The present invention relates in part to a process for the preparation of a proline derivative of formula I ##STR00001## wherein, R.sup.1 is C.sub.1-7-alkyl or ##STR00002## wherein R.sup.4 is selected from the group consisting of C.sub.1-7-alkyl, halogen-C.sub.1-7-alkyl and phenyl optionally substituted by halogen; R.sup.2 is halogen or halogen-C.sub.1-7-alkyl; and R.sup.3 is selected from the group consisting of hydrogen, halogen, halogen-C.sub.1-7-alkyl, C.sub.1-7-alkoxy, halogen-C.sub.1-7-alkoxy and a 5- or 6-membered heterocyclic ring containing one or two nitrogen atoms, said ring being optionally substituted by C.sub.1-7-alkyl or halogen. The proline derivatives of the formula I are preferential inhibitors of the cysteine protease Cathepsin S and are therefore useful to treat metabolic diseases like diabetes, atherosclerosis, abdominal aortic aneurysm, peripheral arterial disease and diabetic nephropathy.

Hoffmann-La Roche Inc.

Process for the preparation of proline derivatives

The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.

Brigham &amp; Women's Hospital

S-nitroso derivatives of hydrazinoacetic acids, 1-[(acylthio and (mercapto)-1-oxoalkyl]-1,2,34-Tetrahydroquinoline-2-carboxylic acids and alanyl prolines and isoquinolines

diabetic nephropathies/proline

Process for the preparation of proline derivatives

S-nitroso derivatives of hydrazinoacetic acids, 1-[(acylthio and (mercapto)-1-oxoalkyl]-1,2,34-Tetrahydroquinoline-2-carboxylic acids and alanyl prolines and isoquinolines

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