944401-63-2

Upstream product

• 5734-64-5 2-amino-4-chloro-6-methoxypyrimidine 
• 155-90-8 4-methoxypyrimidin-2-amine 
• 36082-45-8 5-bromo-4-methoxypyrimidine-2-ylamine 
• 73183-34-3 bis(pinacol)diborane 

Downstream Products

• 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 
• 1448866-90-7 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 
• 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 
• 1448866-74-7 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 
• 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 
• 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 
• 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 

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.

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.

SUBSTITUTED PURINONE COMPOUNDS

The invention relates to compounds of formula (I): (I) as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of MDM2 and/or MDM4, and combinations comprising such compounds.

IMIDAZOPYRROLIDINONE COMPOUNDS

The invention relates to compounds of formula (I): (I) as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of MDM2 and/or MDM4, and combinations comprising such compounds.

PYRROLOPYRROLIDINONE COMPOUNDS

The invention relates to compounds of formula (I): as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of MDM2 and/or MDM4, and combinations comprising such compounds.

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.