The invention provides derivatives of kallikrein-trypsin inhibitor (BPTI) in which one or both of the 10- or 21-tyrosine residues are linked, in the o-position relative to the phenolic hydroxyl group, to an aptionally substituted carbocyclic or heterocyclic aromatic radical via an azo group and the other if only one of the said residues is substituted is either unsubstituted or carries a nitro group or an amino group in the o-position relative to the phenolic hydroxyl group.The azo-BPTI derivatives of the invention can be used, as medicaments for the therapy of diseases which are caused either by over-production of proteases as a result of increased liberation from the zymogens or of release during cell decomposition or by a deficiency or lack of natural indogenous inhibitors of these enzymes in organs and tissue fluids. Diseases which have this type of etiology are the various forms of shock and post-traumatic or post-operative complications, disorders in blood clotting and acute and chronic inflammatory reactions and, in particular, also chronic inflammatory reactions with necrotic and degenerative damage to connective tissue, such as pancreatitis and also vasculitides, glomerulonephritides, rheumatoid arthritis and other collagenoses caused by immune complexes and also arthritides caused by deposits due to metabolic processes (gout), but also degenerative changes in the elastic elements of vascular walls (arterioscleroses) or in the lung (pulmonary emphysema).

Bayer Aktiengesellschaft

Derivatives, having an inhibitory action against protease and an antiphlogistic action, of the trypsin-kallikrein inhibitor obtained from cattle organs (BPTI), their preparation and their use as medicaments

Compounds of the formula I ##STR00001## wherein R.sup.1a is H; and R.sup.1b is C.sub.1-C.sub.6 alkyl, Carbocyclyl or Het; or R.sup.1a and R.sup.1b together define a saturated cyclic amine with 3-6 ring atoms; R.sup.2a and R.sup.2b are H, halo, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy; or R.sup.2a and R.sup.2b together with the carbon atom to which they are attached form a C.sub.3-C.sub.6cycloalkyl; R.sup.3 is a branched C.sub.5-C.sub.10alkyl chain, C.sub.2-C.sub.4haloalkyl or C.sub.3-C.sub.7cycloalkylmethyl, R.sup.4 is Het, Carbocyclyl, optionally substituted as defined in the specification and pharmaceutically acceptable salts, hydrates and N-oxides thereof; are inhibitors of cathepsin S and have utility in the treatment of psoriasis, autoimmune disorders and other disorders such as asthma, arteriosclerosis, COPD and chronic pain.

Ayesa; Susana

Belfrage; Anna Karin

Classon; Bjorn

Grabowska; Urszula

Hewitt; Ellen

Ivanov; Vladimir

Jonsson; Daniel

Kahnberg; Pia

Lind; Peter

Nilsson; Magnus

Oden; Lourdes

Pelcman; Mikael

Wahling; Horst

Medivir UK Ltd

Cysteine protease inhibitors

The invention refers to multibasic, N-terminally modified tetrapeptide mimetics with a C-terminal P1-arginine mimetic, methods for their production and use for therapy and prophylaxis of diseases, caused by bacterial pathogens or viruses, as well as for therapy and prophylaxis of diabetes, arteriosclerosis, cancer, Alzheimer's or the onset of obesity, as well as the use of these compounds as inhibitors of the proprotein convertases which cleave behind basic P1 residues, especially for inhibition of the protease furin.

Steinmetzer; Torsten

Becker; Gero

Garten; Wolfgang

Philipps-Universitat Marburg

N-terminally modified tetrapeptide derivatives having a C-terminal arginine mimetic

4H-3,1-benzoxazin-4-one derivatives represented by formula (I) below: ##STR1## wherein R.sup.1 represents a lower alkyl group, R.sup.2 represents a lower alkyl group, a lower alkylthioalkyl group, or a lower alkanesulfinylalkyl group, R.sup.3 represents a hydrogen atom a hydroxyl group, a lower alkoxy group, or a lower acyloxy group, X represents an amino acid residue selected from the group consisting of alanine, valine, and phenylalanine, n represents an integer of 0, 1, or 2, and Y means a substituent selected from the group consisting of an alkanoyl group having 2 to 6 carbon atoms which may be substituted by a phenyl group, a benzyloxycarbonyl group, a lower alkoxycarbonyl group, a cinnamoyl group, and a methoxysuccinyl group. These derivatives exhibit a strong serine protease inhibiting effect, and are useful as effective components of agents for preventing and curing diseases caused by the excessive effect of serine proteases, e.g., pneumonia, pulmonary emphysema, fibroid lung, bronchitis, arthritis, pancreatitis, nephritis, shock, sepsis, and arteriosclerosis.

Japan Tobacco, Inc.

4H-3,1-benzoxazin-4-one derivative