92952-84-6

Usage

InChI:InChI=1/C5H7ClN2/c6-1-3-8-4-2-7-5-8/h2,4-5H,1,3H2

Upstream product

• 288-32-4 1H-imidazole 
• 107-04-0 1-Bromo-2-chloroethane 
• 1615-14-1 1-(2-Hydroxyethyl)imidazole 
• 5587-42-8 imidazolyl sodium 
• 107-06-2 1,2-dichloro-ethane 

Downstream Products

• 302963-89-9 N-(2-chloro-6-methylphenyl)-2-[[4-[2-(1H-imidazol-1-yl)ethoxy]-3-methoxyphenyl]amino]-5-thiazolecarboxamide 
• 1178894-58-0 3-(1-(2-(1H-imidazol-1-yl)ethyl)-1H-indol-3-yl)-1-phenyl-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione 
• 1178564-42-5 3-(1-(2-(1H-imidazol-1-yl)ethyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(1-methyl-1H-indol-3-yl)-1-phenyl-1H-pyrrole-2,5-dione 
• 1421770-29-7 1-(2-(phenylselanyl)ethyl)-1H-imidazole 
• 62037-81-4 2-(1H-imidazol-1-yl)ethyl methacrylate 
• 1072-63-5 1-vinylimidazole 

Relevant academic research and scientific papers

The first bridged, bifunctional cyclopentadienyl-imidazolylidene ligand and complexes with titanium and zirconium

Starting from imidazole, l-[2-(cyclopenta-2,4-dienyl)ethyl]-3- methylimidazolium iodide (3) was obtained as a mixture of isomers by a simple three-step synthesis. The reaction of 3 with Ti(NEt2)4 or Zr(NEt2)4 by double deprotonation of the imidazolium salt led to the isomerically pure cationic complexes [{η5-C 5H4-(CH2)2-NHC}M(NEt 2)2]+I- (NHC = N-heterocyclic carbene) 4a (M = Ti) and 4b (M = Zr), respectively, in which a cyclopentadienyl and a methylimidazol-2-ylidene unit are linked by an ethylidene-1,2 bridge to form a novel chelating ligand system. In the case of the reaction of 3 with Zr(NEt2)4 the neutral compound [{η5-C 5H4-(CH2)2-NHC}Zr(NEt 2)I2] (5) is formed as an additional product. According to the X-ray structure analyses, the titanium atom of 4a is terracoordinated while no coordinative interaction exists with the iodide anion; on the other hand, in 5 the zirconium centre is pentacoordinated.

Novel RET inhibitors. Pharmaceutical composition and use thereof

The invention belongs to the field of medicines, and relates to a novel RET inhibitor, a pharmaceutical composition and application thereof. , The present invention relates to a compound represented by formula (I), a stereoisomer, a tautomer, an oxynitrid

RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.

Palladium Complexes of Thio/Seleno-Ether Containing N-Heterocyclic Carbenes: Efficient and Reusable Catalyst for Regioselective C-H Bond Arylation

The synthesis of the novel S,CNHC type half-pincer ligand precursors (L1 and L2) is described herein by using the atom economy reactions of 1-(2-(phenylthio)ethyl)-1H-imidazole with benzyl bromide and bromodiphenylmethane, respectively. The analogous reaction of 1-(2-(phenylselanyl)ethyl)-1H-imidazole with 2-bromoethyl phenyl sulfide has also resulted in a imidazolium bromide (L3) which is a precursor of novel S,CNHC,Se type pincer ligand. The route of silver-NHC transmetalation was employed to get the palladium complexes [Pd(L1/L2–HBr)Cl2] (C1 and C2) and [Pd(L3–HBr)Cl]BF4 (C3). The imidazolium bromide (L1–L3) and palladium complexes (C1–C3) were characterized by using multinuclear NMR and HR-MS. The structure and bonding in the complexes C1 and C2 were validated by X-ray crystallography. Thermally robust and moisture/air insensitive palladium complexes C1–C3 have been explored in the catalysis of C–H bond arylation of imidazoles. The protocol operates under mild reaction conditions in air with an excellent regioselective C–H bond arylation at C-5 position in imidazoles. All the complexes were found to be efficient (yield up to 97 % in 12 h) in the catalysis; however, the activating pincer ligand framework containing Pd catalyst C3, was found to be utmost effective among the three catalysts. Only 0.5 mol-% catalyst loading is required to achieve admirable yield of the desired cross-coupled products. A wide range of substrates was examined, and the developed protocol was applicable to all derivatives with high functional group tolerance and greater efficiency. More importantly, the catalyst C3 has also been found recyclable up to five cycles with minor decrease in efficiency which is highly desirable feature for the development of economical and sustainable industrial reaction processes. The PPh3 and Hg poisoning tests have established the complete homogeneous nature of the catalysis.

