Category: 1019206-88-2

Zheng, Deqiang published the artcileSynthesis of regorafenib, Synthetic Route of 1019206-88-2, the publication is Zhongguo Yiyao Gongye Zazhi (2016), 47(5), 528-530, database is CAplus.

Regorafenib was synthesized from 3-fluoro-4-nitrophenol (2) via reduction nitro group, nucleophilic substitution with N-methyl-4-chloropyridine-2-carboxamide (5), condensation with 4-chloro-3-(trifluoromethyl) Ph isocyanate (8), and then recrystallization by salt formation and neutralization with an overall yield of 63.8% (based on 2).

Zhongguo Yiyao Gongye Zazhi published new progress about 1019206-88-2. 1019206-88-2 belongs to amides-buliding-blocks, auxiliary class Protein Tyrosine Kinase/RTK,VEGFR, name is 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide hydrate, and the molecular formula is C15H14O3, Synthetic Route of 1019206-88-2.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Mueller, Martin published the artcileImpact of co-administered stabilizers on the biopharmaceutical performance of regorafenib amorphous solid dispersions, Quality Control of 1019206-88-2, the publication is European Journal of Pharmaceutics and Biopharmaceutics (2021), 189-199, database is CAplus and MEDLINE.

Poor solubility of drug candidates is a well-known and thoroughly studied challenge in the development of oral dosage forms. One important approach to tackle this challenge is the formulation as an amorphous solid dispersion (ASD). To reach the desired biopharmaceutical improvement a high supersaturation has to be reached quickly and then be conserved long enough for absorption to take place. In the presented study, various formulations of regorafenib have been produced and characterized in biorelevant in-vitro experiments Povidone-based formulations, which are equivalent to the marketed product Stivarga, showed a fast drug release but limited stability and robustness after that. In contrast, HPMCAS-based formulations exhibited excellent stability of the supersaturated solution, but unacceptably slow drug release. The attempt to combine the desired attributes of both formulations by producing a ternary ASD failed. Only co-administration of HPMCAS as an external stabilizer to the rapidly releasing Povidone-based ASDs led to the desired dissolution profile and high robustness. This optimized formulation was tested in a pharmacokinetic animal model using Wistar rats. Despite the promising in-vitro results, the new formulation did not perform better in the animal model. No differences in AUC could be detected when compared to the conventional (marketed) formulation. These data represent to first in-vivo study of the new concept of external stabilization of ASDs. Subsequent in-vitro studies revealed that temporary exposure of the ASD to gastric medium had a significant and long-lasting effect on the dissolution performance and externally administered stabilizer could not prevent this sufficiently. By applying the co-administered HPMCAS as an enteric coating onto Stivarga tablets, a new bi-functional approach was realized. This approach achieved the desired tailoring of the dissolution profile and high robustness against gastric medium as well as against seeding.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about 1019206-88-2. 1019206-88-2 belongs to amides-buliding-blocks, auxiliary class Protein Tyrosine Kinase/RTK,VEGFR, name is 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide hydrate, and the molecular formula is C21H17ClF4N4O4, Quality Control of 1019206-88-2.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Fukunishi, Yoshifumi published the artcilePrediction of Synthetic Accessibility Based on Commercially Available Compound Databases, COA of Formula: C21H17ClF4N4O4, the publication is Journal of Chemical Information and Modeling (2014), 54(12), 3259-3267, database is CAplus and MEDLINE.

A compound’s synthetic accessibility (SA) is an important aspect of drug design, since in some cases computer-designed compounds cannot be synthesized. There have been several reports on SA prediction, most of which have focused on the difficulties of synthetic reactions based on retro-synthesis analyses, reaction databases and the availability of starting materials. The authors developed a new method of predicting SA using com. available compound databases and mol. descriptors. SA was estimated from the probability of existence of substructures consisting of the compound in question, the number of symmetry atoms, the graph complexity, and the number of chiral centers of the compound The probabilities of the existence of given substructures were estimated based on a compound library. The predicted SA results reproduced the expert manual assessments with a Pearson correlation coefficient of 0.56. Since the authors method required a compound database and not a reaction database, it should be easy to customize the prediction for compound vendors. The correlation between the sales price of approved drugs and the SA values was also examined and weak. The price most likely depends on the total cost of development and other factors.

Journal of Chemical Information and Modeling published new progress about 1019206-88-2. 1019206-88-2 belongs to amides-buliding-blocks, auxiliary class Protein Tyrosine Kinase/RTK,VEGFR, name is 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide hydrate, and the molecular formula is C21H17ClF4N4O4, COA of Formula: C21H17ClF4N4O4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics