866620-36-2

Upstream product

• 52092-47-4 5-chloro-2-nitropyridine 
• 943758-04-1 1-isopropyl-4-(6-nitropyridin-3-yl)piperazine 
• 4318-42-7 1-(1-methylethyl)piperazine 
• 39856-50-3 5-bromo2-nitropyridine 

Downstream Products

• 1426259-92-8 N-(5-(4-isopropylpiperazin-1-yl)pyridin-2-yl)-4-(pyridin-2-yl)benzamide 
• 1360056-56-9 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate 
• 1360055-91-9 6-tert-Butyl-8-fluoro-2-(2-hydroxymethyl-3-{5-[5-(4-isopropyl-piperazin-1-yl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-one 

Relevant academic research and scientific papers

CDK INHIBITORS

Provided is a compound represented by structural formula (I), or a pharmaceutically acceptable salt, or a stereoisomer thereof useful for treating cancer.

ANTIPROLIFERATIVE PYRIMIDINE-BASED COMPOUNDS

This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.

PYRIMIDINE-BASED ANTIPROLIFERATIVE AGENTS

This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.

PYRIMIDINE-BASED COMPOUNDS FOR THE TREATMENT OF CANCER

This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.

COMBINATIONS AND DOSING REGIMES TO TREAT RB-POSITIVE TUMORS

This invention directed to methods for treating select RB-positive cancers and other Rb- positive abnormal cellular proliferative disorders using CDK4/6 inhibitors in specific dosing and combination or alternation regimes. In one aspect, treatments of select RB-positive cancers are disclosed using specific CDK4/6 inhibitors in combination or alternation with another chemotherapeutic, for example, an additional kinase inhibitor, PD-1 inhibitor, or BCL-2 inhibitor, or combination thereof.

TYK2 INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.

IMIDAZOPYRIDINES SYK INHIBITORS

Certain imidazopyridines (I) and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

TRANSIENT PROTECTION OF NORMAL CELLS DURING CHEMOTHERAPY

This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

Towards optimization of arylamides as novel, potent, and brain-penetrant antiprion lead compounds

The prion diseases caused by PrPSc, an alternatively folded form of the cellular prion protein (PrPC), are rapidly progressive, fatal, and untreatable neurodegenerative disorders. We employed HTS ELISA assays to identify compounds that lower the level of PrPSc in prion-infected mouse neuroblastoma (ScN2a-cl3) cells and identified a series of arylamides. Structure-activity relationship (SAR) studies indicated that small amides with one aromatic or heteroaromatic ring on each side of the amide bond are of modest potency. Of note, benzamide (7), with an EC50 of 2200 nM, was one of only a few arylamide hits with a piperazine group on its aniline moiety. The basic piperazine nitrogen can be protonated at physiologic pH, improving solubility, and therefore, we wanted to exploit this feature in our search for a drug candidate. An SAR campaign resulted in several key analogues, including a set with biaryl groups introduced on the carbonyl side for improved potency. Several of these biaryl analogues have submicromolar potency, with the most potent analogue 17 having an EC50 = 22 nM. More importantly, 17 and several biarylamides (20, 24, 26, and 27) were able to traverse the blood-brain barrier (BBB) and displayed excellent drug levels in the brains of mice following oral dosing. These biarylamides may represent good starting points for further lead optimization for the identification of potential drug candidates for the treatment of prion diseases.

CDK INHIBITORS

Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors.