DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO

• Main Authors: BRADLEY TEEGARDEN, PETER IAN DOSA, HONNAPPA JAYAKUMAR, SONJA STRAH-PLEYNET, HONGMEI LI
• Format: Patent
• Language: Croatian; English
• Published: 31.03.2007
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

Spoj, naznačen time, da je izabran među spojevimaFormule (I) i njihovim farmaceutski prihvatljivimsolima, hidratima i solvatima; gdje: R1 je aril ili heteroaril svaki po izboru supstituiran sa R9, R10, R11, R12, R13, R14 i R15 od kojih je svaki nezavisno izabran između: C1-6 acil, C1-6 aciloksi, C2-6 alkenil, C1-6 alkoksi, C1-6 alkil, C1-6 alkilkarboksamid, C1-6 alkinil, C1-6 alkilsulfonamid, C1-6 alkilsulfinil, C1-6 alkilsulfonil, C1-6 alkiltio, C1-6 alkilureil, amino, C1-6 alkilamino, C2-8 dialkilamino, C1-6 alkilimino, karbo-C1-6-alkoksi,karboksamid, karboksi, cijano, C3-7 cikloalkil, C2-8 dialkilkarboksamid, C2-8 dialkilsulfonamid, halogen, C1-6 haloalkoksi, C1-6 haloalkil, C1-6 haloalkilsulfinil, C1-6 haloalkilsulfonil, C1-6 haloalkiltio, heterocikl, hidroksi, tiol, nitro, fenoksii fenil, ili dva susjedna R9, R10, R11, R12, R13,R14 i R15 zajedno s atomima na koje su vezani čine C5-7 cikloalkil skupinu ili heterocikličku skupinu od kojih je svaka po izboru supstituirana s F, Cl, ili Br; te gdje su spomenuti C2-6 alkenil, C1-6 alkil, C2-6alkinil, C1-6 alkilamino, C2-8 dialkilamino, heterocikli i fenil po izboru supstituirani s 1 do 5 supstituenada nezavisno izabranih između: C1-6 acil, C1-6 aciloksi, C2-6 alkenil, C1-6 alkoksi, C1-6 alkil, C1-6 alkilkarboksamid, C2-6 alkinil, C1-6 alkilsulfonamid, C1-6 alkilsulfinil, C1-6 alkilsulfonil, C1-6 alkiltio, C1-6 alkilureil, amino, C1-6 alkilamino, C2-8 dialkilamino, karbo-C1-6-alkoksi, karboksamid, karboksi, cijano, C3-7 cikloalkil, C2-8 dialkilkarboksamid, halogen, C1-6 haloalkoksi, C1-6 haloalkil, C1-6 haloalkilsulfinil, C1-6 haloalkilsulfonil, C1-6 haloalkiltio, hidroksi, tiol i nitro; R2 je izabran između: -H, C1-6alkil, C2-6 alkenil, C2-6 alkinil i C3-7 cikloalkil; R3 je izabran između: -H, C2-6 alkenil, C1-6 alkil, C1-6 alkilkarboksamid, C2-6 alkinil, C1-6 alkilsulfonamid, karbo-C1-6-alkoksi, karboksamid, karboksi, cijano, C3-7 cikloalkil, C2-8 dialkilkarboksamid, halogen, heteroaril i fenil; i gdje svaka od navedenih C2-6 alkenil, C1-6 alkil, C2-6 alkinil, C1-6 alkilsulfonamid, C3-7 cikloalkil, heteroaril i fenil skupina može biti po izboru supstituirana s 1 do 5 supstituenada izabranih nezavisno između: C1-5 acil, C1-5 aciloksi, C2-6 alkenil, C1-4 alkoksi, C1-8 alkil, C1-6 alkilamino, C2-8 dialkilamino, C1-4 alkilkarboksamid, C2-6 alkinil, C1-4 alkilsulfonamid, C1-4 alkilsulfinil, C1-4 alkilsulfonil, C1-4 alkiltio, C1-4 alkilureil, amino, karbo-C1-6-alkoksi, karboksamid, karboksi, cijano, C3-6 cikloalkil, C2-6 dialkilkarboksamid, halogen, C1-4haloalkoksi, C1-4 haloalkil, C1-4 haloalkilsulfinil, C1-4 haloalkilsulfonil, C1-4 haloalkiltio, hidroksi, nitro i sulfonamid; R4 je izabran između: -H, C1-6 acil, C1-6 aciloksi, C2-6 alkenil, C1-16 alkoksi, C1-6 alkil, C1-6 alkilkarboksamid, C2-6 alkinil, C1-6 alkilsulfonamid, C1-6 alkilsulfinil, C1-6 alkilsulfonil, C1-6 alkiltio, C1-6 alkilureil,amino, C1-6 alkilamino, C2-8 dialkilamino, karbo-C1-6-alkoksi, karboksamid, karboksi, cijano, C3-7 cikloalki The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor.Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like.The present invention also relates to the method of prophylaxis or treatment of 5-HT2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.