41-Azido-41-deoxyrapamycin

Xie, Lijun; Huang, Jie; Zuo, Jian; Yu, Heng; Yuan-rong, Cheng

doi:10.1107/s1600536812012548

Cited by 2 publications

(3 citation statements)

References 9 publications

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“…Despite two years of efforts, we had never been able to obtain single crystals of these quaternary ammonium salt derivatives, so we tried to simulate the 3D structure of typical compounds 1 and 7 . Given the structure of rapamycin was extremely complicated, we attempted to construct this 3D structure based on the X-ray single crystal data of rapamycin reported by Swindel [16,17,18].…”

Section: Resultsmentioning

confidence: 99%

Selective Substitution of 31/42–OH in Rapamycin Guided by an in Situ IR Technique

Cao

Zhou²,

Yang

et al. 2014

Molecules

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An in situ IR technique was applied in the selective synthesis of the key intermediate for rapamycin derivatives, which made the reaction endpoint easily defined. This technology solved a bothersome problem in the preparation of rapamycin derivatives, and based on this technique, the 31-OH and 42-OH of rapamycin were chemically modified by a series of quaternary ammonium salts to generate 11 compounds. The solubility of all these compounds was remarkably improved (25,000 times higher than that of rapamycin) and their structures were confirmed by MS, IR, 1D and 2D NMR techniques.

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Section: Resultsmentioning

confidence: 99%

Selective Substitution of 31/42–OH in Rapamycin Guided by an in Situ IR Technique

Cao

Zhou²,

Yang

et al. 2014

Molecules

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“…27) Thus, the azido compound (2) was synthesized from rapamycin (1) via triflate activation of the C- 43 hydroxyl group followed by treatment with sodium azide according to our reported procedure. 28) Meanwhile, it should be pointed out that this method involves an S N 2 process and therefore gives rise to inversion of configuration at C-43. As already observed in our previous work, 28) the stereochemistry of compound (2) had been determined by single crystal X-ray diffraction studies.…”

Section: Resultsmentioning

confidence: 99%

“…28) Meanwhile, it should be pointed out that this method involves an S N 2 process and therefore gives rise to inversion of configuration at C-43. As already observed in our previous work, 28) the stereochemistry of compound (2) had been determined by single crystal X-ray diffraction studies. Next, the azido compound (2) was transformed to C43-aminorapamycin (3) via Staudinger reduction, which subsequently reacted with side chains (12) to afford targeted compounds (4a-e, 5a-c) as white powder.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Novel Rapamycin Benzothiazole Hybrids as mTOR Targeted Anti-cancer Agents

Xie

Huang

Chen

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The immunosuppressant drug rapamycin, was firstly identified as a mammalian target of rapamycin (mTOR) allosteric inhibitor, and its derivatives have been successfully developed as anti-cancer drugs. Therefore, finding rapamycin derivatives with better anti-cancer activity has been proved to be an effective way to discover new targeted anti-cancer drugs. In this paper, structure modification was performed at the C-43 position of rapamycin using bioisosterism and a hybrid approach: a series of novel rapamycin-benzothiazole hybrids 4a-e, 5a-c, and 9a, b have been designed, synthesized and evaluated for their anti-cancer activity against Caski, CNE-2, SGC-7901, PC-3, SK-NEP-1 and A-375 human cancer cell lines. Some of these compounds (4a-e, 9a, b) displayed good to excellent potency against the Caski and SK-NEP-1 cell line as compared with rapamycin. Compound 9b as the most active compound showed IC 50 values of 8.3 (Caski) and 9.6 μM (SK-NEP-1), respectively. In addition, research on the mechanism showed that 9b was able to cause G1 phase arrest and induce apoptosis in the Caski cell line. Most importantly, it significantly decreased the phosphorylation of S6 ribosomal protein, p70S6K1 and 4EBP1, which indicated that 9b inhibited the cancer cell growth by blocking the mTOR pathway and may have the potential to become a new mTOR inhibitor.Key words rapamycin; benzothiazole; hybrid approach; anti-cancer activity Rapamycin, a 31-member polyketide macrolide, was discovered as a fermentation product of the Streptomyces hygroscopicus AYB-944 and FC904, best known as a potent immunosuppressive agent later.

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41-Azido-41-deoxyrapamycin

Cited by 2 publications

References 9 publications

Selective Substitution of 31/42–OH in Rapamycin Guided by an in Situ IR Technique

Selective Substitution of 31/42–OH in Rapamycin Guided by an in Situ IR Technique

Design, Synthesis and Biological Evaluation of Novel Rapamycin Benzothiazole Hybrids as mTOR Targeted Anti-cancer Agents

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