Short-step synthesis and structure-activity relationship of cortistatin A analogs
| Autor: | Naoyuki Kotoku, Shunichi Shibuya, Masaki Nogata, Aoi Ito, Aki Takeshima, Motomasa Kobayashi, Kanako Mizuno |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
010405 organic chemistry
Stereochemistry Organic Chemistry Improved method 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Cortistatin 0104 chemical sciences chemistry.chemical_compound chemistry Drug Discovery Side chain Moiety Molecule Structure–activity relationship Isoquinoline Acetamide |
| Zdroj: | Tetrahedron. 73:1342-1349 |
| ISSN: | 0040-4020 |
| DOI: | 10.1016/j.tet.2017.01.042 |
| Popis: | An improved method for synthesizing structurally simplified analogs of cortistatin A (1), a novel anti-angiogenic steroidal alkaloid from a marine sponge, was developed. In contrast to previous methods, step- and redox-economical synthesis was achieved using a known α-bromoketone as the starting material. The structure-activity relationship study revealed that the isoquinoline portion was strictly recognized by the target molecule. Surprisingly, the introduction of the acetamide moiety on the A-ring structure dramatically enhanced the selective antiproliferative activity against endothelial cells. This new method can be easily applied to gram-scale synthesis and enabled us to prepare various analogs, which were focused on the participation of the side chain and A-ring structure. |
| Databáze: | OpenAIRE |
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