36082-45-8

Usage

Uses

Used in Pharmaceutical Industry:
2-Amino-5-bromo-4-methoxypyrimidine is utilized as a key building block for the synthesis of various pharmaceutical compounds. Its unique structure allows for the creation of diverse medicinal agents, contributing to the development of new treatments and therapies.
Used in Drug Discovery and Development:
As an enzyme inhibitor, 2-Amino-5-bromo-4-methoxypyrimidine serves as a valuable tool in drug discovery and development. Its ability to inhibit certain enzymes can lead to the identification of potential therapeutic agents that target specific biological pathways.
Used in Research and Development:
In the realm of research and development, 2-Amino-5-bromo-4-methoxypyrimidine is employed as an intermediate in the synthesis of other organic compounds. Its versatility in chemical reactions makes it an important component in the creation of novel organic molecules for various applications.
Due to its potential biological and medicinal applications, 2-Amino-5-bromo-4-methoxypyrimidine holds a significant position in the field of organic chemistry and pharmaceutical science, playing a crucial role in advancing our understanding of chemical structures and their implications in medicine.

InChI:InChI=1/C5H6BrN3O/c1-10-4-3(6)2-8-5(7)9-4/h2H,1H3,(H2,7,8,9)

Upstream product

• 155-90-8 4-methoxypyrimidin-2-amine 
• 57054-92-9 5-bromo-2-chloro-4-methoxypyrimidine 
• 1044767-99-8 2-amino-5-bromo-4-chloropyrimidine 
• 5734-64-5 2-amino-4-chloro-6-methoxypyrimidine 

Downstream Products

• 860516-05-8 3-nitro-benzenesulfonic acid-(5-bromo-4-methoxy-pyrimidin-2-ylamide) 
• 1448868-20-9 5-[2-(2-amino-4-methoxy-pyrimidin-5-yl)-6-(4-chloro-phenyl)-1-isopropyl-4-oxo-4,6-dihydro-1H-pyrrolo[3,4-d]imidazol-5-yl]-1,3-dimethyl-1H-pyrimidine-2,4-dione 
• 1448867-98-8 2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(5-chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448867-81-9 4-[(S)-2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(3-chloro-2-fluoro-phenyl)-3-isopropyl-6-oxo-3,4,5,6-tetrahydro-pyrrolo[3,4-d]imidazol-4-yl]-benzonitrile 
• 1448867-82-0 4-[(R)-2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(3-chloro-2-fluoro-phenyl)-3-isopropyl-6-oxo-3,4,5,6-tetrahydro-pyrrolo[3,4-d]imidazol-4-yl]-benzonitrile 
• 1448866-94-1 4-[2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(3-chloro-4-fluoro-phenyl)-3-isopropyl-6-oxo-3,4,5,6-tetrahydro-pyrrolo[3,4-d]imidazol-4-yl]-benzonitrile 
• 1448866-90-7 4-[2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(3-chloro-2-fluoro-phenyl)-3-isopropyl-6-oxo-3,4,5,6-tetrahydro-pyrrolo[3,4-d]imidazol-4-yl]-benzonitrile 
• 1448866-85-0 2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1448866-82-7 4-[2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(5-chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3-isopropyl-6-oxo-3,4,5,6-tetrahydro-pyrrolo[3,4-d]imidazol-4-yl]-benzonitrile 
• 1448866-77-0 4-[2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(5-chloro-2-methyl-phenyl)-3-isopropyl-6-oxo-3,4,5,6-tetrahydro-pyrrolo[3,4-d]imidazol-4-yl]-benzonitrile 
• 1448866-74-7 2-(2-amino-4-methoxy-pyrimidin-5-yl)-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one 
• 1310532-18-3 5-(4-tert-butylamino-3-nitrophenyl)-4-methoxypyrimidin-2-ylamine 
• 944401-63-2 4-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-pyrimidin-2-ylamine 
• 155-90-8 4-methoxypyrimidin-2-amine 

