Humanizing folk devils using ethnography.

The sociological concepts of the "moral panic" and the deviant "folk devil" apply to the drug panics in the United States over methamphetamine, heroin, and crack cocaine. Mothers or pregnant women who smoke crack cocaine, and their babies, are assigned exaggerated "demonic" attributes that result in stigma and societal rejection. Otherwise, ethnographic studies of drug users demonstrate realities that are other than what might be considered were one to merely look at their use and the consequences. These considerations are examined with respect to the image of folk devils, methadone program attendees, smokers of "blunts," opium den habitués, and others grouped together as negative influences as a result of their drug habits.

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.