Therapeutic Potential, Synthesis, Patent Evaluation and SAR Studies of Thieno[3,2-d]pyrimidine Derivatives: Recent Updates

Abstract

: Thieno[3,2-d]pyrimidine ring framework comprises a significant class of heterocyclics that serve as a promising platform showing different pharmacological activities. The interest in thieno[3,2-d]pyrimidine cores for pharmaceutical products makes this scaffold an exceptionally helpful building block for organic chemistry. This review presents current research on thieno[3,2-d]pyrimidines and elucidates their biological importance in anti-cancer, anti-infectious, anti-convulsant, anti-diabetic, CNS, and osteoporosis drug discoveries. Patents on the thieno[3,2-d]pyrimidines are also elaborated as a piece of useful information. Here we additionally focus on the synthesis of this vital ring and the discovery of new thieno[3,2-d]pyrimidines.

Inhibition of FLT3-ITD Kinase in Acute Myeloid Leukemia by New Imidazo[1,2-b]pyridazine Derivatives Identified by Scaffold Hopping

“…Trisubstituted purines were previously described as potent CDK and FLT3-ITD kinase inhibitors. − In order to explore this understudied chemical space and generate new active compounds, we designed new isosteric trisubstituted derivatives of several heterocyclic cores, including thieno­[3,2- d ]­pyrimidine, − pyrazolo­[1,5- a ]­pyrimidine, − imidazo­[4,5- b ]­pyridine, pyrido­[4,3- d ]­pyrimidine, and imidazo­[1,2- b ]­pyridazine , (Figure B). All of the prepared compounds were tested for their inhibitory activity against recombinant FLT3-ITD and CDK2/E.…”

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

“…Morpholine was added dropwise to the solution to obtain 16 . Cyclization of 16 with chloro-formamidine hydrochloride, formamide and acetonitrile afforded 17 , 18 and 19 , respectively, using reported methods [ 25 , 45 , 46 ]. Chlorination [ 47 ] of 17 – 19 with POCl 3 and pyridine in toluene afforded 20 – 22 in 68–75% yield.…”

Tandem [3+1+1+1] Heterocyclization of α‐Acyl Ketene Dithioacetals with Ammonia and Methanol: Rapid Assembly of Polysubstituted Pyrimidines

“…The privileged pyrimidine frameworks occupy a prominent role in natural products, agrochemicals, pharmaceuticals, supramolecules, and genetic and photophysical materials [1] . Especially their excellent biological and pharmacological activities including antibacterial, [2a,b] antitumor, [2c–f] antimalarial, [2g] anti‐inflammatory, [2h,i] and anticonvulsant [2j,k] etc, have led to the generation of numerous commercialized medicines such asvitamin B1, [3a] nimustine, [3b] voriconazole, [3c] ruxolitinib [3d] (Figure 1). Consequently, the new and efficient synthetic strategies are continuously demanded to acquire pyrimidine cores with rapid diversification.…”