Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia.
Biomedical Research and Study Centre, Ratsupites 1, Riga LV-1067, Latvia.
Bioorg Med Chem. 2014 Jul 15;22(14):3654-69. doi: 10.1016/j.bmc.2014.05.011. Epub 2014 May 17.
2-(3-(Naphthalen-2-yl)propanamido)cyclohex-1-enecarboxylic acid and its 6-hydroxynaphthalen-2-yl analogue are well-known hydroxyl-carboxylic acid (HCA) receptor HCA2 agonists. A series of novel aryl derivatives of 2-amidocyclohex-1-ene carboxylic acid that contained rigidity elements, such as an E-double bond, triple bond, and trans or cis-substituted cyclopropane rings, instead of the saturated ethane linker in the amide part of the molecules were designed and synthesized, and the derivatives' potency for the activation of HCA1, HCA2, and HCA3 receptors by 3'-5'-cyclic adenosine monophosphate (cAMP) assay were evaluated. The SAR studies revealed that the rigidifying of appropriate molecules enabled modulation of the potency and selectivity of the HCA2 receptor activation.
2-(3-(萘-2-基)丙酰胺基)环己-1-烯羧酸及其 6-羟基萘-2-基类似物是众所周知的羟基羧酸 (HCA) 受体 HCA2 激动剂。设计并合成了一系列新型的 2-酰胺环己-1-烯羧酸芳基衍生物，这些衍生物包含刚性元件，如 E-双键、三键和反式或顺式取代的环丙烷环，而不是分子酰胺部分中的饱和乙烷连接物，并通过 3'-5'-环腺苷单磷酸 (cAMP) 测定评估了它们对 HCA1、HCA2 和 HCA3 受体激活的效力。SAR 研究表明，适当分子的刚性化能够调节 HCA2 受体激活的效力和选择性。
