Novel therapeutic agents that modulate neurokinin receptors

Details Novel therapeutic agents that modulate neurokinin receptors Novel therapeutic agents that modulate neurokinin receptors

A - Human Necessities

61

K

A61K 31/445 (2006.01) A61K 38/00 (2006.01) A61K 39/00 (2006.01) A61K 39/395 (2006.01) A61K 39/44 (2006.01) A61K 51/00 (2006.01) C07B 61/00 (2006.01) C07C 215/60 (2006.01) C07C 217/08 (2006.01) C07C 323/62 (2006.01) C07D 211/42 (2006.01) C07D 211/56 (2006.01) C07D 213/74 (2006.01) C07D 213/80 (2006.01) C07D 263/32 (2006.01) C07D 263/34 (2006.01) C07D 265/32 (2006.01) C07D 277/24 (2006.01) C07D 277/28 (2006.01) C07D 277/34 (2006.01) C07D 401/00 (2006.01) C07D 401/12 (2006.01) C07D 401/14 (2006.01) C07D 413/06

Patent

CA 2319159

Novel multi-binding compounds (agents) which bind neurokinin receptors are used to treat disorders in mammals that are mediated by the neurokinin receptors, such as Parkinson's disease, Alzheimer's disease, depression, anxiety, inflammation, rheumatoid arthritis, cystitis, osteoarthritis, irritable bowel syndrome, allergic rhinitis, pain, chronic pain, migraine headaches, asthma, bronchitis and chemotherapy induced emesis. The compounds of this invention comprise a plurality of ligands each of which can bind to such receptors thereby modulating the biological processes/functions thereof. Each of the ligands is covalently attached to a linker or linkers which may be the same or different to provide for the multi-binding compound. The linker is selected such that the multi-binding compound so constructed demonstrates increased modulation of the biological processes mediated by the neurokinin receptor. The invention is also directed to pharmaceutical compositions comprising the multi-binding compounds, methods of inhibiting and treating the disorders mediated by neurokinin receptors, and methods of preparing multi- binding compounds of the invention.

L'invention concerne des nouveaux composés (agents) de liaison multiple se liant aux récepteurs des neurokinines, et que l'on utilise pour traiter, chez les mammifères, des troubles induits par les récepteurs des neurokinines, comme la maladie de Parkinson, la maladie d'Alzheimer, la dépression, l'anxiété, l'inflammation, la polyarthrite rhumatoïde, la cystite, l'ostéo-arthrite, la colopathie fonctionnelle, la rhinite allergique, la douleur, la douleur chronique, les migraines, l'asthme, la bronchite et les vomissements induits par la chimiothérapie. Les composés de l'invention comprennent plusieurs ligands, chacun pouvant se lier à de tels récepteurs, modulant ainsi les processus/fonctions biologiques de ceux-ci. Chaque ligand est attaché de manière covalente à un (des) segment(s) de liaison, lesquels peuvent être semblables ou différents, afin de constituer le composé de liaison multiple. On a choisi le segment de liaison de manière que le composé de liaison multiple ainsi construit démontre une propriété accrue de modulation des procédés biologiques induits par le récepteur des neurokinines. L'invention concerne également des compositions pharmaceutiques contenant les composés de liaison multiple, des méthodes d'inhibition et de traitement des troubles induits par les récepteurs des neurokinines, ainsi que des procédés de préparation des composés de liaison multiple de l'invention.

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