Sanofi

Sanofi-aventis

Carsten Struebing

Heinz-Werner Kleemann

Marc Nazare

Nis Halland

Tilo Weiss

Friedemann Schmidt

Marc Nazaré

Joachim Saas

Susanne Miehe

The present invention relates to N-(4-(azaindazol-6-yl)-phenyl)-sulfonamides of the formula I, wherein Ar, n, X, Z, R1, R2 and R3 have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds which modulate protein kinase activity, specifically the activity of serum and glucocorticoid regulated kinase (SGK), in particular of serum and glucocorticoid regulated kinase isoform 1 (SGK-1, SGK1), and are suitable for the treatment of diseases in which SGK activity is inappropriate, for example degenerative joint disorders or inflammatory processes such as osteoarthritis or rheumatism. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use as pharmaceuticals, and pharmaceutical compositions comprising them.

N-(4-(azaindazol-6-yl)-phenyl)-sulfonamides and their use as pharmaceuticals

TRPC ion channels are non-selective channels widely expressed in human tissues. These channels are involved in numerous physiological functions and are putative targets for the development of novel medicines. There is a need to gain a better understanding of TRPC ion channels in cells and beyond. The present invention provides a pharmacological tool compound that allows to study TRPC ion channels due to its discriminating inhibition of TRPC subfamilies. In the present invention, norgestimate is shown to selectively inhibit TRPC3, TRPC6 and TRPC7.

Use of norgestimate as a selective inhibitor of TRPC3, TRPC6 and TRPC7 ion channels

The invention refers to the use of a TRPC channel, an inactivating mutant thereof, or a nucleotide sequence coding for the TRPC channel or for the inactivating mutant for the production of a medicament for the treatment of a cardiovascular disease and a method of screening a modulator of the TRPC channel or an inactivating mutant thereof.

Improving vascular function with an inactivating mutant of a TRPC channel protein

Treating cardiovascular disease with TRPC3 channel protein

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Frankfurt-am-Main, Germany

Carsten Struebing