FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2768777112> ?p ?o ?g. }

• W2768777112 abstract "The endocannabinoid system which consists of CB1 and CB2 receptors that belong to type A GPCRs, endogenous cannabinoids (endocannabinoids) and enzyme machinery involved in their biosynthesis, transportation and metabolism is associated with pathophysiology of plethora of disorders ranging from obesity, multiple sclerosis, anorexia nervosa and Huntington's disease. A large number of orthosteric ligands have been developed for CB1 receptors for the treatment of various disorders, but their therapeutic applications are limited due to the problems such as receptor desensitization and CNS side effects. CB1 allosteric modulators have the potential of offering same therapeutic advantages as agonists and are likely to be devoid of agonist-related problems. These ligands act at a site (allosteric), distinct from the traditional orthosteric site. The allosteric site upon activation induces conformational changes in the orthosteric site which fine-tunes the response of the response of the orthosteric ligands. In most of the cases, allosteric ligands cannot precipitate its action in absence of orthosteric ligands. The fine tuning of receptor helps reduce the dose of the orthosteric ligand which in turn would reduce dose related side effects and also address the receptor de-sensitization issue. In 2007 a HTS lead (AZ-5, GAT236, Figure 4) was reported to act as CB1 positive allosteric modulator (PAM) in the preliminary assays. Since then no further analogs, biochemical or pharmacological studies on this template has been reported. The objective of the present study was to develop newer analogs of this lead by exploration of this scaffold and evaluation of these analogs for their PAM activity. Four sites of variation were identified in the lead carbazole template. For the scope of current study, carbazole ring was kept unaltered and rest of the structure was explored by structure-activity relationship (SAR) studies. A novel synthetic route was developed to ensure rapid synthesis of the compounds with acceptable yields. Fifteen analogs thus synthesized, were tested for the potentiation of EC20 agonist dose in -arrestin and cAMP assays. All the compounds were found to be active selectively in cAMP assay with insignificant potentiation of agonist response -arrestin assay. None of the compounds displayed more PAM activity compared to the original lead molecule. This study is involved in development of novel route for rapid synthesis of GAT236 analogs. The preliminary data obtained from the functional testing of the synthesized molecules has provided useful information for further lead optimization." @default.
• W2768777112 created "2017-12-04" @default.
• W2768777112 creator A5062634634 @default.
• W2768777112 date "2021-05-10" @default.
• W2768777112 modified "2023-09-25" @default.
• W2768777112 title "Design and synthesis of positive allosteric modulators of CB1 cannabinoid receptor" @default.
• W2768777112 doi "https://doi.org/10.17760/d20198049" @default.
• W2768777112 hasPublicationYear "2021" @default.
• W2768777112 type Work @default.
• W2768777112 sameAs 2768777112 @default.
• W2768777112 citedByCount "0" @default.
• W2768777112 crossrefType "dissertation" @default.
• W2768777112 hasAuthorship W2768777112A5062634634 @default.
• W2768777112 hasBestOaLocation W27687771121 @default.
• W2768777112 hasConcept C135285700 @default.
• W2768777112 hasConcept C148001335 @default.
• W2768777112 hasConcept C166342909 @default.
• W2768777112 hasConcept C169760540 @default.
• W2768777112 hasConcept C170493617 @default.
• W2768777112 hasConcept C185592680 @default.
• W2768777112 hasConcept C2776038425 @default.
• W2768777112 hasConcept C2778938600 @default.
• W2768777112 hasConcept C2780871563 @default.
• W2768777112 hasConcept C43587935 @default.
• W2768777112 hasConcept C46721173 @default.
• W2768777112 hasConcept C55493867 @default.
• W2768777112 hasConcept C74187038 @default.
• W2768777112 hasConcept C86803240 @default.
• W2768777112 hasConcept C89951826 @default.
• W2768777112 hasConcept C98274493 @default.
• W2768777112 hasConceptScore W2768777112C135285700 @default.
• W2768777112 hasConceptScore W2768777112C148001335 @default.
• W2768777112 hasConceptScore W2768777112C166342909 @default.
• W2768777112 hasConceptScore W2768777112C169760540 @default.
• W2768777112 hasConceptScore W2768777112C170493617 @default.
• W2768777112 hasConceptScore W2768777112C185592680 @default.
• W2768777112 hasConceptScore W2768777112C2776038425 @default.
• W2768777112 hasConceptScore W2768777112C2778938600 @default.
• W2768777112 hasConceptScore W2768777112C2780871563 @default.
• W2768777112 hasConceptScore W2768777112C43587935 @default.
• W2768777112 hasConceptScore W2768777112C46721173 @default.
• W2768777112 hasConceptScore W2768777112C55493867 @default.
• W2768777112 hasConceptScore W2768777112C74187038 @default.
• W2768777112 hasConceptScore W2768777112C86803240 @default.
• W2768777112 hasConceptScore W2768777112C89951826 @default.
• W2768777112 hasConceptScore W2768777112C98274493 @default.
• W2768777112 hasLocation W27687771121 @default.
• W2768777112 hasOpenAccess W2768777112 @default.
• W2768777112 hasPrimaryLocation W27687771121 @default.
• W2768777112 hasRelatedWork W1573456162 @default.
• W2768777112 hasRelatedWork W2000511535 @default.
• W2768777112 hasRelatedWork W2038956555 @default.
• W2768777112 hasRelatedWork W2336857274 @default.
• W2768777112 hasRelatedWork W2749469617 @default.
• W2768777112 hasRelatedWork W2768777112 @default.
• W2768777112 hasRelatedWork W2973117472 @default.
• W2768777112 hasRelatedWork W2990213332 @default.
• W2768777112 hasRelatedWork W3180744913 @default.
• W2768777112 hasRelatedWork W4290737507 @default.
• W2768777112 isParatext "false" @default.
• W2768777112 isRetracted "false" @default.
• W2768777112 magId "2768777112" @default.
• W2768777112 workType "dissertation" @default.