Injectable Hydrogel for Sustained Protein Release by Salt‐Induced Association of Hyaluronic Acid Nanogel

A hyaluronic acid‐based anionic nanogel formed by self‐assembly of cholesteryl‐group‐bearing HA is designed for protein delivery. The HA nanogel spontaneously binds various types of proteins without denaturation, such as recombinant human growth hormone, erythropoietin, exendin‐4, and lysozyme. The HA nanogel shows unique colloidal properties, in particular that an injectable hydrogel is formed by salt‐induced association of the HA nanogel. A pharmacokinetic study in rats shows that an in situ gel formulation, prepared by simply mixing rhGH and HA nanogel in phosphate buffer, maintains plasma rhGH levels within a narrow range over one week. Therefore, HA nanogels offer a simple method for easy formulation of therapeutic proteins and are effective for sustained protein release systems.

     

Synthesis of a novel diazepine

A novel pyrrolopyridodiazepine ring system was synthesized from methyl 2‐methyl nicotinate.     

Transformations of phenylhydrazones of 5‐acyl‐1,2,4‐triazines to pyrazolo[4,3‐e][1,2,4]triazines or 4‐cyanopyrazole

A simple and high yielding preparation of pyrazolo[4,3‐e][1,2,4]triazines and 4‐cyano‐3‐methyl‐1‐phenylpyrazole derivatives from corresponding phenylhydrazones of 5‐acyl‐1,2,4‐triazines by melt under acidic medium and by thermal heating, respectively.     

Phosphomolybdic acid catalyzed facile one‐pot synthesis of 2,4,5‐triaryl‐1H‐imidazoles from benzil and aromatic aldehydes

A facile one‐pot synthesis of 2,4,5‐triaryl‐1H‐imidazoles with better yields and shorter reaction time from the condensation of benzil, ammonium acetate and aromatic aldehydes using the catalyst phosphomolybdic acid is described     

Simple and efficient one‐pot synthesis of 3,4‐dihydro‐2‐pyridones via solid‐supported Bi(III)nitrate catalyzed double michael addition‐azaannulation

4‐Aryl‐5‐carboethoxy‐6‐methyl‐2,3‐dihydro‐2‐pyridones were obtained, in high yield, by heating ternary mixtures of appropriate aldehydes, ethylacetoacetate and compounds possessing NH₂‐C=X functionality, in presence of immobilized Bi(III)nitrate and co‐catalyst Zn(II)chloride, under solventless conditions. The reaction proceeds smoothly at 140±5°C and seems to involve double Michael addition‐azaannulation.