3,5,7-Substituted Pyrazolo[4,3- d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models

Cyclin-dependent kinases are therapeutic targets frequently deregulated in various cancers. By convenient alkylation of the 5-sulfanyl group, we synthesized 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidines with various substitutions at position 5 with potent antiproliferative activity in non-Hodgkin lymphoma cell lines. The most potent derivative 4.35 also displayed activities across more than 60 cancer cell lines. The kinase profiling confirmed high selectivity of 4.35 toward cyclin-dependent kinases (CDKs) 2, 5, and 9, and the cocrystal with CDK2/cyclin A2 revealed its binding in the active site. Cultured lymphoma cell lines treated with 4.35 showed dephosphorylation of CDK substrates, cleavage of PARP-1, downregulation of XIAP and MCL-1, and activation of caspases, which collectively confirmed ongoing apoptosis. Moreover, 4.35 demonstrated significant activity in various cell line xenograft and patient-derived xenograft mouse models in vivo both as a monotherapy and as a combination therapy with the BCL2-targeting venetoclax. These findings support further studies of combinatorial treatment based on CDK inhibitors.

Controlled introduction of metal cations into polymerizable ionic liquid-polyoxomolybdate hybrid crystals

A polymerizable ionic-liquid cation having methacryl group and imidazolium moieties (denoted as MAImC1) was successfully hybridized with octamolybdate (Mo8O264?, Mo8) to obtain inorganic-organic hybrid crystals containing monovalent metal cations. The hybrid crystals were initially prepared as sodium ion-containing hybrid crystal of MAImC1-Na-Mo8. The sodium cations in MAImC1-Na-Mo8 were exchangeable to other monovalent metal cations such as silver or potassium to form hybrid crystals of MAImC1-Ag-Mo8 or MAImC1-K-Mo8. Their molecular and crystal structures were clearly revealed by single crystal X-ray analyses. The MAImC1-Na-Mo8 hybrid crystal worked as the hybrid monomer, and was found polymerizable by a radical polymerization using AIBN as an initiator to obtain inorganic-organic polymers (P-MAImC1-Na-Mo8). The conductivities of the hybrid monomer and polymer consisting of MAImC1-Na-Mo8 were investigated.

CXCR4 INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

QUINAZOLINE DERIVATIVE

Provided are a quinazoline derivative, a pharmaceutical composition containing the same, a method for preparation of said derivative, and an application of same as an anti-cancer drug.

Synthesis and antiprotozoal activity of novel 2-{[2-(1H-imidazol-1-yl) ethyl]sulfanyl}-1H-benzimidazole derivatives

A series of 19 new 2-{[2-(1H-imidazol-1-yl)ethyl]sulfanyl}-1H-benzimidazole derivatives was synthesized starting from the properly substituted 1,2-phenylendiamine. These compounds have hydrogen or methyl at position 1; while hydrogen, chlorine, ethoxy or methoxycarbonyl group is at position 5 and/or 6. The novel compounds were tested against protozoa Trichomonas vaginalis, Giardia intestinalis and Entamoeba histolytica. Experimental evaluations revealed strong activity for all tested compounds, having IC 50 values in the nanomolar range, which were even better than metronidazole, the drug of choice for these parasites.

PRODRUGS OF FUSED HETEROCYCLIC INHIBITORS OF D-AMINO ACID OXIDASE

The invention relates to prodrugs of fused heterocyclic inhibitors of D-amino oxidase (DAAO) and methods of treating diseases and conditions, wherein modulation of D-amino acid oxidase activity, D-serine levels, D-serine oxidative products and NMDA receptor activity in the nervous system of a mammalian subject is effective.