2,5-Disubstituted pyridines as potent GPR119 agonists

Searching for novel ligands for the cannabinoid and related receptors.

“…The clustering analysis of propan-2-yl 4-( [6-[4-(propane-1-sulfonyl)piperzin-1-yl]-oxy)methylpiperidine-1-carboxylate (Wu Compound 19A) resulted in the generation of three clusters (Cluster 36, Cluster 64, and Cluster 435) of which a representative fragment from each group is shown which are responsible for the activity of this compound ( Figure 5.3). The fragment analysis indicates that the sulfonamide and carbamate groups are important for Wu Compound 19A agonist activity, which is consistent with previously reported SAR of this compound (Wu et al, 2010).…”

“…The 31 inactive compounds consisted of compounds which do act as agonists for GPR119 at concentrations up to 10 µM, which were experimentally confirmed using the established HTRF assay Recently, Wu et al 2010 synthesized a series of piperazinylpyridine derivatives as GPR119 agonists (Wu et al, 2010). Through SAR analysis, compounds with alkylsulfonamide and isopropylcarbamate end groups displayed potent GPR119 receptor activity (Wu et al, 2010). The clustering analysis of propan-2-yl 4-( [6-[4-(propane-1-sulfonyl)piperzin-1-yl]-oxy)methylpiperidine-1-carboxylate (Wu Compound 19A) resulted in the generation of three clusters (Cluster 36, Cluster 64, and Cluster 435) of which a representative fragment from each group is shown which are responsible for the activity of this compound ( Figure 5.3).…”

“…These 14 known GPR119 agonists were selected from patents and literature sources. The 31 inactive compounds consisted of compounds which do act as agonists for GPR119 at concentrations up to 10 µM, which were experimentally confirmed using the established HTRF assay Recently, Wu et al 2010 synthesized a series of piperazinylpyridine derivatives as GPR119 agonists (Wu et al, 2010). Through SAR analysis, compounds with alkylsulfonamide and isopropylcarbamate end groups displayed potent GPR119 receptor activity (Wu et al, 2010).…”

Chapter 7. Recent Advances in the Discovery of GPR119 Agonists

“…These analogs offered no significant improvement in FaSSIF solubility (3.4 mg/mL for 36), however, and the exposure of 36 after oral administration was low in preclinical species. 75,76 7.4.5 Merck and Co.…”

Synthesis and Herbicidal Activity of 6-Alkoxy(aryloxy) Multisubstituted Pyridine Derivatives

“…近期研究还发现该类化 合物可作为潜在的 GPR119 拮抗剂及消炎药物 [11,12] . 我们课题组开展了对多取代吡啶化合物的研究工作 [13,14] , 并设计合成了一系列含烷氨基或烷硫基的多 取代吡啶衍生物.本文以 6-烷硫基吡啶化合物为原料, Table 1 Herbicidal activity of title compounds (relative inhibition rate%)…”