157119-69-2

Upstream product

• 548942-89-8 5-nitro-1,3-dipropyl-6-styryluracil 
• 157119-86-3 5-nitro-1,3-dipropyl-6-styryl-1H-pyrimidine-2,4-dione 
• 7454-99-1 6-methyl-3-propyluracil 
• 157119-79-4 6-methyl-5-nitro-1,3-dipropyl-1H-pyrimidine-2,4-dione 
• 62899-00-7 6-methyl-1,3-dipropyluracil 

Relevant academic research and scientific papers

1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A2B adenosine receptor antagonists: Design, synthesis, structure-affinity and structure-selectivity relationships

A number of 1,3-dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines were prepared and evaluated as ligands of recombinant human adenosine receptors (hARs). Several 1,3-dipropyl derivatives endowed with nanomolar binding affinity at hA2B receptors, but poor selectivity over hA2A, hA1 and hA3 AR subtypes were identified. A comparison with the corresponding 7-OH- and 7,9-unsubstituted-deazaxanthines revealed that 9-OH-9-deazaxanthines are more potent hA2B ligands with lower partition coefficients and higher water solubility compared to the other two congeneric classes of deazaxanthines. An optimization of the para-substituent of the 8-phenyl ring of 9-OH-9-deazaxanthines led to the discovery of compound 38, which exhibited outstanding hA2B affinity (Ki = 1.0 nM), good selectivity over hA2A, hA1 and hA3 (selectivity indices = 100, 79 and 1290, respectively) and excellent antagonist potency in a functional assay on rat A2B (pA2B = 9.33).

New pyrrolopyrimidin-6-yl benzenesulfonamides: Potent A2B adenosine receptor antagonists

A new series of 4-(1,3-dialkyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6 -yl)benzenesulfonamides has been identified as potent A2B adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A2B, A1 and A3 adenosine receptors. 6-(4-{[4-(4-Bromobenzyl)piperazin-1-yl]sulfonyl}phenyl)-1,3-dimethyl-1H- pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (16) showed a high affinity for the A2B adenosine receptor (IC50 = 1 nM) and selectivity (A1: 183x; A3: 12660x). Synthesis and SAR of this novel class of compounds showing improved absorption properties is presented herein.

8-Substituted-9-deazaxanthines as adenosine receptor ligands: Design, synthesis and structure-affinity relationships at A2B

A number of 8-substituted-9-deazaxanthine derivatives (1,3-dialkyl-6- substituted-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-diones) were prepared and tested for their antagonistic activity at the recombinant human adenosine receptors, in particular at the A

Fast and highly efficient one-pot synthesis of 9-deazaxanthines

SnCl2 enables a direct, high-yield conversion of 5-nitro-1,3-dialkyl-6-styryl(furyl-, thienyl-vinyl)-uracils to 8-substituted-9-deazaxanthines under very mild experimental conditions. The method has a general applicability and it is compatible with the reactivity of the most common organic functional groups. In slightly experimental different conditions, it allows a high-yield and fast (5 min) preparation of pure 7-N-hydroxy-9-deazaxanthines.

Synthesis and structure-activity relationships of deazaxanthines: Analogs of potent A1- and A2-adenosine receptor antagonists

A set of 22 9-deazaxanthines (pyrrolo[3,2-d]pyrimidine-2,4-diones) and three 7-deazaxanthines (pyrrolo[2,3-d]pyrimidine-2,4-diones) with various substituents in the 1-, 3-, 7- or 9-, and 8-positions was synthesized and investigated in A1 and A2a adenosine receptor binding assays at rat brain cortical membranes and rat brain striatal membranes, respectively. 9- Deazaxanthines showed structure-activity relationships that were similar to those of xanthines. They were about equipotent to the corresponding xanthines at A2a adenosine receptors. 9-Deazaxanthines were generally at least 1-3- fold more potent than xanthines at A1 receptors and therefore exhibited higher A1 selectivities compared to the xanthines. 1,3-Dimethyl-8-(2- naphthyl)-9-deazaxanthine (19e) showed high affinity (K(i) = 26 nM) and selectivity for A1 adenosine receptors. A hydroxyl function at N7 of 9- deazaxanthines was unfavorable for A1 and A2a receptor binding. 7- Deazaxanthines were considerably less potent compared to xanthines and to 9- deazaxanthines at both receptor subtypes.