Alfavbeta3 and alfavbeta6 integrin antagonists as...

A - Human Necessities – 61 – K

Patent

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A61K 31/00 (2006.01) A61P 1/16 (2006.01) C07D 213/74 (2006.01) C07D 417/14 (2006.01)

Patent

CA 2540730

This invention relates to inhibition of .alpha.v integrins, especially .alpha.v.szlig.3 and .alpha.v.szlig.6 integrins, by specific antagonists, preferably non-peptidic antagonists, related compounds and compounds with comparable specificity, that downregulate fibrogenesis by inhibiting cell migration and production of pro-fibrogenic molecules (e.g., collagens, TIMP-1) and cytokines (e.g., CTGF) by activated hepatic stellate cells/myofibroblasts, activated epithelia and endothelia. These antagonists alone or in combination with other agents can effectively prevent, mitigate or even reverse development of advanced fibrosis, such as fibrosis/cirrhosis of the liver and fibrosis of other organs, such as lungs, kidneys, intestine, pancreas, skin and arteries.

L'invention concerne l'inhibition des intégrines .alpha.v, en particulier, les intégrines .alpha.v.beta.3 et .alpha.v.beta.6, par des antagonistes spécifiques, de préférence,, des antagonistes non peptides, des composés apparentés et des composés présentant une spécificité comparable, régulant négativement la fibrogénèse par inhibition de la migration cellulaire et production de molécules pro-fibrogènes (par exemple, des collagènes, TIMP-1) et de cytokines (par exemple, CTGF) par des cellules stellaires hépatiques activées/myofibroblastes, des cellules épithéliales ou endothéliales activées. Ces antagonistes, seuls ou combinés à d'autres agents, peuvent prévenir efficacement, atténuer ou même inverser le développement d'une fibrose évoluée, telle que la fibrose/cirrhose du foie ou la fibrose d'autres organes, tels que les poumons, les reins, l'intestin, le pancréas, la peau ou les artères.

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