Novartis Ag

Motowo Nakajima

Junichi Sakaki

Werner Breitenstein

Shinichiro Matsunaga

Genji Iwasaki

Kenji Hayakawa

Takanori Kanazawa

Shinichi Koizumi

Paivi Jaana Kukkola

Tatsuhiko Kasaoka

Leslie Ann Robinson

Leslie Anne Robinson

Minako Funakubo

&#x3b1;-Amino hydroxamic acid derivative of the formula I, in which R is C-C-alkyl, which is mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C-C-cycloalkyl or unsubstituted or substituted C-C-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; or C-C-alkenyl or C-C-alkynyl, which in each case is unsubstituted or mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C-C-cycloalkyl or unsubstituted or substituted C-C-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N;and the other symbols are as defined in claimare described. These compounds are MMP and in particular MMP2 inhibitors and can be used for treatment of MMP dependent diseases, in particular inflammation conditions, rheumatoid arthritis, osteoarthritis, tumors (tumor growth, metastasis, progression or invasion) and pulmonary disorders (e.g. emphysema, COPD).

Arylsulfonamido-substituted hydroxamic acid derivatives

&#x3b1;-Amino hydroxamic acid derivative of formula (I), in which R is C&#x2013;C-alkyl, which is mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C&#x2013;C-cycloalkyl or unsubstituted or substituted C&#x2013;C-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; or C&#x2013;C-alkenyl or C&#x2013;C-alkynyl, which in each case is unsubstituted or mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C&#x2013;C-cycloalkyl or unsubstituted or substituted C&#x2013;C-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; and the other symbols are as defined in claim, are described. These compounds are MMP and in particular MMP2 inhibitors and can be used for treatment of MMP dependent diseases, in particular inflammation conditions, rheumatoid arthritis, osteoarthritis, tumors (tumor growth, metastasis, progression or invasi n) and pulmonary disorders (e.g. emphysema, COPD).

This invention relates to identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, a polypeptide of the present invention is &ldquo;heparanase&rdquo;obtainable from the human SV40-transformed fibroblast cell line ATCC CCL 75.1. The heparanase is an endoglucuronidase capable of specifically degrading heparan sulfate into 6 to 20 kDa fragments.

Human heparanase polypeptide and cDNA

Compounds of formula (I) wherein W is &mdash;OH or &mdash;NHOH; X is an optionally substituted heterocycle, NR SO R , heterocyclylalkythio, CONR R or NR COR ; Y, Z, R -R and n are as defined in the application. Compounds (I) are inhibitors of matrix-degrading metalloproteinases and are use for the treatment of related conditions.

Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases

Sulfonylamino acid and sulfonylamino hydroxamic acid derivatives

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Ashiya, Japan

Motowo Nakajima