825619-05-4

Upstream product

• 4659-45-4 2,6-Dichlorobenzoyl chloride 
• 360056-45-7 methyl 4-amino-1H-pyrazole-3-carboxylate 
• 138786-86-4 methyl 4-nitro-1H-pyrazole-3-carboxylate 

Downstream Products

• 825619-04-3 4-(2,6-dichlorobenzamido)-1H-pyrazole-3-carboxylic acid 
• 902156-99-4 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid (1-methanesulphonyl-piperidin-4-yl)-amide 

Relevant academic research and scientific papers

TAIRE FAMILY KINASE INHIBITORS AND USES THEREOF

Provided herein are compounds of Formula (I′) or (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are met

Discovery of novel cyclin-dependent kinase (CDK) and histone deacetylase (HDAC) dual inhibitors with potent in vitro and in vivo anticancer activity

In the current study, we reported a series of novel 1-H-pyrazole-3-carboxamide-based inhibitors targeting histone deacetylase (HDAC) and cyclin-dependent kinase (CDK). The representative compounds N-(4-((2-aminophenyl)carbamoyl)benzyl)-4-(2,6-dichlorobenzamido)-1H-pyrazole-3-carboxamide (7c) and N-(4-(2-((2-aminophenyl)amino)-2-oxoethyl)phenyl)-4-(2,6-dichlorobenzamido)-1H-pyrazole-3-carboxamide (14a) with potent antiproliferative activities towards five solid cancer cell lines, showed excellent inhibitory activities against HDAC2 (IC50 = 0.25 and 0.24 nM respectively) and CDK2 (IC50 = 0.30 and 0.56 nM respectively). In addition, compounds 7c and 14a significantly inhibited the migration of A375 and H460 cells. Further studies revealed that compounds 7c and 14a could arrest cell cycle in G2/M phase and promote apoptosis in A375, HCT116, H460 and Hela cells, which was associated with increasing the intracellular reactive oxygen species (ROS) levels. More importantly, compound 7c possessed favorable pharmacokinetic properties with the intraperitoneal bioavailability of 63.6% in ICR mice, and potent in vivo antitumor efficacy in the HCT116 xenograft model. Our study demonstrated that compound 7c provides a promising strategy for the treatment of malignant tumors.

Discovery of Covalent CDK14 Inhibitors with Pan-TAIRE Family Specificity

Cyclin-dependent kinase 14 (CDK14) and other TAIRE family kinases (CDKs 15–18) are proteins that lack functional annotation but are frequent off-targets of clinical kinase inhibitors. In this study we develop and characterize FMF-04-159-2, a tool compound

Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14

The TAIRE family of kinases are an understudied branch of the CDK kinase family, that have been implicated in a number of cancers. This manuscript describes the design, synthesis and SAR of covalent CDK14 inhibitors, culminating in identification of FMF-0

COMBINATIONS OF PYRAZOLE DERIVATIVES FOR THE INHIBITION OF CDKS AND GSK'S

A combination comprising (a) a compound of formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NR9

PHARMACEUTICAL COMBINATIONS

The invention provides combinations of an ancillary compound of the formula (0): and a compound of the formula (I'): Also provided are crystalline forms of the constituent compounds, methods for making them and their uses in treating cancers.

PHARMACEUTICAL COMBINATIONS

The invention provides a combination comprising an ancillary compound and a compound having the formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R1-A-NR4- or a 5- or 6-membered carbocyclic or h

MEDICAL USE OF CYCLIN DEPENDENT KINASES INHIBITORS

The invention provides the use of a compound for the manufacture of a medicament for the treatment of pain, wherein the compound is a compound of the formula (0) : or a salt or tautomers or N-oxides or solvate thereof; wherein X is a group R1-A

PHARMACEUTICAL COMBINATIONS OF DIAZOLE DERIVATIVES FOR CANCER TREATMENT

The invention provides a combination comprising (or consisting essentially of) an ancillary compound and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein: R1 is 2,6-dichlorophenyl; R2a and R

4- (2,6-DICHLORO-BENZOYLAMINO) -1H-PYRAZOLE-3-CARBOXYLIC ACID (1-METHANESULPHONYL-PIPERIDIN-4-YL) -AMIDE FOR THE TREATMENT OF CANCER

The invention provides the compound of formula (I) 4-(2,6-dichloro-benzoylamino)-1H-pyrazole- 3-carboxylic acid (l-methanesulphonyl-piperidin-4-yl)-amide in a substantially crystalline form, therapeutic uses thereof and pharmaceutical compositions contain