90993-29-6

Usage

Uses

Used in Pharmaceutical Industry:
2-Chloro-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one is utilized as a building block in the synthesis of various pharmaceutical drugs. Its distinctive structure and properties contribute to the development of new therapeutic agents, particularly in medicinal and chemical research.
Used in Medicinal Research:
In the field of medicinal research, 2-Chloro-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one serves as a valuable molecule for exploring its potential therapeutic applications. Its unique chemical composition may lead to the discovery of new treatments and advancements in medicine.

Upstream product

• 63200-54-4 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine 
• 116705-41-0 5-Nitro-2,4-dioxo-6-(β-dimethylaminovinyl)-1,2,3,4-tetrahydropyrimidine 
• 65996-50-1 2,4-Dioxo-1,2,3,4-tetrahydropyrrolo<3,2-d>pyrimidine 
• 16632-21-6 5-nitro-6-methyluracil 
• 626-48-2 6-Methyluracil 

Downstream Products

• 1377432-81-9 2-((2-chloro-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-3-yl)methyl)benzonitrile 
• 1377432-69-3 2-((2-((R)-3-aminopiperidin-1-yl)-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-3-yl)methyl)benzonitrile 
• 1377432-84-2 tert-butyl ((3R)-1-(3-(2-cyanobenzyl)-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)piperidin-3-yl)carbamate 
• 1377432-90-0 tert-butyl ((3R)-1-(7-bromo-3-(2-cyanobenzyl)-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)piperidin-3-yl)carbamate 
• 2351929-82-1 2-chloro-3-methyl-3,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one 

Relevant academic research and scientific papers

Rapid generation of a novel DPP-4 inhibitor with long-acting properties: SAR study and PK/PD evaluation

Drug compliance is critical for patients with chronic diseases such as diabetes. In our continuous effort to find better glucose-lowering agents, an exploration for long-acting DPP-4 inhibitors had been launched. Based on our previously reported compounds bearing a pyrrolopyrimidine scaffold, the lead compound 4a (IC50 = 2.3 nM, t1/2(rat) = 5.46 h) with pharmacokinetic superiority was rapidly determined. Further SAR study indicated that the pyrrole ring was generally tolerable for variation, in which a β-substitution gave a better DPP-4 affinity. In depth evaluation of the pyrrole ring β position identified a highly potent compound 12a (IC50 = 0.76 nM, t1/2(rat) = 7.89 h). In vivo pharmacodynamics tests demonstrated similar or even slightly better sustained DPP-4 inhibition for compounds 4a and 12a compared with the first marketed once-weekly drug trelagliptin in this category, indicating that improvements to DPP-4 inhibitory activity or pharmacokinetic profile might be feasible ways to rapidly generate long-acting DPP-4 inhibitors.

Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain

SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumour suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1), we discovered the first potent and selective small molecule SETDB1-TTD inhibitor (R,R)-59 through stepwise structure-guided optimization. (R,R)-59 showed a KD value of 0.088±0.045 μM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biological functions of SETDB1-TTD.

Pyrimidinone derivative and application thereof in pharmacy

The invention discloses a pyrimidinone derivative and application thereof in pharmacy, and particularly relates to a compound shown as a formula (A) or a pharmaceutically acceptable salt, crystal formand solvate thereof. In the formula (A), W, Y, R1, R2, R3 and R4 are as defined in claim 1 of the specification. The affinity between the compound and a PCAF bromine structural domain is relatively high; the compound can strongly bind to the PCAF bromine structural domain, can be used as a PCAF bromine structural domain inhibitor to inhibit interaction between the PCAF bromine structural domain and acetylated lysine, and can be further used as a potential medicine for treating PCAF related diseases or symptoms, such as cancer, HIV infection and neuroinflammation.

Discovery of Pyrrolo[3,2- d]pyrimidin-4-one Derivatives as a New Class of Potent and Cell-Active Inhibitors of P300/CBP-Associated Factor Bromodomain

Herein, we report the discovery of a series of new P300/CBP-associated factor (PCAF) bromodomain (BRD) inhibitors, which were obtained through a hit discovery process and subsequent structure-based optimization and structure-activity relationship analyses toward a retrieved hit compound (12). Among these inhibitors, (R,R)-36n is the most potent one with an IC50 of 7 nM in homogeneous time-resolved fluorescence assay and a KD of 78 nM in isothermal titration calorimetry assay. This compound also exhibited activity against GCN5 and FALZ, but weak or no activity against other 29 BRD proteins and 422 kinases, indicating considerable selectivity. X-ray cocrystal structure analysis revealed the molecular interaction mode and the precise stereochemistry required for bioactivity. Cellular activity, preliminary RNA-seq analysis, and pharmacokinetic properties were also examined for this compound. Collectively, this study provides a versatile tool molecule to explore molecular mechanisms of PCAF BRD regulation and also offers a new lead compound for drug discovery targeting PCAF.

Pyrrolopyrimidine ketone compound and preparation method and application thereof

The invention relates to a pyrrolopyrimidine ketone compound and a preparation method and application thereof, and belongs to the technical field of medicine. The pyrrolopyrimidine ketone compound having a structural feature of formula I, or a pharmaceutically acceptable salt thereof has a very good inhibition effect on DPP-IV, and almost no effect on activity of DPP-VIII and DPP-IX, can effectively control the blood glucose concentration of diabetic rats, and is safe and low in toxicity through the verification of pharmacological and toxicological tests. After being prepared into a medicine, the compound provided by the invention not only has an obvious efficacy but also has very small side effects, thus greatly improving the administration convenience and patient use compliance, therefore, the compound has obvious advantages compared with the same kind of medicine. The formula is shown in the specification.

Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization

A novel dipeptidyl peptidase IV inhibitor hit (5, IC50 = 0.86 μM) was structurally derived from our recently disclosed preclinical candidate 4 by replacing the cyanobenzyl with a butynyl based on pharmacophore hybridization. A hit-to-lead optimization effort was then initiated to improve its potency. Most N-substituted analogs exhibited good in vitro activity, and compound 18o (IC50 = 1.55 nM) was identified to be a potent dipeptidyl peptidase IV inhibitor with a significantly improved pharmacokinetic properties (bioavailablity: 41% vs 82.9%; T1/2: 2 h vs 4.9 h).

Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization

We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.