35970-78-6

Upstream product

• 100-52-7 benzaldehyde 
• 98-80-6 phenylboronic acid 
• 56844-40-7 6-bromothieno[2,3-d]pyrimidin-4(3H)-one 
• 14080-50-3 thieno[2,3-d]pyrimidin-4(3H)one 
• 122-78-1 phenylacetaldehyde 
• 4815-34-3 ethyl 2-amino-5-phenylthiophene-3-carboxylate 
• 77287-34-4 formamide 

Downstream Products

• 35970-79-7 4-chloro-6-phenylthieno[2,3-d]pyrimidine 
• 718615-92-0 4-iodo-6-phenylthieno[2,3-d]pyrimidine 
• 35970-80-0 4-hydrazino-6-phenyl-thieno[2,3-d]pyrimidine 
• 35970-81-1 8-phenyl-thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine 
• 315685-01-9 C₁₂H₈N₂S₂ 
• 457641-02-0 C₁₆H₁₄N₂O₂S₂ 
• 457641-35-9 [(6-phenylthieno[2,3-d]pyrimidin-4-yl)thio]acetic acid 
• 1610771-88-4 (((6-phenylthieno[2,3-d]pyrimidin-4-yl)amino)methyl)phosphonic acid 

Relevant academic research and scientific papers

The Discovery and Development of Thienopyrimidines as Inhibitors of Helicobacter pylori That Act through Inhibition of the Respiratory Complex i

The successful treatment of Helicobacter pylori infections is becoming increasingly difficult due to the rise of resistance against current broad spectrum triple therapy regimens. In the search for narrow-spectrum agents against H. pylori, a high-throughp

Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor

We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs that retain robust negative cooperativity, such as 3. Herein, we report the synthesis and functional profiling of analogues of 3, placing specific emphasis on examining secondary and tertiary amino substituents at the 4-position, combined with a range of substituents at the 5/6-positions (e.g. aromatic/aliphatic carbocycles). We identify analogues with diverse pharmacology at the D2R including NAMs with sub-μM affinity (9h) and, surprisingly, low efficacy partial agonists (9d and 9i).

Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2- d]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors

The clinical evidence for the success of tyrosine kinase inhibitors in combination with microtubule-targeting agents prompted us to design and develop single agents that possess both epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitory properties. A series of 6-aryl/heteroaryl-4-(3′,4′,5′-trimethoxyanilino)thieno[3,2-d]pyrimidine derivatives were discovered as novel dual tubulin polymerization and EGFR kinase inhibitors. The 4-(3′,4′,5′-trimethoxyanilino)-6-(p-tolyl)thieno[3,2-d]pyrimidine derivative 6g was the most potent compound of the series as an antiproliferative agent, with half-maximal inhibitory concentration (IC50) values in the single- or double-digit nanomolar range. Compound 6g bound to tubulin in the colchicine site and inhibited tubulin assembly with an IC50 value of 0.71 μM, and 6g inhibited EGFR activity with an IC50 value of 30 nM. Our data suggested that the excellent in vitro and in vivo profile of 6g may be derived from its dual inhibition of tubulin polymerization and EGFR kinase.

Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines

An extension of our previous research work has resulted in a number of new ATP-competitive CK2 inhibitors that have been identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in the course of the research are 3-(5-p-tolyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5e (NHTP23, IC50 = 0.01 μM), 3-(5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5g (NHTP25, IC50 = 0.065 μM) and 3-(6-methyl-5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5n (NHTP33, IC50 = 0.008 μM). Structure-activity relationships of the tested 4-aminothieno[2,3-d]pyrimidine derivatives have been studied and their binding mode with ATP-acceptor site of CK2 has been proposed. A negative effect of intramolecular hydrogen bonding in the compounds' structure is discussed.

Route selection in the synthesis of C-4 and C-6 substituted thienopyrimidines

Three different routes have been investigated for the preparation of 6-aryl-N-(1-arylethyl)thienopyrimidin-4-amines. First the possibilities of selective Suzuki reactions on 6-bromo-4-chlorothienopyrimidine were investigated. The preference for mono arylation at C-6 could be increased, in the case of Pd(PPh3)4 catalysis, by reducing the water content of the reaction, or by using less electron rich Pd-ligands. The highest selectivity was obtained with Pd(OAc)2 or Pd2(dba) 3, while reactions with the more electron rich Pd(PPh 3)4 and especially XPhos gave a lower mono- to dicoupled product ratio. Secondly, two alternative strategies avoiding this selectivity issue were tested. Suzuki reaction on C-6 of 6-bromothienopyrimidin-4(3H)-one (three examples) proceeded in 70-89% yield using Pd(PPh3)4 in dioxane/water. Similar conditions on 4-amino-6-bromo-thienopyrimidine (eight examples) gave 67-95% yield. The reaction could be performed with boronic acids containing nonprotected phenolic groups in the ortho, meta and para positions. By prolonging the reaction time, coupling with sterically crowded arylboronic acids was also efficient. Diarylation of 6-bromo-4-chlorothienopyrimidine gave the corresponding 4,6-diarylated derivatives in 71-80% yield depending on the nature of the arylboronic acid.

Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin- 4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2

A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC 50 values are 0.1 μM and 0.125 μM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2.

4-Metalated condensed pyrimidines: Their preparation and reaction with aldehydes under barbier-type conditions

Equation presented. The organometallic intermediate obtained from halogen-metal exchanges of 4-iodo-6-phenylthieno[2,3-d]pyrimidine under Barbier-type conditions was reacted with aldehydes to form the corresponding alcohols in moderate yields. The reaction involving an organolithium intermediate proceeded only at low temperature, whereas the reaction involving a magnesium ate intermediate also proceeded at room temperature. A crystal structure confirms that the expected constitutional alcohol isomer is formed, where no migration has taken place. The conditions were also suitable for 9-benzyl-6-iodopurine.