Heterocyclic steroids: Synthetic routes and biological characteristics of steroidal fused bicyclic pyrimidines

Abstract

Natural steroids are characterized as a vital class of compounds, a type of secondary metabolites and components of cell membranes that widely accessible in plants or animals displayed significant pharmacological and varied biological properties. The present study aims to highlight the conveyed researches of synthetic routes adopted to obtain the various structures of steroidal fused bicyclic pyrimidines with substantial biological and pharmaceutical importance. The topic was discussed in light of the synthesis of fused [6 + 5] bicyclic systems, fused [6 + 6] bicyclic systems, binary heterocycles, and biological applications. In detail, the various synthetic strategies for the construction of steroids fused to bicyclic pyrazolopyrimidines, thiazolopyrimidines, triazolopyrimidines, pyridopyrimidines, pyranopyrimidines, and binary pyrimidines were discussed. Heterocyclic steroids of this class of compounds demonstrated potent anticancer, anti‐proliferative, anti‐neuro‐inflammatory, anti‐inflammatory, and anti‐ulcer activities. It was perceived that the synthetic steroids of such bicyclic pyrimidine scaffolds are fused into the steroid basic skeleton is essential for the potent bioactivities.

Insights into the recent progress in the medicinal chemistry of pyranopyrimidine analogs

“…Thus, this study has been undertaken as a persistence of our previous programs and studies on highlighting the chemistry of heterocyclic compounds with miscellaneous biological activities and their significance in the fields of medicinal and pharmaceutical chemistry. [52][53][54][55][56][57][58][59] Our program deals with highlighting and exploring the prosperous medicinal chemistry of pyranopyrimidine compounds, particularly pyranoij2,3-d]pyrimidines, in the last five years. The topic of this research is an extension of our previous study that is interesting to highlight the recent methods and progress in the multicomponent synthesis of heterocycleincorporated pyranoij2,3-d]pyrimidine motif under different conditions.…”

Design, Synthesis and Anticancer Activity of Novel Steroidal Derivatives with D‐Ring Fused or Substituted N‐Heterocyclic Systems

“…[1][2][3][4] During the last decades, the construction of steroidal N-heterocycles widely to pay attention since they had great research potential for the treatment of a great deal of diseases, especially anticancer activity, [5] e. g., pyridine, benzimidazole, imidazole, and triazole fused with A-ring or substituted with D-ring in the steroid skeletons. [6][7][8] At present, steroidal derivatives with D-ring fused N-heterocycle, abiraterone and galeterone have been used in the clinic for the treatment of prostate cancers, [6,9,10] while steroidal derivatives with D-ring substituted N-heterocycle, 1,3,5 (10)-estratrien [17,16-c]pyrazole was also a potent inhibitor of 17β-hydroxysteroid dehydrogenases (17β-HSD) with IC 50 values of 530 nM against human breast cancer T47-D cells [11,12] (Figure 1), suggesting the D-ring fused or substituted N-heterocyclic system possibly was a promising structural modification strategy to improve antitumor activity for steroids. Even though numerous steroidal N-heterocycles with pyrazole, isoxazole, pyridine, pyran, pyrrole and pyrimidine rings had been successful synthesized by various synthetic strategies in the literature, [13 -20] the structure-activity relationship (SAR) of the different Nheterocyclic systems located to the D-ring were seldom reported and deserved further study.…”

“…A great number of structural modification for steroidal A‐ and D‐ring had been proved to enhance or give them a lot of new pharmacological activities [1–4] . During the last decades, the construction of steroidal N‐heterocycles widely to pay attention since they had great research potential for the treatment of a great deal of diseases, especially anticancer activity, [5] e. g., pyridine, benzimidazole, imidazole, and triazole fused with A‐ring or substituted with D‐ring in the steroid skeletons [6–8] . At present, steroidal derivatives with D‐ring fused N‐heterocycle, abiraterone and galeterone have been used in the clinic for the treatment of prostate cancers, [6,9,10] while steroidal derivatives with D‐ring substituted N‐heterocycle, 1,3,5(10)‐estratrien[17,16‐c]pyrazole was also a potent inhibitor of 17 β ‐hydroxysteroid dehydrogenases (17 β ‐HSD) with IC 50 values of 530 nM against human breast cancer T47‐D cells [11,12] ( Figure 1), suggesting the D‐ring fused or substituted N‐heterocyclic system possibly was a promising structural modification strategy to improve antitumor activity for steroids.…”

Synthesis and characterization of steroidal, anellated aminothiophenes by Gewald reaction

“…Heterocyclic steroids demonstrated potent bioactivity due to the incorporation of a fused heterocyclic ring into the steroid skeleton 1 . Many routes have been devised for their synthesis [1][2][3][4] .…”