36727-23-8Relevant academic research and scientific papers
A structure-specific small molecule inhibits a miRNA-200 family member precursor and reverses a type 2 diabetes phenotype
Abegg, Daniel,Adibekian, Alexander,Aikawa, Haruo,Disney, Matthew D.,Haniff, Hafeez S.,Knerr, Laurent,Lemurell, Malin,Liu, Xiaohui,Meyer, Samantha M.,Tong, Yuquan
, p. 300 - 10,311 (2022/02/17)
MicroRNA families are ubiquitous in the human transcriptome, yet targeting of individual members is challenging because of sequence homology. Many secondary structures of the precursors to these miRNAs (pri- and pre-miRNAs), however, are quite different. Here, we demonstrate both in vitro and in cellulis that design of structure-specific small molecules can inhibit a particular miRNA family member to modulate a disease pathway. The miR-200 family consists of five miRNAs, miR-200a, -200b, -200c, -141, and -429, and is associated with type 2 diabetes (T2D). We designed a small molecule that potently and selectively targets pre-miR-200c's structure and reverses a pro-apoptotic effect in a pancreatic β cell model. In contrast, an oligonucleotide targeting the RNA's sequence inhibited all family members. Global proteomics and RNA sequencing analyses further demonstrate selectivity for miR-200c. Collectively, these studies establish that miR-200c plays an important role in T2D, and small molecules targeting RNA structure can be an important complement to oligonucleotides.
CYCLOAROMATIZATION REACTIONS OF METHYL 4-CARBOMETHOXY-5-METHOXY-PENTA-2,4-DIENOATE
Nantz, M. H.,Fuchs, P. L.
, p. 761 - 772 (2007/10/02)
Synthesis of the title compound, 1, is described.Reaction of 1 with β-dicarbonyl compounds or various activated acetone derivatives provides substituted 1,3-benzenedicarboxylates.
Pyrimidine Derivatives and Related Compounds. 39. A Novel Cycloaromatization Reaction of 5-Formyl-1,3-dimethyluracil with Three-Carbon Nucleophiles. Synthesis of Substituted 4-Hydroxybenzoates
Hirota, Kosaku,Kitade, Yukio,Senda, Shigeo
, p. 3949 - 3953 (2007/10/02)
Treatment of 5-formyl-1,3-dimethyluracil (1) with α-substituted acetone derivatives (C-C-C type nucleophiles) such as acetylacetone, acetoacetamide, ethyl acetoacetate, and phenylacetone in basic media affords the corresponding 4-hydroxybenzoates (4).On the other hand, treatment of 1 with cyanoacetamide, a C-C-N type nucleophile, gives the nicotinate 8.A mechanism for this cycloaromatization was proposed on the basis of reaction of 5-formyl-1,3-dimethyluracil-d1 (6) with acetylacetone.
