55726-45-9

Usage

InChI:InChI=1/C25H43N3O6/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-21(30)26-20-16-17-28(25(33)27-20)24-23(32)22(31)19(18-29)34-24/h16-17,19,22-24,29,31-32H,2-15,18H2,1H3,(H,26,27,30,33)

Upstream product

• 623-65-4 palmitic anhydride 
• 147-94-4 arabinosyl cytosine 
• 120246-99-3 palmitoyl ethyl carbonate 
• 57-10-3 1-hexadecylcarboxylic acid 

Downstream Products

• 176776-97-9 Hexadecanoic acid 2-{(2-chloro-phenoxy)-[(2R,3S,4S,5R)-5-(4-hexadecanoylamino-2-oxo-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-phosphoryloxy}-1-hexadecanoyloxymethyl-ethyl ester 
• 176683-46-8 Phosphoric acid 2,3-bis-octadecyloxy-propyl ester 2-chloro-phenyl ester (2R,3S,4S,5R)-5-(4-hexadecanoylamino-2-oxo-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester 

Relevant academic research and scientific papers

Rational design of a new cytarabine-based prodrug for highly efficient oral delivery of cytarabine

Because of the drawbacks of cytarabine (Ara-C) such as poor lipid solubility, deamination inactivation and low oral bioavailability limiting its application by oral administration, herein we propose a novel amphiphilic low molecular weight cytarabine prodrug (PA-Ara) by conjugating palmitic acid (PA) to Ara-C, making it possible to avoid the deamination inactivation by protecting the active 4-amino, as well as improving lipid solubility. Thanks to the rational design, the oil/water partition coefficient (P) of PA-Ara was improved tremendously compared with Ara-C, and the PA-Ara conjugation was stable enough in artificial digestive juice, ensuring that most molecules could be absorbed in the form of the prodrug. Results from an MTT assay conducted to measure the cytotoxicity of Ara-C and PA-Ara to HL60 (acute myeloblastic leukemia cell line) and K562 cells (chronic granulocytic leukemia cell line) showed that PA-Ara had significantly stronger antiproliferation activities than Ara-C. Significantly, we firstly compared the bioavailability of the oral fatty acid chain modified cytarabine prodrug preparation with injection and the relative bioavailability was up to 61.77% for our PA-Ara, which was much superior to that of oral Ara-C solution (3.23%). Overall, these findings make it clear that the PA-Ara suspension has the potential to be a promising new cytarabine oral preparation for leukemia therapy.

Amphipathic small molecular prodrug of cytosine arabinoside and preparation method and application thereof

The invention discloses an amphipathic small molecular prodrug of cytosine arabinoside and a preparation method and an application thereof. The novel amphipathic small molecular prodrug of cytosine arabinoside palmitic-cytosine arabinoside is synthesized by covalently binding biocompatible palmitic acid as a lyophobic material with cytosine arabinoside. Through a simple nano-settlement process, the prodrug can be self-assembled in water to form a nano spiral aggregate which is centrifugally dried to obtain a nano oral administration preparation which is stable in property. An in vivo pharmacokinetical result of a mouse shows that the prodrug nano oral preparation can prolong the plasma half-life of cytosine arabinoside and is good in bioavailability. The prodrug oral preparation is high in drug load, simple and economical in preparation process, can be produced in batches, is small in toxicity and good in safety and provides a wide application prospect for oral administration forms of cytosine arabinoside.

Lipophilic 5'-(Alkyl phosphate) Esters of 1-β-D-Arabinofuranosylcytosine and Its N4-Acyl and 2,2'-Anhydro-3'-O-acyl Derivatives as Potential Prodrugs

Lipophilic 5'-(alkyl phosphate) esters of 1-β-D-arabinofuranosylcytosine (ara-C) and several N4-acyl and 3'-O-acyl-2,2'-anhydro derivatives of ara-C were synthesized as potential prodrugs of ara-C 5'-monophosphate (ara-CMP).Alkylphosphorylation of ara-C, N4-palmitoyl-ara-C, and N4-stearoyl-ara-C was achieved in a single continuous operation by allowing the nucleoside to react with POCl3 in trimethyl or triethyl phosphate and adding the appropriate anhydrous alcohol directly to the intermediate phosphorodichloridate without isolation.Similar reaction of cytidine yielded cytidine 5'-(alkyl phosphate) esters, which on treatment with myristoyl or palmitoyl chloride in the presence of boron trifluoride gave 3'-O-acyl-2,2'-anhydro-ara-C 5'-(alkyl phosphate) esters.Ara-C 5'-(n-butyl phosphate) (1b), N4-palmitoyl-ara-C 5'-(n-butyl phosphate) (1h), and 2,2'-anhydro-3'-O-palmitoyl-ara-C 5'-(n-butyl phosphate) (2h) were tested against L1210/ara-C leukemia in mice in the hope that this kinase-deficient tumor would respond to treatment with these "prephosphorylated" derivatives, but no activity was observed.Of the simple 5'-(alkyl phosphate) esters tested in culture against L1210 leukemic cells, only ara-C 5'-(glyceryl phosphate) (1g) showed toxicity comparable to ara-CMP (ID50 = 0.35 and 0.65 μM, respectively), suggesting that β-hydroxyalkyl phosphate esters may be worthwhile to examine further as prodrugs of ara-CMP.

N4 -acylarabinonucleosides

An N4 -acyl-1-β-D-arabinofuranosylcytosine having the following formula SPC1 Wherein R is an aliphatic acyl group having 3 to 35 carbon atoms. The compounds of this invention are useful as a cancer chemotherapeutic agent for controlling tumors, e.g., in mice, an insecticide, and a fungicidal surface active agent.