205672-24-8

Usage

General Description

(5-Bromo-2-chloro-pyrimidin-4-yl)-Methyl-amine is a chemical compound with the molecular formula C5H6BrClN3. It is a derivative of pyrimidine and contains bromine, chloro, and methylamine functional groups. (5-BroMo-2-chloro-pyriMidin-4-yl)-Methyl-aMine has potential applications in the field of medicinal chemistry and pharmaceuticals as a building block or intermediate for the synthesis of various bioactive molecules. The specific properties and uses of (5-Bromo-2-chloro-pyrimidin-4-yl)-Methyl-amine can vary depending on its intended application and the structure of the final product.

Upstream product

• 36082-50-5 2,4-dichloro-5-bromopyrimidine 
• 74-89-5 methylamine 

Downstream Products

• 1374828-69-9 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanenitrile 
• 839708-50-8 2-chloro-4-(methylamino)pyrimidine-5-carbaldehyde 
• 839708-51-9 N-{3-[(2-chloro-4-methylaminopyrimidin-5-ylmethyl)amino]-4-methylphenyl}-3-trifluoromethylbenzamide 
• 839708-52-0 N-(3-(7-chloro-1-methyl-2-oxo-1,4-dihydropyrimido[4,5-d]-pyrimidin-3(2H)-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide 
• 1351759-14-2 (4-(5-bromo-4-(methylamino)pyrimidin-2-ylamino)-3-methoxyphenyl)(morpholino)methanone 

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.

Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies

Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule, (R)-17, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound (R)-17 effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 μM) and displayed low affinity for hERG (IC50 > 40 μM). Moreover, (R)-17 significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound (R)-17 could be a promising drug candidate for the treatment of hematologic malignancies.

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.

Fluorine-18 and carbon-11 labeled radioligands for positron emission tomography (PET) imaging for LRRK2

A method for positron emission tomography (PET) imaging of LRRK2 in tissue of a subject, the method comprising: administering a compound of formula I, formula II or formula III, or a pharmaceutically acceptable salt thereof to the subject, wherein the com

Pyrrolopyrimidine-inhibitors with hydantoin moiety as spacer can explore P4/S4 interaction on plasmin

In the development of plasmin inhibitors, a novel chemotype, pyrrolopyrimidine scaffold possessing two motifs, a hydantoin-containing P4 moiety and a warhead-containing P1 moiety, is uncovered. A unique feature of the new line of the plasmin inhibitors is

2-PHENYLAMINOPYRIMIDINE DERIVATIVES AS KINASE LRRK2 MODULATORS FOR THE TREATMENT OF PARKINSON'S DISEASE

Specific Compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein m, X, R, R2, R3, R, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS

Pyrazole compounds that are modulators of LRRK2, methods of making the compounds, and methods for using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS

Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the com

Discovery of selective LRRK2 inhibitors guided by computational analysis and molecular modeling

Mutations in the genetic sequence of leucine-rich repeat kinase 2 (LRRK2) have been linked to increased LRRK2 activity and risk for the development of Parkinson's disease (PD). Potent and selective small molecules capable of inhibiting the kinase activity of LRRK2 will be important tools for establishing a link between the kinase activity of LRRK2 and PD. In the absence of LRRK2 kinase domain crystal structures, a LRRK2 homology model was developed that provided robust guidance in the hit-to-lead optimization of small molecule LRRK2 inhibitors. Through a combination of molecular modeling, sequence analysis, and matched molecular pair (MMP) activity cliff analysis, a potent and selective lead inhibitor was discovered. The selectivity of this compound could be understood using the LRRK2 homology model, and application of this learning to a series of 2,4-diaminopyrimidine inhibitors in a scaffold hopping exercise led to the identification of highly potent and selective LRRK2 inhibitors that were also brain penetrable.