Psychiatric Comorbidity and Complications.

This article highlights the prevalence of co-occurring disorders among adolescents and underscores the complexity and opportunities of treating these patients in a systematic, comprehensive approach. As evidenced by this review, the need exists to develop and test models of care that integrate co-occurring disorders into both psychiatric and substance abuse treatment settings. The challenge for pediatric practitioners is to provide detailed assessments linked to evidence-based treatment plans to account for the variations in adolescent development and the unique risk factor profile of each patient. The issues related to co-morbidity are vast and continue to grow with rapidly increasing research literature.

Child Obesity and Mental Health: A Complex Interaction.

Prevalence rates of childhood obesity have risen steeply over the last 3 decades. Given the increased national focus, the frequency of this clinical problem, and the multiple mental health factors that coexist with it, make obesity a public health concern. The complex relationships between mental health and obesity serve to potentiate the severity and interdependency of each. The purpose of this review is to create a contextual connection for the 2 conditions as outlined by the research literature and consider treatment options that affect both health problems.

Synthesis and activity of tryptophan sulfonamide derivatives as novel non-hydroxamate TNF-alpha converting enzyme (TACE) inhibitors.

A novel series of non-hydroxamate tryptophan sulfonamide derivatives containing a butynyloxy P1' moiety was identified as inhibitors of TNF-alpha converting enzyme (TACE). The structure-activity relationship of the series was examined via substitution on the tryptophan indole ring. Of the compounds investigated, 2-(4-(but-2-ynyloxy)phenylsulfonamido)-3-(1-(4-methoxybenzyl)-1H-indol-3-yl)propanoic acid (12p) has the best in vitro potency against isolated TACE enzyme with an IC(50) of 80 nM. Compound 12p also shows good selectivity over MMP-1, -13, -14.

Design and synthesis of butynyloxyphenyl beta-sulfone piperidine hydroxamates as TACE inhibitors.

A series of butynyloxyphenyl beta-sulfone piperidine hydroxamate TACE inhibitors was designed and synthesized. The resulting structure-activity relationship and MMP selectivity of the series were examined. Of the compounds investigated, 17s has excellent in vitro potency against isolated TACE enzyme, shows good selectivity over MMP-1, -2, -7, -8, -9, -13, and -14, and oral activity in an in vivo mouse model of TNF-alpha production.

Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase.

A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran scaffolds were designed and synthesized. Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubstitution pattern is preferred for the aromatic region. Analog 19 displayed potent activity with an IC(50) of 50 nM against HCV NS5B enzyme and was selective over a panel of polymerases.