19083-21-7

Upstream product

• 39824-26-5 6-chloro-9-(2,3-O-isopropylidene-β-D-ribofuranosyl)-9H-purine 
• 124-40-3 dimethyl amine 
• 77-76-9 2,2-dimethoxy-propane 
• 2620-62-4 N,N-dimethyladenosine 
• 2620-62-4 N⁶,N⁶-Dimethyladenosine 
• 67-64-1 acetone 
• 58-63-9 Inosine 
• 5987-73-5 2',3',5'-O-triacetyl-6-chloroinosine 
• 3181-38-2 2',3',5'-tri-O-acetylinosine 
• 2004-06-0 6-Chloropurine riboside 
• 109-83-1 (2-hydroxyethyl)(methyl)amine 
• 105499-44-3 2,3,5-tri-O-acetyl-α-D-ribofuranosyl chloride 
• 31199-61-8 (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(6-(dimethylamino)-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate 

Downstream Products

• 15087-42-0 5'-O-Benzoyl-N⁶,N⁶-dimethyladenosine 
• 1381763-89-8 1-(4-(tert-butyl)phenyl)-3-(3-((((2R,3S,4R,5R)-5-(6-(dimethylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)urea 
• 1381763-88-7 1-(4-(tert-butyl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(6-(dimethylamino)-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)propyl)urea 
• 362-75-4 2',3'-isopropylidene adenosine 
• 143995-02-2 N⁶-formyl-2',3'-O-isopropylideneadenosine 
• 143995-03-3 N⁶-formyl-2',3'-O-isopropylidene-N⁶-methyladenosine 
• 4566-77-2 ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-(methylamino)-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol 
• 15502-55-3 5'-O-Benzoyl-N⁶,N⁶-dimethyl-2'3'-O-isopropylideneadenosine 
• 74397-38-9 5'-O-Benzyl-N⁶,N⁶-dimethyladenosine 

Relevant academic research and scientific papers

Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues

Transient receptor potential melastatin-2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5′-diphosphoribose analogues were synthesized, and their activities and selectivity were evaluated. Whole-cell patch-clamp recordings were employed for screen and evaluation of synthesized compounds. Two compounds, 7i and 8a, were identified as TRPM2 inhibitors with IC50 of 5.7 and 5.4?μm, respectively. Both 7i and 8a inhibited TRPM2 current without affecting TRPM7, TRPM8, TRPV1 and TRPV3. These two TRPM2 inhibitors can serve as new pharmacological tools for further investigation and validation of TRPM2 channel as a drug target, and the summarized structure–activity relationship (SAR) may also provide insights into further improving existing inhibitors as potential lead compounds.

α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

ecto-5′-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor α,β-methylene-ADP (AOPCP, adenosine-5′-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N6-Monosubstitution was superior to symmetrical N6,N6-disubstitution. The most potent inhibitors were N6-(4-chlorobenzyl)- (10l, PSB-12441, Ki 7.23 nM), N6-phenylethyl- (10h, PSB-12425, Ki 8.04 nM), and N6-benzyl-adenosine-5′-O-[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, Ki 9.03 nM). Replacement of the 6-NH group in 10g by O (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 nM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nucleotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF

Disclosed are compounds, pharmaceutical compositions containing the compounds, and the uses of the compounds and compositions as modulators of histone methyltransferases, and for treating diseases influenced by modulation of histone methyltransferase activity.

Inhibition of siderophore biosynthesis in Mycobacterium tuberculosis with nucleoside bisubstrate analogues: Structure-activity relationships of the nucleobase domain of 5′-O-[N-(salicyl)sulfamoyl]adenosine

5′-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) is a prototype for a new class of antitubercular agents that inhibit the aryl acid adenylating enzyme (AAAE) known as MbtA involved in biosynthesis of the mycobactins. Herein, we report the structure-based design, synthesis, biochemical, and biological evaluation of a comprehensive and systematic series of analogues, exploring the structure-activity relationship of the purine nucleobase domain of Sal-AMS. Significantly, 2-phenyl-Sal-AMS derivative 26 exhibited exceptionally potent antitubercular activity with an MIC99 under iron-deficient conditions of 0.049 μM while the N-6-cyclopropyl-Sal-AMS 16 led to improved potency and to a 64-enhancement in activity under iron-deficient conditions relative to iron-replete conditions, a phenotype concordant with the designed mechanism of action. The most potent MbtA inhibitors disclosed here display in vitro antitubercular activity superior to most current first line TB drugs, and these compounds are also expected to be useful against a wide range of pathogens that require aryl-capped siderphores for virulence.

Antibacterial Agents

The invention provides compounds of formula (I) and salts thereof: R1-L-R2—B wherein R1, L, R2, and B have any of the values defined herein, as well as compositions comprising such compounds, and therapeutic methods comprising the administration of such compounds or salts. The compounds block siderophore production in bacteria and are useful as antibacterial agents.

The Prominent Effect of N6-Acyl Groups on the Reactivity of 9-Substituted Adenines: A New Method for the Chemical Modification of Adenines

The effect of various N6-substituents on the C(8)-hydrogen exchange of 9-substituted adenines has been estimated.The kinetic data clearly demonstrate that the N6-acyl groups significantly accelerate the C(8)-hydrogen exchange.This fa