1408237-40-0Relevant academic research and scientific papers
Pyrrole-Based Macrocyclic Small-Molecule Inhibitors That Target Oocyte Maturation
Gunasekaran, Pethaiah,Lee, So-Rim,Jeong, Seung-Min,Kwon, Jeong-Woo,Takei, Toshiki,Asahina, Yuya,Bang, Geul,Kim, Seongnyeon,Ahn, Mija,Ryu, Eun Kyung,Kim, Hak Nam,Nam, Ki-Yub,Shin, Song Yub,Hojo, Hironobu,Namgoong, Suk,Kim, Nam-Hyung,Bang, Jeong Kyu
, p. 580 - 589 (2017)
Polo-like kinase 1 (PLK1) plays crucial roles in various stages of oocyte maturation. Recently, we reported that the peptidomimetic compound AB103-8, which targets the polo box domain (PBD) of PLK1, affects oocyte meiotic maturation and the resumption of meiosis. However, to overcome the drawbacks of peptidic compounds, we designed and synthesized a series of pyrrole-based small-molecule inhibitors and tested them for their effects on the rates of porcine oocyte maturation. Among them, the macrocyclic compound (E/Z)-3-(2,16-dioxo-19-(4-phenylbutyl)-3,19-diazabicyclo[15.2.1]icosa-1(20),6,17-trien-3-yl)propyl dihydrogen phosphate (4) showed the highest inhibitory activity with enhanced inhibition against embryonic blastocyst formation. Furthermore, the addition of this compound to culture media efficiently blocked the maturation of porcine and mouse oocytes, indicating its ability to penetrate the zona pellucida and cell membrane. We investigated mouse oocytes treated with compound 4, and the resulting impairment of spindle formation confirmed PLK1 inhibition. Finally, molecular modeling studies with PLK1 PBD also confirmed the presence of significant interactions between compound 4 and PLK1 PBD binding pocket residues, including those in the phosphate, tyrosine-rich, and pyrrolidine binding pockets. Collectively, these results suggest that the macrocyclic compound 4 may serve as a promising template for the development of novel contraceptive agents.
Macrocyclic compounds and composition for contraception containing the same
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, (2018/09/08)
The present invention relates to a macrocyclic compound, which specifically binds to a polo-box domain of polo-like phosphorylase-1, which inhibits mammalian oocyte maturation and represented by chemical formula 1, and to a composition for contraception containing the same, wherein the macrocyclic compound, according to the present invention, can be used for contraception by inhibiting oocyte maturation and resumption of meiosis after fertilization, and is safe from proteolytic enzymes as the compound is not in the form of a peptide analogue and has a significantly higher permeability of a zona pellucida and a biological membrane compared to drugs in the form of the peptide analogue.COPYRIGHT KIPO 2018
Stereoselective synthesis of hydroxylated 3-aminoazepanes using a multi-bond forming, three-step tandem process
Ahmad, Sajjad,Sutherland, Andrew
, p. 8251 - 8259,9 (2012/12/12)
A multi-bond forming, three-step tandem process involving a palladium(II)-catalysed Overman rearrangement and a ring closing metathesis reaction has been utilised for the efficient synthesis of a 2,3,6,7-tetrahydro- 3-amidoazepine. Substrate directed epoxidation or dihydroxylation of this synthetic intermediate has allowed the diastereoselective synthesis of hydroxylated 3-aminoazepanes including the syn-diastereomer of the balanol core. Asymmetric synthesis of the 2,3,6,7-tetrahydro-3-amidoazepine motif was also achieved using a chiral palladium(II)-catalyst during the Overman rearrangement.
