69034-08-8

Usage

Synthesis Reference(s)

Tetrahedron Letters, 37, p. 1829, 1996 DOI: 10.1016/0040-4039(96)00129-3

Upstream product

• 50-01-1 guanidine hydrochloride 
• 176214-18-9 N-[3-(dimethylamino)-2-(trifluoromethyl)-2-propenylidene]-N-dimethylammonium chloride 
• 3167-50-8 2-amino-pyrimidine-5-carboxylic acid 
• 109-12-6 2-aminopyrimidine 
• 2314-97-8 iodotrifluoromethane 
• 69034-12-4 2-chloro-5-(trifluoromethyl)pyrimidine 

Downstream Products

• 69034-09-9 2-bromo-5-(trifluoromethyl)pyrimidine 
• 1400997-85-4 (R)-tert-butyl 2-(2-fluoro-4-(5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)morpholine-4-carboxylate 
• 1400997-56-9 (RS)-2-[3-Fluoro-4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester 
• 1400997-18-3 (S)-2-[4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester 
• 1400995-12-1 ((S)-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine 

Relevant academic research and scientific papers

Discovery and Development of a Potent, Selective, and Orally Bioavailable CHK1 Inhibitor Candidate: 5-((4-((3-Amino-3-methylbutyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)picolinonitrile

Checkpoint kinase 1 (CHK1) plays an important role in the DNA damage response pathway, being a potential anti-cancer drug target. In this study, we used a strategy for trifluoromethyl substitution to obtain orally bioavailable CHK1 inhibitors to overcome the limitations of lead compound 1, which can only be administered intravenously. After detailed investigation, we identified compound 6c as an oral CHK1 inhibitor, which demonstrated a considerably higher plasma exposure in mice. Compound 6c also showed good kinase selectivity. Moreover, it exhibited a significant antiproliferative effect in MV-4-11 cells singly and a synergistic effect in combination with gemcitabine in HT-29, A549, and RPMI-8226 cells. Additionally, compound 6c could inhibit tumor growth in the MV-4-11 xenograft mouse model. The combination of 6c and gemcitabine exhibited synergistic effect in the HT-29 xenograft mouse model. Thus, compound 6c was found to be a selective and oral potential anticancer CHK1 inhibitor.

N-polysubstituted pyridine-2-aminopyrimidine derivatives and application thereof

The invention provides N-polysubstituted pyridine-2-aminopyrimidine derivatives and application thereof. The derivatives have a brand-new skeleton, and experimental results show that most of the derivatives have good CHK1 protein inhibition activity and an obvious in-vitro proliferation inhibition effect on hematoma cell strains, and present good tumor cell targeting selectivity in tumor treatmentas a cell cycle checkpoint kinase 1 (CHK1) inhibitor. The synthesis route of the derivatives is reasonable in design; required raw materials are easy to obtain; reaction conditions are mild; the yield of each step is high; operation is easy and convenient; and the method is suitable for industrial production. Therefore, the derivatives provided by the invention can be applied as CHK1 inhibitor totumor treatment. The structure of a general formula I of the derivatives is shown in the specification.

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.

NEMATOCIDAL SULFONAMIDES

Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein Z is O or S; A1, A2, A3 and A4 are independently N or CR1, provided that only one of A1, A2, A3 and A4 is N; and R1, R2, R3 and Q are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling a parasitic nematode comprising contacting the parasitic nematode or its environment with a biologically effective amount of a compound or a composition of the invention.

Trifluoromethylation of various aromatic compounds by CF3I in the presence of Fe(II) compound, H2O2 and dimethylsulfoxide

Trifluoromethylation of aromatic and hetero-aromatic compounds by CF3I in the presence of Fe(II) compound, H2O2 and dimethylsulfoxide was investigated. Various trifluoromethylated benzene derivatives, six-membered nitrogen-containing aromatic compounds and five-membered hetero-aromatic compounds were obtained under mild conditions. General orientation of electrophilic substitution of aromatic compounds was observed similarly as reported in other radical trifluoromethylation previously.

Preparation of novel β-trifluoromethyl vinamidinium salt and its synthetic application to trifluoromethylated heterocycles

β-Trifluoromethylated vinamidinium salt (1) was prepared in high yield by the reaction between 3,3,3-trifluoropropanoic acid and phosphorus oxychloride in N,N,-dimethylformamide at 70°C for 1h. This salt 1 reacted readily with bifunctional nitrogen nucleophiles, such as amidine and hydrazine derivatives, in acetonitrile or dimethyl sulfoxide to furnish the corresponding trifluoromethylated azaheterocycles in good yields.

Derivatives of (pyrimidyloxy)phenoxy-alkanecarboxylic acid and herbicidal compositions thereof

A compound of general formula I: STR1 wherein A, B, D, E, and V are independently chosen from hydrogen, halogen, nitro, cyano, thiocyano, amino, alkyl, alkoxy, alkylthio, alkenyl, cycloalkyl, carbalkoxy, phenyl, phenoxy or phenylthio; R1 and R2 are independently hydrogen, alkyl, alkenyl, alkanoyl, or R1 and R2 together are alkylidene; W is carboxy or a functional derivative thereof or CH2 Z wherein Z is halogen, hydroxy, alkoxy, alkylthio, formyl or amino; and X and Y are oxygen or sulfur.