69205-79-4

Usage

Uses

Used in Pharmaceutical Industry:
3H-Pyrrolo[2,3-d]pyrimidine-5-carbonitrile, 2-amino-4,7-dihydro-4-oxois used as a reagent for the development of antiparasitic agents targeting pteridine reductase 1. Its application is crucial in the structure-based design and synthesis of pyrrolopyrimidines, which are potential therapeutic agents against parasitic infections. 3H-Pyrrolo[2,3-d]pyrimidine-5-carbonitrile, 2-amino-4,7-dihydro-4-oxoplays a significant role in advancing research and drug development for treating parasitic diseases.

InChI:InChI=1/C7H5N5O/c8-1-3-2-10-5-4(3)6(13)12-7(9)11-5/h2H,(H4,9,10,11,12,13)

Upstream product

• 74511-37-8 Acetic acid 2-acetylamino-5-cyano-4-oxo-3,4-dihydro-pyrrolo[2,3-d]pyrimidin-7-ylmethyl ester 
• 100643-27-4 2,6-diamino-3H-pyrimidin-4-one 
• 53106-70-0 2-chloro-2-formylacetonitrile 
• 107-31-3 Methyl formate 
• 107-14-2 chloroacetonitrile 
• 56-06-4 2,6-diaminopyrimidin-4-ol 
• 62805-58-7 3,7-Bis-methoxymethyl-5-methyl-2-methylsulfanyl-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one 
• 74511-36-7 2-Amino-3,7-bis-methoxymethyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile 
• 62805-57-6 N-(3,7-Bis-methoxymethyl-5-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-acetamide 
• 74511-33-4 7-hydroxymethyl-7-deazaguanine 
• 74511-34-5 N-(5-Formyl-3,7-bis-methoxymethyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-acetamide 
• 74511-35-6 N-[5-(Hydroxyimino-methyl)-3,7-bis-methoxymethyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]-acetamide 
• 74511-32-3 7-hydroxymethyl-8-bromodeazaguanine 
• 74511-29-8 N-Acetyl-N-(3,7-bis-methoxymethyl-5-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-acetamide 

Downstream Products

• 124738-81-4 2-amino-4-chloro-5-cyanopyrrolo<2,3-d>pyrimidine 
• 1019853-64-5 4,7-dihydro-4-oxo-2-[(triphenylmethyl)amino]-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile 
• 171624-11-6 7-formyl-7-deazaguanine 

Relevant academic research and scientific papers

Synthesis of azide congeners of preQ1 as potential substrates for tRNA guanine transglycosylase

PreQ1 (2) is a precursor of queuine (1) that in eubacteria is incorporated into transfer RNA (tRNA) by tRNA guanine transglycosylase (TGT) before being further elaborated into queuine. The queuine modification is unusual and occurs across all eukaryotes and eubacteria with few exceptions, but its function remains unclear. As the modified nucleotide occurs through incorporation of a specially synthesized nucleotide instead of via modification of a genetically encoded base, a study of the sites of modification by prepared probes is possible. We report the synthesis of two novel azide congeners (3,4) of preQ1 for this purpose. The evaluation of their interaction with TGT shows that both probes act as weak competitive inhibitors of guanine exchange of guanine(34) tRNATyr with a Ki of ~70 μM. However, we could not show that these are substrates for TGT-catalyzed incorporation into tRNA. We believe the reason for this is a marked loss of binding due to the azide functionality of 3 and 4 abrogating the possibility of two hydrogen bonds to the carbonyl group of Leu231 and Met260 of TGT, previously observed for the terminal methylene amine of preQ1 by x-ray crystallography.

SYNTHESIS OF 7-CYANO-7-DEAZAGUANINE, ONE OF THE NUCLEOSIDE Q (QUEUOSINE) PRECURSORS FOR THE POST-TRANSCRIPTIONAL MODIFICATION OF tRNA

7-Cyano-7-deazaguanine, which is one of the precursors of nucleoside Q (queuosine) biosynthesis, was synthesized from 2-methylthio-6-methoxy-7-methyl-7-diazapurine; methoxymethyl protecting group at 9 position could be removed by transformation to acetoxymethyl group followed by hydrolysis with aq. ammonia.

