The present application describes modulators of MIP-1.alpha. of formula (I): ##STR00001## or stereoisomers or pharmaceutically acceptable salts thereof, wherein m, T, W, R.sub.1, R.sub.4, R.sub.5, R.sub.5a and R.sub.5b are as defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using said modulators are disclosed.

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 relates to compounds having the formula, ##STR00001## and pharmaceutically-acceptable salts, prodrugs, solvates, isomers, and/or hydrates thereof, wherein Q is an optionally-substituted phenyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl ring; R.sub.2 is alkyl or an amino group as defined herein; and Z is optionally-substituted oxadiazolyl or --C(.dbd.O)NR.sub.6, wherein R.sub.6 is lower alkyl or cyclopropyl. The compounds are surprisingly advantageous in preparing pharmaceutical compositions for treating p38 kinase related conditions and/or in methods of treating conditions associated with the activity of p38 kinase in a patient.