170935-63-4Relevant academic research and scientific papers
Preparation method of cytarabine 5'-O-L-valine ester hydrochloride
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Page/Page column 5, (2017/02/28)
The invention provides a preparation method of cytarabine 5'-O-L-valine ester hydrochloride (structural formula 1) and an intermediate thereof. According to the invention, cytarabine (formula 5) is adopted as a raw material, and a one-step amino protection reaction is carried out, such that a substance represented by a structural formula 3 is obtained; the substance represented by the structural formula 3 and N'-tert-butoxycarbonyl-L-valine are subjected to a reaction with chloroformate or acyl chloride under the existence of alkali, or the substance represented by the structural formula 3 and N'-tert-butoxycarbonyl-L-valine salt are subjected to an esterification reaction under the effect of chloroformate or acyl chloride, such that a substance represented by a structural formula 2 is obtained; and protection group is removed under the effect of hydrogen chloride, such that the substance represented by the structural formula 1 is obtained. The method provided by the invention has the advantages of easy operation, simple post-treatment, no need of column chromatography purification, high selectivity, high reaction yield, and low cost. The method is suitable for industrialized productions.
TREATMENT OR PROPHYLAXIS OF PROLIFERATIVE CONDITIONS
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Page/Page column 63, (2010/11/17)
The invention relates to novel compounds for use in the treatment or prophylaxis of cancers and other proliferative conditions that are for example characterized by cells that express cytochrome P450 1B1 (CYP1B1) and allelic variants thereof. The invention also provides pharmaceutical compositions comprising one or more such compounds for use in medical therapy, for example in the treatment of prophylaxis of cancers or other proliferative conditions, as well as methods for treating cancers or other conditions in human or non-human animal patients. The invention also provides methods for identifying novel compounds for use in the treatment of prophylaxis of cancers and other proliferative conditions that are for example characterized by cells that express CYP1 B1 and allelic variants thereof. The invention also provides a method for determining the efficacy of a compound of the invention in treating cancer.
Synthesis and investigation of N4-substituted cytarabine derivatives as prodrugs.
Fadl,Hasegawa,Youssef,Farag,Omar,Kawaguchi
, p. 382 - 387 (2007/10/02)
Esters of Cytarabine-N4-carboxylates 2a-i and succinamates 3a-f were synthesized as prodrugs of cytarabine (Ara-C) with the aim of developing improved derivatives for oral or parentral administration. At pH 2 series 2 showed relative higher stability than 3, while both series of esters revealed matched stability at pH 7. All esters were susceptible to enzymatic hydrolysis by rat plasma and liver homogenate with half lives ranged from 0.14 h to 12 d, and showed improved stability against cytidine deaminase. A parabolic relation was shown between Kobs of enzymatic hydrolysis and Vw. All compounds are more lipophilic than the parent drug, Ara-C.
