DANIEL OBRECHT,PHILIPP ERMERT,SAID OUMOUCH,ARNAUD PIETTRE,JEAN-FRANÇOIS GOSALBES,MARC THOMMEN
申请号：
MX2014011078
公开号：
MX2014011078A
申请日:
2013.03.15
申请国别(地区):
MX
年份:
2014
代理人:
摘要：
The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1 ) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases.El sistema de anillo macrocíclico de la formula (I) definido espacialmente y restringido de modo conformacional, se encuentra constituido por tres partes moleculares distintas: Plantilla A, Modulador B de conformación y Puente C. Los macrociclos descritos por este sistema de anillo I se fabrican fácilmente por síntesis en paralelo o química combinatorial en solución o en fase sólida. Se diseñan para interactuar con una variedad de clases de objetivos biológicos específicos, ejemplos son su actividad agonista o antagonista sobre los receptores acoplados a la proteína G (GPCR), la actividad inhibidora sobre las enzimas o su actividad antimicrobiana. En particular, estos macrociclos muestran una actividad inhibidora en la enzima que convierte endotelina del subtipo 1 (ECE-1) y/o la cisteína proteasa de catepsina S (CatS), y/o actúan como antagonistas del receptor de oxitocina (OT), el receptor de hormona que l
