35661-51-9Relevant articles and documents
Bone-targeted acid-sensitive doxorubicin conjugate micelles as potential osteosarcoma therapeutics
Low, Stewart A.,Yang, Jiyuan,Kopeek, Jindich
, p. 2012 - 2020 (2014)
Osteosarcoma is a malignancy of the bone that primarily affects adolescents. Current treatments retain mortality rates, which are higher than average cancer mortality rates for the adolescent age group. We designed a micellar delivery system with the aim to increase drug accumulation in the tumor and potentially reduce side effects associated with chemotherapy. The design features are the use of the hydrophilic d-aspartic acid octapeptide as both the effective targeting agent as well as the hydrophilic micelle corona. Micelle stabilization was accomplished by binding of model drug (doxorubicin) via an acid-sensitive hydrazone bond and incorporating one to four 11-aminoundecanoic acid (AUA) moieties to manipulate the hydrophobic/hydrophilic ratio. Four micelle-forming unimers have been synthesized and their self-assembly into micelles was evaluated. Size of the micelles could be modified by changing the architecture of the unimers from linear to branched. The stability of the micelles increased with increasing content of AUA moieties. Adsorption of all micelles to hydroxyapatite occurred rapidly. Doxorubicin release occurred at pH 5.5, whereas no release was detected at pH 7.4. Cytotoxicity toward human osteosarcoma Saos-2 cells correlated with drug release data.
A hydroxamic-acid-containing nucleoside inhibits DNA repair nuclease SNM1A
Doherty, William,Dürr, Eva-Maria,Baddock, Hannah T.,Lee, Sook Y.,McHugh, Peter J.,Brown, Tom,Senge, Mathias O.,Scanlan, Eoin M.,McGouran, Joanna F.
supporting information, p. 8094 - 8105 (2019/09/19)
Nine modified nucleosides, incorporating zinc-binding pharmacophores, have been synthesised and evaluated as inhibitors of the DNA repair nuclease SNM1A. The series included oxyamides, hydroxamic acids, hydroxamates, a hydrazide, a squarate ester and a squaramide. A hydroxamic acid-derived nucleoside inhibited the enzyme, offering a novel approach for potential therapeutic development through the use of rationally designed nucleoside derived inhibitors.
Synthetic method of Fmoc-Aza-beta3Leu-OH
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Paragraph 0032; 0033; 0034, (2018/07/07)
The invention discloses a synthetic method of Fmoc-Aza-beta3Leu-OH. The method comprises the following steps: enabling FMOC-Cl and hydrazine hydrate to have nucleophilic substitution to obtain FMOC-based formate as shown in formula A1; enabling 2-methyl propanal and the obtained Fmoc-based formate as shown in the formula A1 to have condensation reaction to obtain hydrazone as shown in formula A2;enabling the obtained hydrazone as shown in the formula A2 to have reduction reaction with reducing agent sodium cyanoborohydride to obtain Fmoc-Azabeta3Leu hydrazone as shown in formula A3; then enabling the Fmoc-Azabeta3Leu hydrazone as shown in the formula A3 to have nucleophilic substitution with tert-butyl bromoacetate to obtain FmocAza-beta3Leu-OtBu as shown in formula A4; and finally enabling the obtained FmocAza-beta3Leu-OtBu as shown in the formula A4 to have degreasing reaction with dichloromethane introduced with HCl gas to obtain a target product FmocAza-beta3Leu-OH as shown in formula A5. The preparation method provided by the invention is mild in reaction condition, a Fmoc protective group can be easily removed by utilizing a mild alkaline condition, the operation is simple,the route is simple and effective, and the applicability is wide.
A New Method for the Synthesis of Oxadiazine Insecticide Indoxacarb
Xu, Defeng,Guan, Jing,Xu, Xing,Gong, Shunze,Xu, Hui
, p. 1469 - 1473 (2016/09/23)
9-Fluorenylmethoxycarbonyl was a good protecting group in the field of chemical industry. In the present paper, a new approach for the synthesis of oxadiazine insecticides indoxacarb used 9-fluorenylmethoxycarbonyl as protected group, and triphosgene for chloroformylation. A convenient synthesis of 9-fluorenylmethoxycarbonylhydrazine can be achieved by the nucleophilic substitution reaction of 9-fluorenylmethyl chloroformate and hydrazine hydrate. 4a-Methyl-2-(9-fluorenylmethyl)-7-chloro-indeno [1,2e][1,3,4]oxadia zine-2,4a (3H,5H)-dicarboxylate can be produced via ketone -hydrazine crosslink reaction and cyclization. A preparation of carbamic acid-(chlorocarbonyl)-[(4-trifluoromethoxy) phenyl] me ester can be obtained by the chloroformylation of triphosgene. Finally, the deprotection of 9-fluorenylmethoxy carbonyl and condensation with carbamic acid-(chlorocarbonyl)-[(4-trifluoromethoxy) phenyl] me ester can afford indoxacarb in good yield. A new method for the synthesis of oxadiazine insecticides indoxacarb used 9-fluorenylmethoxycarbonyl-protected group to produce 9-?fluorenylmethoxycarb?onylhydrazine, then through the ketone–hydrazine crosslink reaction, cyclization, deprotection, chloroformylation, and condensation in good yield.
