An enzymatic ammonolysis process is provided for the preparation of intermediates used in preparing dipeptidyl peptidase IV inhibitors wherein the enzyme Candida antarctica lipase-B is used to catalyze the ammonolysis process.

There is provided a series of substituted acyl guanidines of Formula (I) ##STR00001## or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 as defined herein, their pharmaceutical compositions and methods of use. These compounds inhibit the processing of amyloid precursor protein (APP) by .beta.-secretase and, more specifically, inhibit the production of A.beta.-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to .beta.-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

In vitro cell-based methods for identifying compounds that inhibit Notch cleavage and methods for identifying .gamma.-secretase inhibitors that exhibit reduced induction of goblet cell metaplasia are provided. Also provided are methods of identifying compounds that inhibit cleavage of .gamma.-secretase substrates other than Notch and homogeneous compositions or cultures of Notch-expressing cells that undergo mucin-2 or mucin-5AC induction in response to a compound known to inhibit Notch cleavage and methods of their generation.

The present invention provides compounds of formula I ##STR00001## and pharmaceutically acceptable salts thereof.The formula I compounds inhibit tyrosine kinase activity of Trk receptors such as TrkA, TrkB and TrkC thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.

Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-.kappa.B activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) ##STR00001## or stereoisomers or prodrugs or solvates or pharmaceutically acceptable salts thereof, wherein A, B, J, K, Z, R, R.sup.a, R.sup.b, R.sup.c, and R.sup.d, are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.