CARDIO VASCULAR DIABETOLOGY ORIGINAL INVESTIGATION Open Access

Novel fusion of GLP-1 with a domain antibody to serum albumin prolongs protection against myocardial ischemia/reperfusion injury in the ra

4,6-Diaminopyrimidines as Highly Preferred Troponin I‑Interacting Kinase (TNNI3K) Inhibitors

Structure-guided progression of a purine-derived series of TNNI3K inhibitors directed design efforts that produced a novel series of 4,6-diaminopyrimidine inhibitors, an emerging kinase binding motif. Herein, we report a detailed understanding of the intrinsic conformational preferences of the scaffold, which impart high specificity for TNNI3K. Further manipulation of the template based on the conformational analysis and additional structure–activity relationship studies provided enhancements in kinase selectivity and pharmacokinetics that furnished an advanced series of potent inhibitors. The optimized compounds (e.g., GSK854) are suitable leads for identifying new cardiac medicines and have been employed as <i>in vivo</i> tools in investigational studies aimed at defining the role of TNNI3K within heart failure

4,6-Diaminopyrimidines as Highly Preferred Troponin I‑Interacting Kinase (TNNI3K) Inhibitors

Structure-guided progression of a purine-derived series of TNNI3K inhibitors directed design efforts that produced a novel series of 4,6-diaminopyrimidine inhibitors, an emerging kinase binding motif. Herein, we report a detailed understanding of the intrinsic conformational preferences of the scaffold, which impart high specificity for TNNI3K. Further manipulation of the template based on the conformational analysis and additional structure–activity relationship studies provided enhancements in kinase selectivity and pharmacokinetics that furnished an advanced series of potent inhibitors. The optimized compounds (e.g., GSK854) are suitable leads for identifying new cardiac medicines and have been employed as <i>in vivo</i> tools in investigational studies aimed at defining the role of TNNI3K within heart failure

4,6-Diaminopyrimidines as Highly Preferred Troponin I‑Interacting Kinase (TNNI3K) Inhibitors

Structure-guided progression of a purine-derived series of TNNI3K inhibitors directed design efforts that produced a novel series of 4,6-diaminopyrimidine inhibitors, an emerging kinase binding motif. Herein, we report a detailed understanding of the intrinsic conformational preferences of the scaffold, which impart high specificity for TNNI3K. Further manipulation of the template based on the conformational analysis and additional structure–activity relationship studies provided enhancements in kinase selectivity and pharmacokinetics that furnished an advanced series of potent inhibitors. The optimized compounds (e.g., GSK854) are suitable leads for identifying new cardiac medicines and have been employed as <i>in vivo</i> tools in investigational studies aimed at defining the role of TNNI3K within heart failure

4,6-Diaminopyrimidines as Highly Preferred Troponin I‑Interacting Kinase (TNNI3K) Inhibitors

Structure-guided progression of a purine-derived series of TNNI3K inhibitors directed design efforts that produced a novel series of 4,6-diaminopyrimidine inhibitors, an emerging kinase binding motif. Herein, we report a detailed understanding of the intrinsic conformational preferences of the scaffold, which impart high specificity for TNNI3K. Further manipulation of the template based on the conformational analysis and additional structure–activity relationship studies provided enhancements in kinase selectivity and pharmacokinetics that furnished an advanced series of potent inhibitors. The optimized compounds (e.g., GSK854) are suitable leads for identifying new cardiac medicines and have been employed as <i>in vivo</i> tools in investigational studies aimed at defining the role of TNNI3K within heart failure

4,6-Diaminopyrimidines as Highly Preferred Troponin I‑Interacting Kinase (TNNI3K) Inhibitors

Structure-guided progression of a purine-derived series of TNNI3K inhibitors directed design efforts that produced a novel series of 4,6-diaminopyrimidine inhibitors, an emerging kinase binding motif. Herein, we report a detailed understanding of the intrinsic conformational preferences of the scaffold, which impart high specificity for TNNI3K. Further manipulation of the template based on the conformational analysis and additional structure–activity relationship studies provided enhancements in kinase selectivity and pharmacokinetics that furnished an advanced series of potent inhibitors. The optimized compounds (e.g., GSK854) are suitable leads for identifying new cardiac medicines and have been employed as <i>in vivo</i> tools in investigational studies aimed at defining the role of TNNI3K within heart failure

4,6-Diaminopyrimidines as Highly Preferred Troponin I‑Interacting Kinase (TNNI3K) Inhibitors

Structure-guided progression of a purine-derived series of TNNI3K inhibitors directed design efforts that produced a novel series of 4,6-diaminopyrimidine inhibitors, an emerging kinase binding motif. Herein, we report a detailed understanding of the intrinsic conformational preferences of the scaffold, which impart high specificity for TNNI3K. Further manipulation of the template based on the conformational analysis and additional structure–activity relationship studies provided enhancements in kinase selectivity and pharmacokinetics that furnished an advanced series of potent inhibitors. The optimized compounds (e.g., GSK854) are suitable leads for identifying new cardiac medicines and have been employed as <i>in vivo</i> tools in investigational studies aimed at defining the role of TNNI3K within heart failure