Structure-guided design of α-amino acid-derived Pin1 inhibitors

Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds

“…168 They used inhibitors 56 and 65a to saturate the binding site, followed by screening of approximately 1200 fragments in displacement assays. From the screen, the most potent active was an indole-2-carboxylic acid ( 75 ) with an IC 50 ≈ 16 μ M. The crystal structure of 75 bound to Pin1 showed that the indole contacts the bottom of the proline-binding site.…”

Prolyl Isomerase Pin1 Negatively Regulates AMP-activated Protein Kinase (AMPK) by Associating with the CBS Domain in the γ Subunit

“…Thus, we employed not only Juglone but also two other Pin1 inhibitor types possibly more highly specific for Pin1, both of which were custom-made by SundiaMediTech Company Ltd. (Shanghai, China). The one termed Pin1 inhibitor 1 is (R)-2-(5-(4-methoxyphenyl)-2-methylfuran-3-caroxamido)-3-(naphthalen-6-yl) propanoic acid (32), and the other, termed Pin1 inhibitor 2, is 4-(N-benzyl- (33). These inhibitors were added to cells 30 min prior to 2-deoxyglucose (2-DG) treatment.…”

Palladium-Catalyzed Regioselective 2-Carbethoxyethylation of 1H– Indoles By C-H Activation: One-Step Synthesis of Ethyl 2-(1H-Indol-2-Yl) Acetates

“…Given the possibility that excessive water in the solvent might hydrolyse the arylpalladium(II) species formed in the first oxidative addition step and lower the solubility of the intermediates, resulting in a cessation of the catalytic cycle and undesired conversion rate, we switched the solvent back to DMF with 0.5M H 2 O. Finally, a brief screen of bases showed an interesting correlation between the alkalinity of the base and the yield of the 2,3-disubstitued-indole byproduct 2 ( Table 1, [11][12][13][14][15]. Specifically, the yields of the 2,3-disubstitued-indole products increased significantly as the alkalinity of the base increased, with NaHCO 3 affording the target products in desirable yields.…”

“…Among them, 2-(1H-indol-2-yl)acetic acids constitute a valuable class of building blocks for natural product and natural product analogue syntheses ( Figure 1) [4][5][6][7], combinatorial [8], diversity-oriented syntheses [9,10], and medicinal chemistry [11][12][13][14][15][16][17][18]. In addition, they can serve as highly attractive precursors for various chemical transformations, such as diazomethylation to 1-diazo-3-(2-indolyl)-2-propanone [19] and reduction to 2-(2-hydroxyethyl) indole [20].…”