Relevant academic research and scientific papers

Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro

Flaviviruses, such as Dengue (DENV) and Zika (ZIKV) viruses, represent a severe health burden. There are currently no FDA-approved treatments, and vaccines against most flaviviruses are still lacking. We have developed several flexible analogues (“fleximers”) of the FDA-approved nucleoside Acyclovir that exhibit activity against various RNA viruses, demonstrating their broad-spectrum potential. The current study reports activity against DENV and Yellow Fever Virus (YFV), particularly for compound 1. Studies to elucidate the mechanism of action suggest the flex-analogue triphosphates, especially 1-TP, inhibit DENV and ZIKV methyltransferases, and a secondary, albeit weak, effect on the DENV RNA-dependent RNA polymerase was observed at high concentrations. The results of these studies are reported herein.

Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies

Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule, (R)-17, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound (R)-17 effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 μM) and displayed low affinity for hERG (IC50 > 40 μM). Moreover, (R)-17 significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound (R)-17 could be a promising drug candidate for the treatment of hematologic malignancies.

2-polysubstituted aromatic ring-pyrimidine derivative and preparation and medical application

The invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative, an optical isomer of the derivative or a medically acceptable salt or solvate of the derivative, and application of the compound, the optical isomer of the derivative or the medically acceptable salt or solvate of the derivative in preparing antineoplastic medicine. According to the 2-polysubstituted aromatic ring-pyrimidine derivative, by adopting N-substituted pyridine-2-minopyrimidine as a lead compound obtained based on virtual screening of a structure, a series of brand new small molecule Chk1 inhibitors are designed and synthesized, and a Chk1 kinase inhibitory activity test of a molecular level is conducted on the compound. Experiments prove that the compound is a Chk1 inhibitor with a strong antitumous effect, Chk1 kinase inhibitory activity and a prospect, and new cancer treating medicine, and can be used for treating solid tumor or leukemia related with human or animal cell proliferation. The 2-polysubstituted aromatic ring-pyrimidine derivative has a structure shown in the general formula I.

2-MORPHOLIN-4,6-DISUBSTITUTED PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF

Disclosed is a 2-morpholin-4,6-disubstituted pyrimidine derivative as shown in formula (I) below, and a pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof, and a pharmaceutical composition thereof and a use thereof, wherein the definition of each group is as shown in the description. The compound has a PI3K kinase inhibition activity, and has a relatively high inhibitive ability and a low cytotoxicity against PIK3CA mutant breast cancer cell strains T47D and MCF-7.

Discovery of a novel series of potent and orally bioavailable phosphoinositide 3-kinase γ inhibitors

The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3Kγ to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies. The in vitro activity of the first HTS hit, designated as the sulfonylpiperazine scaffold, was optimized utilizing structure-based design. However, nonoptimal pharmacokinetic properties precluded this series from further studies. An overlay of the X-ray structures of the sulfonylpiperazine scaffold and the second HTS hit within their complexes with PI3Kγ revealed a high degree of overlap. This feature was utilized to design a series of hybrid analogues including advanced leads such as 31 with desirable potency, selectivity, and oral bioavailability.

Identification of NVP-BKM120 as a potent, selective, orally bioavailable class i PI3 kinase inhibitor for treating cancer

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.

TRIAZINE COMPOUNDS AS KINASE INHIBITORS

The present invention relates to triazine compounds that are useful as kinase inhibitors. More particularly, the present invention relates to morpholino substituted triazines, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with mTOR kinases or PI3 kinases. The compounds are of the formula (I)

PI 3-KINASE INHIBITORS AND METHODS OF THEIR USE

Phosphatidylinositol (PI) 3-kinase inhibitor compounds, their pharmaceutically acceptable salts, and prodrugs thereof; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases, including proliferative diseases, inflammatory and obstructive airways diseases, allergic conditions, auutoimmune and cardiovascular diseases.

PYRIMIDINE DERIVATIVES USED AS PI-3 KINASE INHIBITORS

Phosphatidylinositol (PI) 3-kinase inhibitor compounds (I), their pharmaceutically acceptable salts, and prodrugs thereof ; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases.