Buil Maria Antonia, Calbet Marta, Castillo Marcos, Castro Jordi, Esteve Cristina, Ferrer Manel, Forns Pilar, González Jacob, López Sara, Roberts Richard S, Sevilla Sara, Vidal Bernat, Vidal Laura, Vilaseca Pere
Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
Almirall-Barcelona Science Park Unit, Barcelona Science Park, Josep Samitier 1-5, 08028 Barcelona, Spain.
Eur J Med Chem. 2016 May 4;113:102-33. doi: 10.1016/j.ejmech.2016.02.023. Epub 2016 Feb 11.
Monocyclic and bicyclic ring systems were investigated as the "core" section of a series of diphenylsulphone-containing acetic acid CRTh2 receptor antagonists. A range of potencies were observed and single-digit nanomolar potencies were obtained in both the monocyclic and bicyclic cores. Residence times for the monocyclic compounds were very short. Some of the bicyclic cores displayed better residence times. A methyl group in the northern part of the core, between the head and tail was a necessary requirement for the beginnings of long residence times. Variations of the tail substitution maximised potencies and residence times.
研究了单环和双环环系作为一系列含二苯砜乙酸CRTh2受体拮抗剂的“核心”部分。观察到一系列的活性，单环和双环核心均获得了个位数纳摩尔的活性。单环化合物的驻留时间非常短。一些双环核心表现出更好的驻留时间。核心北部、头部和尾部之间的甲基是长驻留时间开始的必要条件。尾部取代的变化使活性和驻留时间最大化。
