Octahydro-pyrrolo[3,4-b] pyrrole derivatives and their use...

C - Chemistry – Metallurgy – 07 – D

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C07D 487/04 (2006.01) A61K 31/407 (2006.01)

Patent

CA 2641624

Octahydro-pyrrolo[3,4-b]pyrrole derivatives or a pharmaceutically acceptable salt, ester, amide, prodrug, or radiolabeled form thereof, wherein R1 is alkyl, C3-C5 cycloalkyl. or (C3-C5 cycloalkyl)methyl; R2a, R2b, R2c, R2d, R2e, and R2f each are independently hydrogen, methyl, or fluoromethyl; R3a, R3b, R3c, and R3d each are independently hydrogen, alkyl, fluoroalkyl, fluoroalkoxy, alkoxy, thioalkoxy, halogen, or nitrile, with the proviso that when one or more of R3a, R3b, R3c, and R3d are alkyl, then at least one of R3a, R3b, R3c, and R3d is fluoroalkyl, fluoroalkoxy, alkoxy, thioalkoxy, halogen, or nitrile; L1 is a bond, oxygen, sulfur, carbonyl, alkylene,. alkylcarbonyl, alkylamino, -C(=N-Oalkyl)-, NR4, -C(=O) NR4-, or -NR4C(=O)-; R4 is hydrogen or alkyl; Cy1 is aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocycle; Z is a substituent R6 or a group represented by -L3-Cy3; R6 is hydrogen, acyl, acyloxy, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxyimino, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkynyl, amido, carboxy, cyano, cycloalkyl, fiuoroalkoxy, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, nitro, alkylthio, amino, NHR7, NR7R8, -N(R7)C(=O)R9, -C(=O)NR7R8, or N(R7)SO2(R10); L3 is a bond, oxygen, sulfur, carbonyl, alkylene, alkylcarbonyl, alkylamino, - C(=N-Oalkyl)-, NR11, -C(=O) NR11-, or -NR11C(=O)-;Cy3 is aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocycle; R7, R8, R9, R10, and R11 at each occurrence are independently hydrogen,C1-4 alkyl, C3-C4 cycloalkyl, or a (C3- C4 cycloalkyl)amine; are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands. Octahydro-pyrrolo[3,4- b]pyrrole compounds, methods for using such compounds, compositions for making them, and processes for preparing such compounds are disclosed herein.

L'invention concerne des dérivés d'octahydro-pyrrolo[3,4-b]pyrrole utiles pour le traitement d'états ou de troubles prévenus ou améliorés par les ligands du récepteur d'histamine-3. L'invention concerne également des composés d'octahydro-pyrrolo[3,4-b]pyrrole, des procédés d'utilisation de tels composés, des compositions pour leur fabrication et des procédés de préparation de tels composés.

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