Synthesis and evaluation of (E)-2-(acrylamido)cyclohex-1-enecarboxylic acid derivatives as HCA1, HCA2, and HCA3 receptor agonists |
| |
| Affiliation: | 1. Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia;2. Biomedical Research and Study Centre, Ratsupites 1, Riga LV-1067, Latvia;1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation;2. I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 620990 Ekaterinburg, Russian Federation;3. Photochemistry Center, Russian Academy of Sciences, 119421 Moscow, Russian Federation;1. Department of Chemistry, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan;2. Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan;3. Biofunctional Imaging, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan;4. Institute of Dental Research, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan;5. Department of Oral Radiology, Osaka Dental University, 1-5-17 Otemae Chuo-ku, Osaka 540-0008, Japan;1. Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China;2. Laboratory of Cell Senescence, Shantou University Medical College, Shantou, Guangdong 515041, China;3. Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China;4. Department of Pathology, Xinan Hospital of Chongqing, Chongqing 400038, China |
| |
| Abstract: | 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. |
| |
| Keywords: | GPR109A HCA2 Niacin Dyslipidemia Agonist cAMP 2-Acrylamidocyclohex-1-ene |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