Creation of an Engineered Amide Synthetase Biocatalyst by the Rational Separation of a Two-Step Nitrile Synthetase

The synthesis of amides through acid and amine coupling is one of the most commonly used reactions in medicinal chemistry, yet still requires atom-inefficient coupling reagents. There is a current demand to develop greener, biocatalytic approaches to amide bond formation. The nitrile synthetase (NS) enzymes are a small family of ATP-dependent enzymes which catalyse the transformation of a carboxylic acid into the corresponding nitrile via an amide intermediate. The Bacillus subtilis QueC (BsQueC) is an NS involved in the synthesis of 7-cyano-7-deazaguanine (CDG) natural products. Through sequence homology and structural analysis of BsQueC we identified three highly conserved residues, which could potentially play important roles in NS substrate binding and catalysis. Rational engineering led to the creation of a NS K163A/R204A biocatalyst that converts the CDG acid into the primary amide, but does not proceed to the nitrile. This study suggests that NSs could be further developed for coupling agent-free, amide-forming biocatalysts.

Design and Synthesis of Pyrrolo[2,3-d]pyrimidine-Derived Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Checkpoint Kinase 1 (CHK1)-Derived Crystallographic Surrogate

Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson’s disease treatment. Fragment hit-derived pyrrolo[2,3-d]pyrimidines underwent optimization using X-ray structures of LRRK2 kinase domain surrogates, based on checkpoint kinase 1 (CHK1) and a CHK1 10-point mutant. (2R)-2-Methylpyrrolidin-1-yl derivative 18 (LRRK2 G2019S cKi0.7 nM, LE 0.66) was identified, with increased potency consistent with an X-ray structure of 18 /CHK1 10-pt. mutant showing the 2-methyl substituent proximal to Ala147 (Ala2016 in LRRK2). Further structure-guided elaboration of 18 gave the 2-[(1,3-dimethyl-1H-pyrazol-4-yl)amino] derivative 32 . Optimization of 32 afforded diastereomeric oxolan-3-yl derivatives 44 and 45 , which demonstrated a favorablein vitroPK profile, although they displayed species disconnects in thein vivoPK profile, and a propensity for P-gp- and/or BCRP-mediated efflux in a mouse model. Compounds 44 and 45 demonstrated high potency and exquisite selectivity for LRRK2 and utility as chemical probes for the study of LRRK2 inhibition.

Synthesis and Anti-HIV Activity of Guanine Modified Fluorinated Acyclic Nucleoside Phosphonate Derivatives

The preparation of an unprecedented series of nucleobase modified 3-fluoro-2-(phosphonomethoxy)propyl (FPMP) acyclic nucleosides in both their (R) and (S) enantiomerically pure forms is described. The synthesis focuses on a Mitsunobu alkylation reaction t

A practical synthesis of archaeosine and its base

A practical synthetic route to 7-formamidino-7-deazaguanosine (archaeosine), a hypermodified nucleoside observed in archaeal tRNA, has been developed, which involves the addition of hydroxylamine to the cyano group of 7-cyano-7-deazaguanosine (preQ0

Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers

IKKβ plays a central role in the canonical NF-kB pathway, which has been extensively characterized. The role of IKKα in the noncanonical NF-kB pathway, and indeed in the canonical pathway as a complex with IKKβ, is less well understood. One major reason for this is the absence of chemical tools designed as selective inhibitors for IKKα over IKKβ. Herein, we report for the first time a series of novel, potent, and selective inhibitors of IKKα. We demonstrate effective target engagement and selectivity with IKKα in U2OS cells through inhibition of IKKα-driven p100 phosphorylation in the noncanonical NF-kB pathway without affecting IKKβ-dependent IKappa-Bα loss in the canonical pathway. These compounds represent the first chemical tools that can be used to further characterize the role of IKKα in cellular signaling, to dissect this from IKKβ and to validate it in its own right as a target in inflammatory diseases.

TREATMENTS FOR AUTOIMMUNE DISEASE

The invention relates to a novel approach to the treatment of autoimmune diseases, particularly multiple sclerosis.In a further embodiment of the invention there is provided a molecule capable of acting as substrate for the queuine-insertase enzyme comple

SUBSTITUTED PYRIMIDINE DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE DISEASES

The present invention describes compounds of formula (I) (I) Wherein: R1 is selected from H and CH3 R2 is selected from H, C4H9 alkyl, C6H13 alkyl and C3H6-