1604677-77-1

Basic information

• Product Name: 4-chloro-6-(2,3-dichlorophenyl)pyrimidin-2-amine
• Synonyms: 4-chloro-6-(2,3-dichlorophenyl)pyrimidin-2-amine
• CAS NO: 1604677-77-1
• Molecular Weight: 274.537
• Mol File: 1604677-77-1.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: 4-chloro-6-(2,3-dichlorophenyl)pyrimidin-2-amine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-chloro-6-(2,3-dichlorophenyl)pyrimidin-2-amine(1604677-77-1)
• EPA Substance Registry System: 4-chloro-6-(2,3-dichlorophenyl)pyrimidin-2-amine(1604677-77-1)

Safety Data

• Hazardous Substances Data: 1604677-77-1(Hazardous Substances Data)

Upstream product

• 56-05-3 2-Amino-4,6-dichloropyrimidine 
• 151169-74-3 2,3-dichlorobenzeneboronic acid 

Downstream Products

• 1612183-65-9 4-(2-{[2-amino-6-(2,3-dichlorophenyl)pyrimidin-4-yl]amino}ethyl)-N,N-dimethylbenzene-1-sulfonamide 
• 1612183-63-7 6-(2,3-dichlorophenyl)-4-N-[2-(5-methyl-1H-1,2,4-triazol-3-yl)ethyl]pyrimidine-2,4-diamine 
• 1612183-55-7 6-(2,3-dichlorophenyl)-4-N-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]pyrimidine-2,4-diamine 
• 1612182-58-7 6-(2,3-dichlorophenyl)-4-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)pyrimidine-2,4-diamine 
• 1612182-57-6 4-N-[2-(1-benzylpiperidin-4-yl)ethyl]-6-(2,3-dichlorophenyl)pyrimidine-2,4-diamine 

Relevant articles and documents

Radiolabeled 6-(2, 3-dichlorophenyl)-n4-methylpyrimidine-2, 4-diamine (th287): A potential radiotracer for measuring and imaging mth1

MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [3H]TH287 to MTH1 was evaluated in live glioblastoma cells (U251MG) through saturation and competitive binding assays, together with in vitro enzymatic assays. Furthermore, TH287 was radiolabeled with carbon-11 for in vivo microPET studies. Saturation binding assays show that [3H]TH287 has a dissociation constant (Kd) of 1.97 ± 0.18 nM, Bmax of 2676 ± 122 fmol/mg protein for U251MG cells, and nH of 0.98 ± 0.02. Competitive binding assays show that TH287 (Ki: 3.04 ± 0.14 nM) has a higher affinity for MTH1 in U251MG cells compared to another well studied MTH1 inhibitor: (S)-crizotinib (Ki: 153.90 ± 20.48 nM). In vitro enzymatic assays show that TH287 has an IC50 of 2.2 nM in inhibiting MTH1 hydrolase activity and a Ki of 1.3 nM from kinetics assays, these results are consistent with our radioligand binding assays. Furthermore, MicroPET imaging shows that [11C]TH287 gets into the brain with rapid clearance from the brain, kidney, and heart. The results presented here indicate that radiolabeled TH287 has favorable properties to be a useful tool for measuring MTH1 in vitro and for further evaluation for in vivo PET imaging MTH1 of brain tumors and other central nervous system disorders.

Pyrimidines compound and preparation method and application thereof

The invention discloses a pyrimidines compound. The structure of the pyrimidines compound is shown in a formula (I) as shown in the specification, in the formula, R1 is selected from one of hydrogen, halogen, nitro, cyano, hydroxyl, amino, dimethylamino, Cl-6 alkyl, Cl-6 perfluoroalkyls, C2-6 alkenyls, C2-6 alkynyls, C3-6 cycloalkyl, C3-12 heteroalicyclyl or Cl-6 alkoxy, R2 is selected from one of hydrogen, Cl-6 alkyl, C2-6 alkenyls, C2-6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkyloxy, C3-12 heteroalicyclyl, aryl, substituted aryl or a group P, the group P is as shown in the specification, R3 is selected from hydrogen or a group Q, the group Q is as shown in the specification, X is selected from one of Q, S, N or -NHCO-, at least one of the group P and the group Q appears, m is 1-7, and n is 1-7. The pyrimidines compound is 8-hydroxyguanine nucleotidase inhibitor, and can be used for treating diseases caused by abnormity of activity of 8-hydroxyguanine nucleotidase, such as tumors.

MTH1 INHIBITORS FOR TREATMENT OF INFLAMMATORY AND AUTOIMMUNE CONDITIONS

A compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of autoimmune diseases and inflammatory conditions.