2-Pyridyl P1'-substituted symmetry-based human immunodeficiency virus protease inhibitors (A-792611 and A-790742) with potential for convenient dosing and reduced side effects.

A series of symmetry-based HIV protease inhibitors was designed and synthesized. Modification of the core regiochemistry and stereochemistry significantly affected the potency, metabolic stability, and oral bioavailability of the inhibitors, as did the variation of a pendent arylmethyl P3 group. Optimization led to the selection of two compounds, 10c (A-790742) and 9d (A-792611), for advancement to preclinical studies.

An evaluation of 3,4-methylenedioxy phenyl replacements in the aminopiperidine chromone class of MCHr1 antagonists.

The optimization of potent MCHr1 antagonist 1 with respect to improving its in vitro profile by replacement of the 3,4-methylenedioxy phenyl (piperonyl) moiety led to the discovery of 19, a compound that showed excellent MCHr1 binding and functional potencies in addition to possessing superior hERG separation, CYP3A4 profile, and receptor cross-reactivity profiles.

Antidiabetic activity of passive nonsteroidal glucocorticoid receptor modulators.

Much has been learned about the consequences of glucocorticoid receptor antagonism by studying steroidal active antagonists such as RU-38486 (1). In the liver glucocorticoid receptor antagonism suppresses hepatic glucose production decreasing plasma glucose levels; however, extrahepatic antagonism produces several undesirable side effects including activation of the hypothalamic pituitary adrenal axis. A series of nonsteroidal passive N-(3-dibenzylamino-2-alkyl-phenyl)-methanesulfonamide glucocorticoid receptor modulators was discovered.

Development of potentially better practices for the neonatal intensive care unit as a culture of collaboration: communication, accountability, respect, and empowerment.

Objective: The Vermont Oxford Network (VON) CARE Group was formed in response to the need to create organizational cultures supportive of change and quality improvement.

Methods: The CARE Group consisted of team members from 4 participating neonatal intensive care units (NICUs). All CARE Group members chose to work on multidisciplinary teamwork for the duration of the Neonatal Intensive Care Quality Improvement Collaborative Year 2000.

Factors affecting the delivery of HIV/AIDS prevention programs by community-based organizations.

Community based organizations (CBOs) play a frontline role in HIV/AIDS prevention activities. CBOs face formidable challenges to effective delivery of HIV prevention services including client characteristics such as homelessness and CBO characteristics such as limited resources and staff turnover. Despite these obstacles, CBOs are generally well positioned to deliver services to specific high-risk populations because they understand their local communities and are connected to the groups they serve.