DERIVADOS DE PIRAZOLO[1,5-A]PIRIMIDINA SUSTITUIDOS CON HETEROCICLICOS FARMACOLOGICAMENTE ACTIVOS

• Main Authors: ROMAN, Viktor, BORZA, Istvan, BENYEI, Gyula Attila, ELES, Janos, PETRO, Jozsef Levente, GEGO, Csaba Lehel
• Format: Patent
• Language: Spanish
• Published: 22.01.2024
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Refiere a nuevos derivados de pirazolo[1,5-a]pirimidina de formula (I) o sales farmaceuticamente aceptables, metabolitos biologicamente activos, profarmacos, racematos, enantiomeros, diastereomeros, solvatos e hidratos de estos que sirven como moduladores alostericos positivos del receptor GABAB. Dichos derivados se caracterizan porque R1, R2, R3, R4, R5, R6, R7, R8, R9 y R10 se seleccionan de C1-C6alquilo o halo-C1-C6alquilo; R9 y R10 pueden formar juntos el grupo oxo; X representa al grupo -CRxRy, -O- o -S(O)n-; Z al grupo -NR-, -O- o -S(O)2; y R4 mas CRx forman un anillo cicloalquilo. Asimismo, los derivados se seleccionan del grupo de -[(3R)-3-{6-etil-5-metil-2-[trans-4-(trifluorometil)ciclohexil]pirazolo[1,5-a]pirimidin-7-il}-3-metilpiperidin-1-il]etan-1-ona. Tambien, refiere a composiciones farmaceuticas que comprenden uno de los derivados de formula (I) como principio activo en combinacion con dos o mas agentes terapeuticos diferentes; al uso de estos nuevos derivados en el tratamiento y/o prevencion de trastornos psiquiatricos (depresion, esquizofrenia), trastornos del neurodesarrollo (sindrome del cromosoma X fragil) y trastornos cognitivos; y al metodo para la fabricacion de medicamentos utiles en el tratamiento y/o prevencion de dichos trastornos. The invention relates to new pyrazolo[1,5-a]pyrimidine derivatives of formula (I) or pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof that serve as GABAB receptor positive allosteric modulators. The invention also relates to the process for producing such compounds and key intermediates used in the process. The invention further relates to pharmaceutical compositions comprising such compounds optionally in combination with two or more different therapeutic agents and the use of such compounds in methods for treating diseases and conditions mediated and modulated by the GABAB receptor positive allosteric mechanism. The invention also provides a method for manufacture of medicaments useful in the treatment of such disorders.