Neumann, William L. published the artcileSynthesis and structure-activity relationships of 3,4,5-trisubstituted-1,2,4-triazoles: high affinity and selective somatostatin receptor-4 agonists for Alzheimer′s disease treatment, SDS of cas: 104-01-8, the main research area is somatostatin receptor agonist triazole SAR affinity Alzheimer disease treatment.
Somatostatin receptor-4 (SST4) is highly expressed in brain regions affiliated with learning and memory. SST4 agonist treatment may act to mitigate Alzheimer′s disease (AD) pathol. An integrated approach to SST4 agonist lead optimization is presented herein. High affinity and selective agonists with biol. efficacy were identified through iterative cycles of a structure-based design strategy encompassing computational methods, chem., and preclin. pharmacol. 1,2,4-Triazole derivatives of our previously reported hit (4) showed enhanced SST4 binding affinity, activity, and selectivity. Thirty-five compounds showed low nanomolar range SST4 binding affinity, 12 having a Ki < 1 nM. These compounds showed >500-fold affinity for SST4 as compared to SST2A. SST4 activities were consistent with the resp. SST4 binding affinities (EC50 < 10 nM for 34 compounds). Compound 208 (SST4Ki = 0.7 nM; EC50 = 2.5 nM; >600-fold selectivity over SST2A) display a favorable physiochem. profile, and was advanced to learning and memory behavior evaluations in the senescence accelerated mouse-prone 8 model of AD-related cognitive decline. Chronic administration enhanced learning with i.p. dosing (1 mg kg-1) compared to vehicle. Chronic administration enhanced memory with both i.p. (0.01, 0.1, 1 mg kg-1) and oral (0.01, 10 mg kg-1) dosing compared to vehicle. This study identified a novel series of SST4 agonists with high affinity, selectivity, and biol. activity that may be useful in the treatment of AD.
RSC Medicinal Chemistry published new progress about Affinity (binding). 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, SDS of cas: 104-01-8.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem