Substituted heterocyclic compounds and methods of use

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 239/48 (2006.01) A61K 31/506 (2006.01) C07D 401/12 (2006.01) C07D 401/14 (2006.01) C07D 403/12 (2006.01) C07D 403/14 (2006.01) C07D 405/14 (2006.01) C07D 409/14 (2006.01)

Patent

CA 2580838

The present invention relates to pyridines, pyrimidines and derivatives thereof, (I) or a pharmaceutically acceptable salts thereof, wherein X1 is N or CR3; X2 is N or CR4; or -X1=X2- is -C(=O)-N(Ra)- or -N(Ra)-C(=O)-; X3 is N or CR4; X4 is N or CR4; X5 is N or CR6; X6 is N or CR6; wherein only 1, 2 or 3 of X1, X2, X3 and X4 are N; R1 is a saturated partially saturated or unsaturated 5-, 6- or 7-membered, ring containing 0, 1, 2 or 3 atoms selected from N, O and S, wherein the ring is substituted by 0, 1, 2 or 3 substituents. Also included is a method of treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic ~ cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

L'invention se rapporte à des pyridines, pyrimidines et dérivés de celles-ci, (I) ou à leurs sels pharmaceutiquement acceptables, où X1 est N ou CR3 ; X2 est N ou CR4 ; ou -X1=X2- est -C(=O)-N(Ra)- ou -N(Ra)-C(=O)- ; X3 est N ou CR4; X4 est N ou CR4; X5 est N ou CR6 ; X6 est N ou CR6 ; où seulement 1, 2 ou 3 de X1, X2, X3 et X4 sont N ; R1 est un cycle saturé, partiellement saturé, ou insaturé à 5, 6 ou 7 éléments, contenant 0, 1, 2 ou 3 atomes sélectionnés parmi N, O et S, le cycle étant substitué par 0, 1, 2 ou 3 substituants. L'invention concerne également une méthode de traitement des affection suivantes : inflammation, polyarthrite rhumatoïde, maladie de Page, ostéoporose, myélome multiple, uvéite, leucémie myéloïde aiguë ou chronique, destruction des cellules ß du pancréas, arthrose, spondylarthrite ankylosante, arthrite goutteuse, maladie intestinale inflammatoire, syndrome de détresse respiratoire aiguë (SDRA), psoriasis, maladie de Crohn, rhinite allergique, colite ulcéreuse, anaphylaxie, dermite de contact, asthme, dégénérescence musculaire, cachexie, syndrome oculo-urétrosynovial, diabète de type I, diabète de type II, maladies à résorption osseuse, rejet de greffe, maladie d'Alzheimer, attaque cardiaque, infarctus du myocarde, lésions d'ischémie/reperfusion, athérosclérose, accident cérébral, sclérose en plaques, accès pernicieux, sepsie, choc septique, syndrome de choc toxique, fièvre, myalgies dues au VIH-1, VIH-2, VIH3, cytomégalovirus (CMV), grippe, adénovirus, infection due à des virus herpétiques ou zona chez un mammifère, par administration d'une dose efficace du composé susdécrit.

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