Two steps involved in the synthesis of the aceclofenac prodrug.

Results: In vitro chemical hydrolysis profiles revealed that the synthesized amino acid derivative of famotidine was chemically stable in Simulated Gastric fluid pH 1.2 and Simulated Intestinal Fluid pH 7.4. Decrease in Log P value,-0.39 of amino acid prodrug compared to-0.60 of famotidine was observed.

Step-2: Synthesis of prodrug (2)



In conclusion, the synthesized prodrug had increased solubility, synergistic antiinflammatory and antiarthritic activity with lower toxicity and less ulcerogenic activity than the parent drug EC. Thus, this prodrug approach solves not only the formulation problem of EC (lower aqueous solubility, BCS class II drug) but also reduces gastric adverse effects.

Pandey, et al.: Mutual Prodrug Synthesis of Etodolac and Glucosamine

The synthesized prodrug along with EC was evaluated for analgesic, antiinflammatory, ulcerogenic, antiarthritic activity, and histopathology study. reports result of pharmacological screenings. In analgesic study, significant reduction in number of writhes were observed after treatment with EC and EC-GLU. The result indicates initially (after 2 h of administration) advantage of EC over EC-GLU but after 3 h equimolar dose of EC-GLU to EC has better analgesic activity. It may be due to stability of prodrug in gastric pH. The antiinflammatory activities after 6 h oral dosing of EC-GLU and EC shows inhibition of edema 70.1 and 81.9%. GLU has antiinflammatory property apart from antiarthritic activity[], responsible for synergistic effect on percentage inhibition of edema. EC-GLU shows better antiarthritic activity with respect to EC on 21st day. Value for ulcerogenic index shows notable difference between EC-GLU and EC. The minimized ulcerogenic index of prodrug might be due to inhibition of direct contact of carboxyl group of the drug to the gastric mucosa, which is mainly responsible for the damage. It is also due to negligible hydrolysis in stomach (pH 1.2) region as well.

Synthesis and evaluation of mutual prodrugs of …

Physical properties of synthesized prodrug, viz., yields, color, odor, aqueous solubility, Rf, Rm and melting point were observed. Solubility of 10 mg of prodrug was checked in demineralized water, methanol, phosphate buffer saline (PBS, pH 6.8) and methanol:PBS at pH 6.8 (80:20) at 37±10° in glass test tubes. Test tube is gently shaken and solubility was observed. In case of any observed insoluble fraction, the known amount of solvent was further added to ascertain the solubility of the compound. The synthesized prodrug was subjected to thin layer chromatography in order to check confirmation of product and their purity. The prepared plates of silica gel G adsorbents were dried and activated. The solvent system methanol:dichloromethane:benzene (4:1.5:0.5), visualizing agent ninhydrin was used. A dark pink spot on heating at 121° for 2-3 min in day light observed for Rf and Rm value calculation. Further confirmation and purity of compound checked on Qualisil Gold C18 column injecting on HPLC (LC 2010HT liquid chromatograph, Shimadzu, Japan). The melting point of the drug and synthesized prodrug was determined by capillary fusion method, by using calibrated thermometer and melting point apparatus (S. M. Scientific Instruments Pvt. Ltd., New Delhi). The λmax was determined at double beam UV/Vis spectrophotometer (UV-1700 Pharmspec, Shimadzu, Japan) by using software UV probe ver 2.33. Partition coefficient was determined in n-octanol/phosphate buffer of pH 7.4. The elemental analysis of EC-GLU was performed in Central Drug Research Institute, Lucknow, India, using Carlo-Erba Model 1108 Analyzer. It was carried out to find the percentage of C, H, and N in the prodrug. The IR spectra of the compounds were obtained on Spectrum two (FTIR spectormeter, Perkin Elmer, USA) by using software spectrum ver 10.3.02. The 1H NMR and mass analysis of the EC and EC-GLU were done on NMR spectrophotometer (Jeol) at 300 MHz using CDCl3 as solvent and on FAB mass spectrometer (Jeol S×102/DA-6000 mass spectrometer at IIT, Kanpur, India).

Abstract LB-199: SN38-dextran prodrug synthesis and …

N2 - The original synthesis of combretastatin A-2 (1a) was modified to provide an efficient scale-up procedure for obtaining this antineoplastic stilbene. Subsequent conversion to a useful prodrug was accomplished by phosphorylation employing in situ formation of dibenzylchlorophosphite followed by cleavage of the benzyl ester protective groups with bromotrimethylsilane to afford the phosphoric acid intermediate 11. The latter was immediately treated with sodium methoxide to complete a practical route to the disodium phosphate prodrug (2a). The phosphoric acid precursor (11) of phosphate 2a was employed in a parallel series of reactions to produce a selection of metal and ammonium cation prodrug candidates. Each of the phosphate salts (2a-q) was evaluated with respect to relative solubility behavior, cancer cell growth inhibition and antimicrobial activity.

Prodrug-based design, synthesis, and biological …

Owing to its sparingly soluble properties, the potential anticancer drug pancratistatin (1) resisted conventional drug formulation procedures and the synthesis of a water-soluble prodrug became necessary. That important objective for further pre-clinical development was met by devising a route to a disodium phosphate derivative (5). The key step in the synthesis of the phenolic phosphate was phosphorylation of 1,2,3,4-tetraacetoxy-pancratistatin (2) with dibenzyloxy(N,N-diisopropylamido)-phosphine. Subsequent oxidation with m-chloroperbenzoic acid afforded phosphate 4a. Hydrogenolysis of the benzyl esters followed by base-catalysed hydrolysis of the acetate groups led to the water-soluble prodrug 5 in high yield.