Cluster Analysis and Discriminant Analysis for Determining Post-Earthquake Road Recovery Patterns.

The transport network in eastern Japan was severely damaged by the 2011 Tohoku earthquake. To understand the road recovery conditions after a large earthquake, a large amount of time is needed to collect information on the extent of the damage and road usage. In our previous study, we applied cluster analysis to analyze the data on driving vehicles in Fukushima prefecture to classify the road recovery conditions among municipalities within the first six months after the earthquake. However, the results of the cluster analysis and relevant factors affecting road recovery from that study were not validated. In this study, we proposed a framework for determining post-earthquake road recovery patterns and validated the cluster analysis results by using discriminant analysis and observing them on a map to identify their common characteristics. In addition, our analysis of objective data reflecting regional characteristics showed that the road recovery conditions were similar according to the topography and the importance of roads.

Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series.

SAR studies were conducted around lead compound 1 using high-throughput parallel solution and solid phase synthesis. Our lead optimization efforts led to the identification of several CCR2b antagonists with potent activity in both binding and functional assays [Compound 71 CCR2b Binding IC(50) 3.2 nM; MCP-1-Induced Chemotaxis IC(50) 0.83 nM; Ca(2+) Flux IC(50) 7.5 nM].

Small molecule inhibitors of the CCR2b receptor. Part 1: Discovery and optimization of homopiperazine derivatives.

N,N'-Disubstituted homopiperazine derivatives have been discovered as CC-chemokine receptor 2b (CCR2b) inhibitors with submicromolar activity in the CCR2b binding assay. A 4-substituted benzyl group on one homopiperazine nitrogen was an important moiety for binding affinity to the CCR2b receptor. The SAR for CCR2b binding affinity correlated inversely with the sigma factor of the functional group on this benzyl moiety. Introduction of hydroxy groups to appropriate positions in the 3,3-diphenylpropyl group on the other homopiperazine nitrogen increased CCR2b binding activity. The synthesis of an informer library to search for alternative substructures is also described.

Small molecule antagonists of the CCR2b receptor. Part 2: Discovery process and initial structure-activity relationships of diamine derivatives.

Structure-activity relationships (SAR) of a weakly active class of CCR2b inhibitors were utilized to initiate a lead evolution program employing the Drug Discovery Engine. Several alternative structural series have been discovered that display nanomolar activity in the CCR2b binding and CCR2b-mediated chemotaxis assays.