Design, Synthesis, and Pharmacological Evaluation of Second Generation Soluble Adenylyl Cyclase sAC, ADCY10 Inhibitors with Slow Dissociation Rates

Soluble adenylyl cyclase sAC ADCY10 is an enzyme involved in intracellular signaling. Inhibition of sAC has potential therapeutic utility in a number of areas. For example, sAC is integral to successful male fertility sAC activation is required for sperm motility and ability to undergo the acrosome reaction, two processes central to oocyte fertilization. Pharmacologic evaluation of existing sAC inhibitors for utility as on demand, nonhormonal male contraceptives suggested that both high intrinsic potency, fast on and slow dissociation rates are essential design elements for successful male contraceptive applications. During the course of the medicinal chemistry campaign described here, we identified sAC inhibitors that fulfill these criteria and are suitable for in vivo evaluation of diverse sAC pharmacolog

New developments in small molecular compounds for anti-hepatitis C virus (HCV) therapy*

Infection with hepatitis C virus (HCV) affects approximately 170 million people worldwide. However, no vaccine or immunoglobulin is currently available for the prevention of HCV infection. The standard of care (SOC) involving pegylated interferon-α (PEG-IFN α) plus ribavirin (RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1, the most prevalent type of HCV in North America and Europe. Recently, reliable in vitro culture systems have been developed for accelerating antiviral therapy research, and many new specifically targeted antiviral therapies for hepatitis C (STAT-C) and treatment strategies are being evaluated in clinical trials. These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration. The aim of this review is to summarize the current developments in new anti-HCV drugs