Synthesis and evaluation of novel spiro derivatives for pyrrolopyrimidines as anti-hyperglycemia promising compounds

Abstract

Pyrrolopyrimidin-4-ylidene-malononitriles IIa–d were prepared as important intermediates for preparation of a new series of spiro-pyrrolopyrimidines. These intermediates undergo cyclisation via reaction with acetylacetone, guanidine hydrochloride or hydrazine hydrate. Elemental and spectroscopic evidences for the structures of these compounds are presented. The final compounds have been monitored for in vivo anti-hyperglycemic activity, compared with Amaryl as standard drug. Among 12 tested compounds, both spiro (pyrano IIIb and pyrazlo Va) derivatives exhibit promising anti-hyperglycemic activity.

Antioxidant spiropharanone, an undescribed variant of trans ‐decalin spiro‐ γ ‐lactone, from pharaoh cuttlefish Sepia pharaonis : Twin inhibitors of inflammatory 5‐lipoxygenase and serine protease dipeptidyl peptidase‐4

“…Earlier report of literature established the anti-inflammatory activity with effects on NO production in the LPS-induced RAW264.7 cell lines of the compounds with spirocyclic motifs in fusion with a furan ring (An et al, 2016). Oxygenated spiro undecane compounds extracted from the marine macroalga Gracilaria salicornia exhib- the key reasons of promising pharamacological activities including anti-hyperglycemia (Fatahala et al, 2018;Liu et al, 2019).…”

“…Over the past few decades, spiro-based heterocyclic systems gained considerable attention among the scientific community owing to their structural diversity and pharmacological activities (Zheng et al, 2014). Among the spirocyclic frameworks, the natural products with spirolactone moieties were extensively studied for their pharmacological profiling, particularly with regard to antiinflammatory, anti-proliferative, and anti-hyperglycemic activities (Fatahala et al, 2018;Liu et al, 2019). The asymmetric nature of spiro carbon in the spiro-based compounds coupled with superior conformational rigidity and flexible balance along with their structural novelty made them important candidates for pharmacophore discovery (Chupakhin et al, 2019).…”

Design, Synthesis, in Vitro, and in Silico Evaluations of 1,3,4‐Oxadiazole Derivatives Linked to the Pyrrolo[2,3‐d]pyrimidine Moieties as Potent Antimicrobial Targets

“…[24] The biological activities of pyrrolo-pyrimidine rings, which bear similarities to purines and pyrimidines ring, are known to be varied. These activities include anticancer, [25] antiviral, [26] enzyme inhibitors, [27] antimicrobial, [28] antifungal, [29] antibiotics, [30] and anti-diabetic, [31] anti-folates, [32] anti-inflammatory, [33] anti-allergic properties. [34] Many FDA-approved medications, such as ribociclib, [35] Ruxolitinib, Tofacitinib, [36] and Baricitinib, [37] are pyrrole-pyrimidine corecontaining medicines that work by inhibiting tyrosine kinase, Similar to As illustrated in Figure 1, pemetrexed is a chemotherapeutic medication used as an antifolate [38] and for the treatment of lung cancer with non-small cells.…”

Design, synthesis, in vitro anticancer, molecular docking and SAR studies of new series of pyrrolo[2,3-d]pyrimidine derivatives

“…The pyrrolo[2,3- d ]pyrimidine derivatives have an important place amongst the pyrrolopyrimidine compounds with various biological properties such as antibacterial [ 17 ], anti-diabetic agents [ 18 , 19 ], antiviral [ 20 , 21 ], anti-inflammatory [ 22 , 23 ], anti-hypertensive activity [ 24 ], anti-protozoal activity [ 25 ], and exhibited strong anticancer activity that serves as an efficient tool for DNA interaction [ 4 , 16 , 26 , 27 ].…”