2-3-disubstituted quinuclidines as modulators of monoamine...

C - Chemistry – Metallurgy – 07 – D

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C07D 453/04 (2006.01) A61K 31/439 (2006.01) A61P 25/00 (2006.01) C07D 211/52 (2006.01) C07D 453/02 (2006.01) C07D 491/04 (2006.01)

Patent

CA 2420235

The present invention relates to a class of compounds of formula (I) and (II): wherein R1 is hydrogen; linear or branched C1-C15 alkyl; C1-C15 alkenyl; C3-C6 cycloalkyl; mono, di, tri, tetra, penta substituted aryl or heteroaryl; COOR3; -(CH2)n-aryl; -COO-(CH2)nR3;-(CH2)n-COOR3;-C(O)R3;-C(O)NHR3; or an unsubstituted or substituted oxadiazole; and R2 hydrogen; linear or branched C1-C15 alkyl; C1-C15 alkenyl; C3-C6 cycloalkyl; mono, di, tri, tetra, penta substituted aryl or heteroaryl; unsubstituted or substituted naphthyl; 1, 3- Benzodioxole; fluorine; indole; isoquinoline; quinoline; pyridine; pyrimidine; onnthracene; or-(CH2)n-Ph; wherein the heteroaryl comprises N, O, or S, the mono or multi substituents on the aryl or heteroaryl are independently C1-C5 alkyl, C1-C5 alkenyl, H, F, Cl, Br, I NO2, NHR , or OR, R is C1-C7 alkyl; R3 is C1-C5 alkyl, C1-C5 alkenyl, benzyl, substituted aryl or heteroaryl; and n = 1-7. These compounds are discovered , synthesized and confirmed as potent inhibitors of dopamine (DA), serotonin (5-HT),and norepinephrine inhibitors. These compounds are therefore particularly useful in the treatment conditions or diseases wherein modulation of the monoamine neurotransmitter system involving dopamine (DA), serotonin (5-HT), and norepinephrine plays a role.

La présente invention concerne une classe de composés de formule (I) et (II), dans lesquelles R¿1? représente hydrogène, alkyle C¿1?-C¿15? linéaire ou ramifié, alcényle C¿1?-C¿15?, cycloalkyle C¿3?-C¿6?, aryle ou hétéroaryle mono, di, tri, tétra ou penta-substitué, COOR¿3?, -(CH¿2?)¿n?-aryle, -COO-(CH¿2?)¿n?R¿3?, -(CH¿2?)¿n?-COOR¿3?, -C(O)R¿3?, -C(O)NHR¿3? ou oxadiazole non substitué ou substitué, R¿2? représente hydrogène, alkyle C¿1?-C¿15? linéaire ou ramifié, alcényle C¿1?-C¿15?, cycloalkyle C¿3?-C¿6?, aryle ou hétéroaryle mono, di, tri, tétra ou penta-substitué, naphtyle non substitué ou substitué, 1,3-benzodioxole, fluorène, indole, isoquinoline, quinoline, pyridine, pyrimidine, anthracène ou -(CH¿2?)¿n?-Ph, l'hétéroaryle comprenant N, O ou S et le ou les substituants sur aryle ou sur hétéroaryle représentent indépendamment alkyle C¿1?-C¿5?, alcényle C¿1?-C¿5?, H, F, Cl, Br, I, -NO2, NHR ouOR, R étant alkyle C¿1?-C¿7?, R¿3? représente alkyle C¿1?-C¿5?, alcényle C¿1?-C¿5?, benzyle, aryle ou hétéroaryle substitué et n vaut de 1 à 7. Ces composés ont été découverts et synthétisés, puis leur rôle d'inhibiteurs puissants de dopamine (DA) et de sérotonine (5-HT) et d'inhibiteurs de norépinéphrine a été confirmé. Ces composés sont notamment utilisés dans le traitement de pathologies ou de maladies dans lesquelles la modulation du système de neurotransmetteurs de monoamine impliquant la dopamine (DA), la sérotonine (5-HT) et la norépinéphrine joue un rôle.

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