In an effort to develop esterase-sensitive pro-prodrugs for amines, an amide derivative of 3-(2'-acetoxy-4',6'-dimethylphenyl)-3,3- dimethylpropionic acid (4-methoxyaniline amide 8) was synthesized and its stability investigated. This esterified hydroxy amide was found under all conditions to degrade via a two-step process initiated by acetyl ester hydrolysis generating the hydroxy amide intermediate 9a. The lactonization of this intermediate 9a in the second step resulted in the formation of 4-methoxyaniline (10) and 4,4,5,7-tetramethyl-3,4-dihydrocoumarin (1a). The pro-prodrug 8 was observed to possess the following half-lives at 37 degrees C under various conditions: 4030 min in phosphate buffer (50 mM, mu = 0.15) fixed to pH 7.4, 11.9 min in the same buffer containing a porcine liver esterase, 53.7 min in plasma, and 475 min in plasma containing diisopropylfluorophosphate. These results suggest that in a biological milieu the ester hydrolysis will occur by the enzymic hydrolysis rather than the chemical hydrolysis and that the enzymic hydrolysis of 8 in plasma is due, in part, to the action of serine-dependent esterases.

When treating seriously ill patients, those working in the healing professions may be particularly vulnerable to their own stress symptoms. Left unattended, these professionals may go down the dark road leading to burnout, with impaired effectiveness as caregivers, diseases rooted in stress, as well as increased suicides, drug and alcohol addiction, and exacerbation of personality disorders. Early intervention may help reduce the associated problems. In this paper, we present an elementary debriefing system, a psychotherapeutic approach, to be used by the affected individual. While this methodology may be far more simplistic than those utilized in different schools of healing or caregiving, its appeal is its simplicity and practicality. We are proposing that the individual caregiver systematically consider the following: the Background of the situation; how it Affects thinking and feeling; the Troublesome element(s); how one is Handling element(s); and an Empathetic/empowering conclusion (BATHE). Ideally, these considerations may help alleviate caregivers' anguish in troublesome situations and may complement their awareness of their patients' suffering as well.