Tian, Zong-Qiang published the artcilePotent Cytotoxic C-11 Modified Geldanamycin Analogues, Synthetic Route of 795299-77-3, the publication is Journal of Medicinal Chemistry (2009), 52(10), 3265-3273, database is CAplus and MEDLINE.
17-Allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the activity of Hsp90, an important target for treatment of cancers. In an effort to identify analogs of geldanamycin (GDM) with properties superior to those of 17-AAG, we synthesized C-11 modified derivatives of GDM including ethers, esters, carbazates, ketones, and oximes, and measured their affinity for Hsp90 and their ability to inhibit growth of human cancer cells. In accordance with crystal structures reported for complexes of GDMs with Hsp90, bulky groups attached to C-11 interfered with Hsp90 binding while smaller groups such as 11-O-Me allowed Hsp90 binding. In addition, these analogs also showed in vitro cytotoxicity against human cancer cell lines. Esterfication of the 11-OH of 17-AAG eliminated Hsp90 binding in vitro. The readily hydrolyzed esters acted as prodrugs during the measurement of cytotoxicity. Thus, during these experiments, the esters were hydrolyzed, releasing 17-AAG. Several 11-O-methyl-17-alkylaminogeldanamycin analogs were identified with improved potency relative to 17-AAG.
Journal of Medicinal Chemistry published new progress about 795299-77-3. 795299-77-3 belongs to quinuclidine, auxiliary class Azetidine,Amine, name is 2-(Azetidin-1-yl)ethanamine, and the molecular formula is C8H16O2, Synthetic Route of 795299-77-3.
Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider