345965-99-3

Upstream product

• 21900-45-8 4-bromo-2-methylbenzoyl chloride 
• 765-30-0 Cyclopropylamine 
• 68837-59-2 4-bromo-2-methylbenzoic acid 

Downstream Products

• 345966-00-9 (4-bromo-2-methyl-benzyl)-cyclopropyl-amine 
• 1610680-36-8 N-cyclopropyl-2-methyl-4-(2-(methylsulfonyl)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamide 
• 1610680-23-3 N-cyclopropyl-2-methyl-4-(2-(methylthio)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamide 
• 1610680-22-2 N-cyclopropyl-4-(4-((4-methoxybenzyl)(2-morpholinoethyl)amino)-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazin-8-yl)-2-methylbenzamide 
• 1610679-73-6 N-cyclopropyl-4-(4-((4-methoxybenzyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazin-8-yl)-2-methylbenzamide 
• 1610676-66-8 C₂₈H₂₉F₂N₇O₃*C₂HF₃O₂ 
• 1610676-59-9 N-cyclopropyl-4-(2-(2-fluorophenoxy)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)-2-methylbenzamide 
• 1610676-60-2 N-cyclopropyl-4-(2-(3-fluorophenoxy)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)-2-methylbenzamide 
• 1610676-51-1 N-cyclopropyl-4-(2-(2,3-difluorophenoxy)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)-2-methylbenzamide 
• 1610676-58-8 4-(2-(3-acetamidophenoxy)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)-N-cyclopropyl-2-methylbenzamide 
• 1610676-47-5 N-cyclopropyl-2-methyl-4-(2-(phenylamino)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamide 
• 1610676-27-1 N-cyclopropyl-2-methyl-4-(2-phenoxy-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamide 
• 1610676-50-0 4-(2-(cyclopentyloxy)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)-N-cyclopropyl-2-methylbenzamide 
• 1610676-23-7 4-(2-(cyclopentylamino)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyrazolo[1,5-a][1,3,5]triazin-8-yl)-N-cyclopropyl-2-methylbenzamide 

Relevant academic research and scientific papers

Discovery of Pyrazolo[1,5-a]pyrimidine TTK Inhibitors: CFI-402257 is a Potent, Selective, Bioavailable Anticancer Agent

This work describes a scaffold hopping exercise that begins with known imidazo[1,2-a]pyrazines, briefly explores pyrazolo[1,5-a][1,3,5]triazines, and ultimately yields pyrazolo[1,5-a]pyrimidines as a novel class of potent TTK inhibitors. An X-ray structure of a representative compound is consistent with 11/2 type inhibition and provides structural insight to aid subsequent optimization of in vitro activity and physicochemical and pharmacokinetic properties. Incorporation of polar moieties in the hydrophobic and solvent accessible regions modulates physicochemical properties while maintaining potency. Compounds with enhanced oral exposure were identified for xenograft studies. The work culminates in the identification of a potent (TTK Ki = 0.1 nM), highly selective, orally bioavailable anticancer agent (CFI-402257) for IND enabling studies.

Discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as novel, highly potent and selective, orally bioavailable inhibitors of Tyrosine Threonine Kinase, TTK

TTK/Mps1 is a key kinase controlling progression of cell division via participation in the mitotic spindle assembly checkpoint and is overexpressed in a number of human cancers. Herein we report the discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-y

PYRAZOLOPYRIMIDINE COMPOUNDS

The present teachings provide a compound represented by the following structural formula: (Formula (I)); or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof.

COMBINATIONS FOR THE TREATMENT OF CANCER

The present invention relates to combinations of at least two compounds A and B, compound A being an inhibitor of Mps-1 kinase, and compound B being an inhibitor of an anti-apoptotic protein of the Bcl-2 family. Another aspect of the present invention relates to the use of such combinations as described supra for the preparation of a medicament for the treatment or prophylaxis of a disease, particularly for the treatment of cancer. Another aspect of the present invention relates to the use of an anti- apoptotic protein from the Bcl-2 family as a sensitizer of cells to Mps-1 inhibitors. Another aspect of the present invention relates to the use of the ratio of pro-apoptotic and anti-apoptotic proteins from the Bcl-2 family in a biological sample as a biomarker for a Mps-1 kinase inhibitor treatment.

SUBSTITUTED IMIDAZOPYRIDAZINES

The present invention relates to substituted imidazopyridazine compounds, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

COMBINATION OF A IMIDAZOPYRIDAZINE DERIVATIVE AND A MITOTIC AGENT FOR THE TREATMENT OF CANCER

The present invention relates to a combination comprising an Mps-1 kinase inhibitor and a mitotic inhibitor. The present invention also relates to the use of said combination for the treatment of cancer, in particular of pancreatic cancer, glioblastoma, ovarian cancer, non-small cell lung carcinoma, breast cancer and/or gastric cancer.

PYRAZOLOPYRIMIDINE COMPOUNDS

The present teachings provide a compound represented by structural formula (1-0), or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof.

SUBSTITUTED IMIDAZOPYRIDAZINES

The present invention relates to substituted imidazopyridazine compounds of general formula I in which R3, R5 and A are as defined in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations

6-THIO-SUBSTITUTED IMIDAZOPYRAZINES FOR USE AS MPS-1 AND TKK INHIBITORS IN THE TREATMENT OF HYPERPROLIFERATIVE DISORDERS

The present invention relates to substituted imidazopyrazine compounds of general formula (I): (I) in which R1, R2, R3, R4 and R5 are as defined in the claims, to methods of and intermediates for prep

SUBSTITUTED 6-IMIDAZOPYRAZINES FOR USE AS MPS-1 AND TKK INHIBITORS IN THE TREATMENT OF HYPERPROLIFERATIVE DISORDERS

The present invention relates to substituted imidazopyrazine compounds of general formula (I), in which R1, R2, R3, R4 and R5 are as defined in the claims, to methods of and intermediates for preparin