Evaluation of (4-Arylpiperidin-1-yl)cyclopentanecarboxamides as high-affinity and long-residence-time antagonists for the CCR2 receptor was written by Vilums, Maris;Zweemer, Annelien J. M.;Dilanchian, Arian;van Veldhoven, Jacobus P. D.;de Vries, Henk;Brussee, Johannes;Saunders, John;Stamos, Dean;Heitman, Laura H.;IJzerman, Adriaan P.. And the article was included in ChemMedChem in 2015.Computed Properties of C10H11ClF3N This article mentions the following:
Animal models suggest that the chemokine ligand 2/CC-chemokine receptor 2 (CCL2/CCR2) axis plays an important role in the development of inflammatory diseases. However, CCR2 antagonists have failed in clin. trials because of a lack of efficacy. We previously described a new approach for the design of CCR2 antagonists by the use of structure-kinetics relationships (SKRs). Herein we report new findings on the structure-affinity relationships (SARs) and SKRs of the reference compound MK-0483, its diastereomers, and its structural analogs as CCR2 antagonists. The SARs of the 4-arylpiperidine group suggest that lipophilic hydrogen-bond-accepting substituents at the 3-position are favorable. However, the SKRs suggest that a lipophilic group with a certain size is desired [e.g., 3-Br: Ki=2.8 nΜ, residence time (tres)=243 min; 3-iPr: Ki=3.6 nΜ, tres=266 min]. Alternatively, addnl. substituents and further optimization of the mol., while keeping a carboxylic acid at the 3-position, can also prolong tres; this was most prominently observed in MK-0483 (Ki=1.2 nΜ, tres=724 min) and a close analog (Ki=7.8 nΜ) with a short residence time. In the experiment, the researchers used many compounds, for example, 7-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 220247-87-0Computed Properties of C10H11ClF3N).
7-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 220247-87-0) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline motif is often present in natural products with a broad range of biological and pharmacological activities. Among them, 1-substituted tetrahydroisoquinolines are privileged scaffolds in drugs and pharmaceuticals. Arene/Ru/TsDPEN complexes bearing a heterocyclic group catalyze the asymmetric transfer hydrogenation (ATH) of 1-aryl dihydroisoquinolines (DHIQs) to provide tetrahydroisoquinolines of high enantiomeric excess.Computed Properties of C10H11ClF3N
Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem