The serine protease tryptase has been implicated in allergic and inflammatory diseases and associated with asthma. The synthesis and SAR of a series of N1-activated-4-carboxy azetidinones are described, resulting in identification of BMS-363131 (2) as a potent inhibitor of human tryptase (IC(50)<1.7 nM) with high selectivity (>3000-fold) for tryptase versus related serine proteases including trypsin.

A recently proposed method for solving the one-particle generalized Smoluchowski equation is used to determine the light scattering spectrum for a dilute solution of spherical, uncharged macromolecules. We find a frequency and wave number dependent effective diffusion coefficient which offers a possible explanation for the difference in sign found for this quantity at small and large frequencies in previous work. Our results are based on the use of Oseen's model for the hydrodynamic interaction, and in this sense are considered as preliminary; an extension of these results using a higher order hydrodynamic theory is in progress.

We use an improved version of the solution to the one particle generalized Smoluchowski equation found earlier to calculate the self-diffusion coefficient D and the long time behavior of the momentum autocorrelation function φ (t) for a dilute system of uncharged, spherical macromolecules in solution. For D we find the infinite dilution result which is consistent with other theories based on Oseen’s model which we also use; our calculation does eliminate some other assumptions which are used in previous calculations. The asymptotic decay of φ (t) is found to be algebraic, as t−5/2; the −5/2 exponent is probably due to the use of Oseen’s model, and for a higher order hydrodynamic theory which gives a nonvanishing o (c) contribution to D we expect that φ (t) will decay as t−3/2.