Certain pyrazole derivatives as corticotropin-releasing...

C - Chemistry – Metallurgy – 07 – D

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C07D 401/06 (2006.01) A61K 31/415 (2006.01) C07D 231/12 (2006.01) C07D 231/14 (2006.01)

Patent

CA 2272066

Disclosed are compounds that are highly selective partial agonists or antagonists at human CRF1 receptors that are useful in the diagnosis and treatment of treating stress related disorders such as post stress disorder (PTSD) as well as depression, headache and anxiety. The compounds have formula (I) or the pharmaceutically acceptable salts thereof wherein Ar is phenyl, 1- or 2- naphthyl, 2-, 3-, or 4-pyridinyl, 2- or 3-thienyl, 4- or 5-pyrimidinyl, mono, disubstituted, or trisubstituted with halogen, hydroxy, C1-C6 alkyl, C1- C6 alkoxy with the proviso that at least one of the positions on Ar ortho to the point of attachment to the pyrazole ring is substituted; A is CH2 or C=O; R1 is hydrogen, C1-C6 alkyl; R2 is hydrogen, C1-C6 alkyl, or C1-C6 alkenyl; Z is a group of formula (a); Z is -NR6R7.

L'invention porte sur des composés constituant des agonistes ou antagonistes partiaux hautement sélectifs des récepteurs humains du CRF¿1? pouvant servir au diagnostic ou au traitement de troubles liés au stress tels que les troubles dus aux stress post-traumatiques (PTSD), la dépression, la migraine ou l'anxiété. Il s'agit des composants de formule (I) ou de leurs sels pharmacocompatibles. Dans ladite formule: Ar est phényl, 1- ou 2-naphtyl, 2-, 3-, 4-pyridinyl, 2- ou 3-thiényl, 4- ou 5- pyrimidinyl à mono-, di- ou trisubstitution halogène, hydroxy, C¿1?-C¿6? alkyl ou C¿1?-C¿6? alcoxy, sous réserve d'au moins une substitution des positions sur Ar en ortho par rapport au point de liaison au cycle pyrazol; A est CH¿2? ou C=O; R¿1? est hydrogène ou C¿1?-C¿6? alkyl; R¿2? est hydrogène, C¿1?-C¿6? alkyl ou C¿1?-C¿6? alcényl; et Z est un groupe -NR¿6?R¿7? représenté par la formule spécifique (a).

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