Synthesis, Structure, and Redox Reactivity of Ni Complexes Bearing a Redox and Acid-Base Non-innocent Ligand with Ni, Ni, and Ni Formal Oxidation States.

A series of Ni complexes bearing a redox and acid-base noninnocent tetraamido macrocyclic ligand, H-(TAML-4) {H-(TAML-4) = 15,15-dimethyl-5,8,13,17-tetrahydro-5,8,13,17-tetraaza-dibenzo[]cyclotridecene-6,7,14,16-tetraone}, with formal oxidation states of Ni, Ni, and Ni were synthesized and characterized structurally and spectroscopically. The X-ray crystallographic analysis of the Ni complexes revealed a square planar geometry, and the [Ni(TAML-4)] complex with the formal oxidation state of Ni was characterized to be [Ni(TAML-4)] with the oxidation state of the Ni ion and the one-electron oxidized TAML-4 ligand, TAML-4. The Ni oxidation state and the TAML-4 radical cation ligand, TAML-4, were supported by X-ray absorption spectroscopy and density functional theory calculations.

A Phase 3, 28-week, multicentre, randomised, double-blind, placebo-controlled trial (OA-10) to evaluate the efficacy and safety of a single injection of lorecivivint in the target knee joint of moderately to severely symptomatic osteoarthritis patients.

Objectives: To assess the efficacy and safety of an intra-articular (IA) CLK/DYRK inhibitor, lorecivivint (LOR), for the treatment of moderate to severe symptomatic knee osteoarthritis (OA).

Methods: This was a Phase 3, 28-week, multicentre, double-blind, placebo-controlled study evaluating the efficacy and safety of a single IA injection of LOR. Patients with ACR-defined knee OA, Kellgren-Lawrence (KL) grades 2-3, and pain Numeric Rating Scale (NRS) ≥4 and ≤8 in the target knee were randomised (1:1) to receive LOR 0.

Phase 3, 56-week, randomised, double-blind, placebo-controlled study utilising patient-reported and radiographic outcomes evaluating the efficacy and safety of a lorecivivint injection in patients with moderate to severe knee osteoarthritis: OA-11 Study.

Objectives: To determine the efficacy, safety, and tolerability of intraarticular (IA) lorecivivint (LOR) in the treatment of knee osteoarthritis (OA).

Methods: Patients with American College of Rheumatology criteria-defined knee OA, Kellgren-Lawrence (KL) grades 2-3, and medial Joint Space Width (JSW) by radiograph between 1.5 and 4 mm in the target knee were enrolled in this phase 3, 56-week, multicentre, double-blind, placebo-controlled study.