Evaluation of a non-prime site substituent and warheads combined with a decahydroisoquinolin scaffold as a SARS 3CL protease inhibitor.

A non-prime site substituent and warheads combined with a decahydroisoquinolin scaffold was evaluated as a novel inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CLpro). The decahydroisoquinolin scaffold has been demonstrated to be an effective hydrophobic center to interact with S2 site of SARS 3CLpro, but the lack of interactions at S3 to S4 site is thought to be a major reason for the moderate inhibitory activity. In this study, the effects of an additional non-prime site substituent on the scaffold as well as effects of several warheads are evaluated. For the introduction of a desired non-prime site substituent, amino functionality was introduced on the decahydroisoquinolin scaffold, and the scaffold was constructed by Pd(II) catalyzed diastereoselective ring formation. The synthesized decahydroisoquinolin inhibitors showed about 2.4 times potent inhibitory activities for SARS 3CLpro when combined with a non-prime site substituent. The present results indicated not only the expected additional interactions with the SARS 3CLpro but also the possibility of new inhibitors containing a fused-ring system as a hydrophobic scaffold and a new warhead such as thioacetal.

[Survey of ocular injury by solar eclipse 2009].

PURPOSE: Incidence of ocular injury caused by the solar eclipse of 2009 has been investigated using the questionnaire of the Japan Committee of the International Year of Astronomy 2009. METHODS: The questionnaire was available to the public on the website. RESULTS: Answers were obtained from 14 people (12 men, 2 women), aged from sixteen to fifty-four. All had looked at the sun either with the naked eye or through some shading device (plastic sheet, plastic bag, compact disc, etc.) the safty of which is unknown. Reported symptoms included a sense of incongruity, heat, pain, central scotoma or visual disturbance, classified into four periods of duration. Three people with transient symptoms watched the eclipse with the naked eye for one minute in cloudy weather. Three people with symptoms lasting for one day and three people with symptoms lasting for one week had watched it with the naked eye and some shading device for 10 minutes in cloudy weather. Five people with symptoms lasting for more than one week watched the eclipse with the naked eye and through some sort of device in fine or slightly cloudy weather. Three people consulted their ophthalmologist. CONCLUSIONS: Those who reported adverse symptoms did not comply with the instructions for safe watching of the eclipse and the duration of the symptoms depended on the weather and the type of device used.