127-88-8Relevant articles and documents
Fluorescent cyclic phosphoramide mustards and their cytotoxicity against cancer and cancer stem cells
Bhattacharyya, Sudipta,Acharya, Sourav,Dey, Suman Kr.,Vipparthi, Kavya,Singh, Sandeep,Mukherjee, Arindam
, p. 205 - 215 (2019)
Two fluorescent cyclic phosphoramides, 1,3-dihydronaphtho[1,8-cd][1,2,6]phosphdiazine-2-oxide-(2-bis(2-chloroethyl)amide) (1) and 2,3-dihydro-2-oxo-1H-anthra[1,2-d][1,3,2]diazaphosphole-6,11-dione-2[N,N-bis(2-chloroethyl)]amide (2) were synthesized and ch
Further evidence on the favorable role of the anomeric effect on the cleavage of HepDirect and cyclophosphamide prodrugs
Sartillo-Piscil, Fernando,Quintero, Leticia,Cruz-Gregorio, Silvano,Espinosa-Aguirre, Javier,Elinos-Baez, Carmen M.,H?pfl, Herbert,Serrano, Abel
, p. 9647 - 9654 (2014)
On the basis of previous conformational and configurational studies of 4-aryl-substituted cyclophosph(on)ates derived from D-xylofuranose derivatives, wherein it was proposed that the anomeric effect is involved in the spontaneous isomerization of the P atom and the C4 carbon, and consequently, this unusual behavior was associated with the cleavage of the HepDirect prodrugs. We synthesized an analogous series of 2-amino-2-oxo-1,3,2-dioxaphosphorinanes and performed a conformational and configurational analysis in solution and the solid state followed by an examination of their mutagenic activity. The results showed that the 2-amino-2-oxo-1,3,2-dioxaphosphorinanes with the largest mutagenic activity contain either a 4-methoxyphenyl or 4-fluorophenyl group at C4 carbon and presented a major chair conformation, which is prone to weaken the C4 - O3 bond via the anomeric effect and facilitates the cleavage for the release of the biologically active metabolite. (Chemical Equation Presented).
Synthesis of novel chiral 2-Oxo- And 2-thio-1,3,2-oxazaphospholidines via asymmetric cyclization of L-methionol with (thio)phosphoryl dichlorides
Liu, Ling-Yan,Chen, Ru-Yu,Huang, You
, p. 33 - 38 (2005)
In order to search for novel antitumor and antiviral agents with high activity and low toxicity, a series of chiral 2-thio(oxo)-1,3,2- oxazaphospholidines were synthesized via the reaction of L-methionol with all kinds of (thio)phosphoryl dichlorides in THF in the presence of triethylamine at room temperature. The structures of all of the new compounds were confirmed by elemental analyses, 1H, 31P NMR, and 1R spectra.
In the search for new anticancer drugs, VI. Structural modifications of cyclophosphamide
Sosnovsky,Paul
, p. 1146 - 1155 (1983)
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A simple and convenient protocol for the synthesis of seven- and eight-membered phosphorus heterocycles
Kanduluru, Ananda Kumar,Cirandur, Suresh Reddy
, p. 719 - 722 (2016)
A simple procedure for the synthesis of eight-membered 6-(2-chloroethyl)/bis(2-chloroethyl)-amino-12-oxo-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxides (3a-b) and seven-membered 6-(2-chloroethyl)/bis-(2-chloroethyl)aminodibenzo[d,f][1,3,2]dioxaphosphepin 6-oxides (5a-b) from cyclocondensation of equimolar ratios of 2,2'-dihydroxybenzophenone (1) and 2,2'-dihydroxybiphenol (4), respectively with 2-chloroethylphosphonicdichloride (2a) and bis(2-chloroethyl)phosphoramidic dichloride (2b) in dry toluene in the presence of triethylamine at 45-50 °C is described. All synthesized compounds possessed significant growth inhibition for their antibacteria against Bacillus subtilis and Klebsiella pneumonia and antifungi activity on "Curvularia lunata" and "Aspergillus Niger."
An efficient synthesis of 2-hydroxyethyl N,N,N′ ,N′-tetrakis(2-chloroethyl)phosphorodiamidate
Herr, R. Jason,Zhichkin, Paul,Hernandez-Abad, Pedro E.,Meckler, Harold,Schow, Steven R.
, p. 442 - 444 (2001)
A process for the multikilogram preparation of 2-hydroxyethyl N,N,N′ ,N′-tetrakis(2-chloroethyl)phosphorodiamidate has been achieved in substantially pure form by a short synthetic sequence starting from phosphorus oxychloride and 2 equiv of bis(2-chloroethyl)amine. This process involves a two-step preparation of the intermediate mustard chloride in one pot, followed by the base-catalyzed reaction with excess ethylene glycol. This method has been carried out to provide 2.9 kg of this key drug substance intermediate in 52% overall yield.
Synthesis and Antitumor Effect of Sophoridine Derivatives Bearing an Acyclic Aryloxy Phosphoramidate Mustard Functionality
Dai, Lin-Lin,Li, Dong-Dong,Zhao, Xiu-Mei,Zhi, Shuang,Shen, Hong-Sheng,Yang, Zi-Bo
, p. 417 - 425 (2018/12/05)
To elevate the potency of sophoridine, phosphoramidate mustard motif was incorporated to D-ring opened sophoridine scaffold. A series of acyclic aryloxy phosphoramidate mustard functionalized sophoridine derivatives were synthesized and screened for cytostatic activity in a range of different tumor cell lines (S180, H22, K562, MCF-7, SMMC-7721, and LoVo). All these compounds were shown to be more sensitive to S180 and H22 cells with IC50 values ranging from 2.10 to 7.21?μM. In addition, all targeted derivatives distinctly are more cytotoxic to cancer cells than normal cell L929. Compounds 8b, 8c, 8d, and 8e displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Their potential binding modes with DNA topoisomerase I complex have also been investigated.
Novel sophoridine derivatives bearing phosphoramide mustard moiety exhibit potent antitumor activities in vitro and in vivo
Li, Dongdong,Dai, Linlin,Zhao, Xiumei,Zhi, Shuang,Shen, Hongsheng,Yang, Zibo
, (2018/09/06)
Novel mustard functionalized sophoridine derivatives were synthesized and evaluated for their cytotoxicity against of a panel of various cancer cell lines. They were shown to be more sensitive to S180 and H22 tumor cells with IC50 values ranging from 1.01–3.65 μM, and distinctly were more cytotoxic to cancer cells than normal cell L929. In addition, compounds 7a, 7c, and 7e displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Furthermore, they arrested tumor cells in the G1 phase and induced cellular apoptosis. Their potential binding modes with DNA-Top I complex have also been investigated.
