Spirocyclic nitriles as protease inhibitors

Abstract

The invention relates to substituted carbo- and heterocyclic spiro compounds of the formula Ia which inhibit thiol proteases, to processes for their preparation and to the use thereof as medicaments.

What is claimed is: 
     
         1 . A compound selected from the group consisting of:
 N—[(S)-1-(1-cyanocyclopropylcarbamoyl)-3-methylbutyl]-1,4-dioxaspiro[4.5]decane-8-carboxamide;   N-[1-(1-cyanocyclopropylcarbamoyl)cyclohexyl]-8-azaspiro[4.5]decane-8-carboxamide;   N—[(S)-1-(1-cyanocyclopropylcarbamoyl)-cyclohexylmethyl-8-azaspiro[4.5]decane-8-carboxamide;   N—[(S)-1-(1-cyanocyclopropylcarbamoyl)-3-methylbutyl]spiro[2.3]hexane-1-carboxamide;   
       or a physiologically tolerated salt thereof. 
     
     
         2 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 1  or a physiologically tolerated salt thereof and a pharmaceutically acceptable carrier. 
     
     
         3 . A method of treating a disease, condition or disorder selected from abnormally elevated bone degradation, allergies, Alzheimer's disease, amyloidosis, ARDS, arterial thrombosis, asthma, atheromas, atherosclerosis, autoimmune disorders, bacterial infections, bronchiolitis, cerebral hemorrhage, cerebrovascular ischemia, Huntington's chorea, chronic inflammations, CIPD (chronic inflammatory demyelinizing polyradiculoneuropathy), Creutzfeldt-Jakob disease, Crohn's disease, diabetes, emphysema, encephalomyelitis, endometriosis, inflammatory respiratory disorders, inflammatory pancreatitis, epilepsy, disorders characterized by enhanced angiogenesis, excessive respiratory pathway elastolysis, tissue grafts, gingivitis, glomerulonephritis, glucocorticoid-induced osteoporosis, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, hepatitis, HIV infection, Huntington's disease, hypercalcemia, IBD, immune impairment, interstitial cystitis, bone fracture, bone loss, cancers, lupus erythematosus, malaria, metachromic leukodystrophy, metastasizing osteogenesis, metastatis, multiple sclerosis, multiple myeloma, muscular dystrophy, myasthenia gravis, neurodegenerative disorders, neuropathic pain, chronic or diabetic neuropathy, post-therapeutic neuralgia, trigeminal neuralgia, painful diabetic polyneuropathy, post-stroke pain, post-amputation pain, myelopathic or radiculopathic pain, atypical facial pain and causalgia-like syndromes, organ rejection in transplants, osteoarthritis, osteogenesis imperfecta, osteoporosis, Paget's disease, pancreatitis, Parkinson's disease, pemphigus vulgaris, periodontitis, plaque rupture,  Pneumocystis carinii , pneumonitis, psoriasis, restenosis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, brain trauma, spinal cord trauma, tumor cell invasion, viral infections, tooth loss, breast cancer, intestinal cancer, ovarian cancer, cervical cancer, skin cancer, brain tumor, Kaposi's sarcoma, B- and T-cell leukemia, lung cancer, lymph node cancer, pancreatic cancer, prostrate cancer and sarcomas; 
       said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to  claim 1  or a physiologically tolerated salt thereof. 
     
     
         4 . The method of  claim 3 , wherein the condition or disorder is osteoarthritis. 
     
     
         5 . The method of  claim 3 , wherein the condition or disorder is bone loss.