These findings suggest that compound\u00a0<b>2<\/b>\u00a0could serve as a promising S1R ligand with therapeutic potential for the treatment of cognitive impairments.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[54,55],"target_categories":[61],"target_families":[333],"targets":[92],"resource_keyword":[],"class_list":["post-13389","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-cardiac-safety-cipa","therapeutic_areas-cns","target_categories-voltage-gated-ion-channels","target_families-kv-channels","targets-kv11-1-herg"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/13389","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=13389"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=13389"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=13389"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=13389"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=13389"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=13389"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=13389"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=13389"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=13389"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}