5305-59-9

Usage

Chemical Properties

Pale Yellow Solid

InChI:InChI=1/C4H4ClN3/c5-3-1-4(6)8-2-7-3/h1-2H,(H2,6,7,8)

Upstream product

• 1193-22-2 6-Amino-3,4-dihydropyrimidin-4-one 
• 91-66-7 N,N-diethylaniline 
• 1004-40-6 4-aminothiouracil 
• 1193-22-2 6-amino-4-hydroxy-[3,4-d]pyrimidine 
• 1193-21-1 4,6-dichloropyrimidine 
• 71-36-3 butan-1-ol 

Downstream Products

• 96225-80-8 6-(morpholin-4-yl)pyrimidin-4-amine 
• 99180-36-6 N⁴-cyclohexyl-pyrimidine-4,6-diyldiamine 
• 104296-46-0 N⁴-m-tolyl-pyrimidine-4,6-diyldiamine 
• 108484-95-3 N⁴-butyl-pyrimidine-4,6-diyldiamine 
• 98335-15-0 N⁴-allyl-pyrimidine-4,6-diyldiamine 
• 66131-69-9 N⁶-methylpyrimidin-4,6-diamine 
• 109817-01-8 N⁴-methyl-N⁴-phenyl-pyrimidine-4,6-diyldiamine 
• 93276-70-1 2-(2,4-dimethoxyphenyl)-7-chloroimidazo<1,2-c>pyrimidine hydrobromide 
• 105475-42-1 N⁴-(1-phenyl-ethyl)-pyrimidine-4,6-diyldiamine 
• 564483-84-7 6-amino-4(2-diphenylborinic ester) ethylamino pyrimidine 
• 865604-27-9 (7-chloro-imidazo[1,2-c]pyrimidin-2-yl)-carbamic acid ethyl ester 
• 890128-99-1 6-(6-amino-pyrimidin-4-ylethynyl)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide 
• 872510-67-3 N-(4-diethylamino-phenyl)-pyrimidine-4,6-diamine 
• 945978-33-6 (6-chloro-pyrimidin-4-yl)-(3-cyclopentyloxy-4-methoxy-benzyl)-amine 

Relevant academic research and scientific papers

Potent 2-[(pyrimidin-4-yl)amine}-1,3-thiazole-5-carbonitrile-based inhibitors of VEGFR-2 (KDR) kinase

Pyrimidino-thiazolyl carbonitriles were prepared that are potent VEGFR-2 (KDR) kinase inhibitors. The modification of lead structures resulted in 3m which exhibited the best overall profile in KDR inhibitory activity, iv/po pharmacokinetics, and reduced hERG affinity.

Pyrimidine hydrazone derivative and preparation method and application thereof

The invention relates to pyrimidine hydrazone derivatives as shown in a chemical structural formula I or II, pharmaceutically acceptable salts and pharmaceutical compositions thereof, and an application of the pyrimidine hydrazone derivatives and the pharmaceutically acceptable salts and the pharmaceutical compositions in preparation of influenza virus neuraminidase inhibitors, wherein X is selected from: fluorine, chlorine, bromine, hydroxyl, dihydroxy, 2-hydroxy-3-methoxy, 2-hydroxy-4-methoxy, 2-hydroxy-5-C1-C2 alkoxy, 2-hydroxy-6-C1-C2 alkoxy, 3-hydroxy-2-C1-C2 alkoxy, 3-hydroxy-4-C1-C2 alkoxy, 3-hydroxy-5-methyl C1-C2 alkoxy , 3-hydroxy-6-C1-C2 alkoxy, 4-hydroxy-2-C1-C2 alkoxy, 4-hydroxy-3-C1-C2 alkoxy, 4-hydroxy-3, 5-diC1-C2 alkoxy, trihydroxy or 4-hydroxy-3,5-dimethyl; and Y is selected from: fluorine, chlorine, bromine, acetamido, hydroxyl or methoxy.

Discovery of novel dual inhibitors of receptor tyrosine kinases EGFR and PDGFR-β related to anticancer drug resistance

With ongoing resistance problems against the marketed EGFR inhibitors having a quinazoline core scaffold there is a need for the development of novel inhibitors having a modified scaffold and, thus, expected lower EGFR resistance problems. An additional problem concerning EGFR inhibitor resistance is an observed heterodimerization of EGFR with PDGFR-β that neutralises the sole inhibitor activity towards EGFR. We developed novel pyrimido[4,5-b]indoles with varied substitution patterns at the 4-anilino residue to evaluate their EGFR and PDGFR-β inhibiting properties. We identified dual inhibitors of both EGFR and PDGFR-β in the nanomolar range which have been initially screened in cancer cell lines to prove a benefit of both EGFR and PDGFR-β inhibition.

Discovery of wtRET and V804MRET Inhibitors: From Hit to Lead

Oncogenic activation of RET kinase has been found in several neoplastic diseases, like medullary thyroid carcinoma, multiple endocrine neoplasia, papillary thyroid carcinoma, and non-small-cell lung cancer. Currently approved RET inhibitors were not originally designed to be RET inhibitors, and their potency against RET kinase has not been optimized. Hence, novel compounds able to inhibit both wild-type RET (wtRET) and its mutants (e.g., V804MRET) are needed. Herein we present the development and the preliminary evaluation of a new sub-micromolar wtRET/V804MRET inhibitor, N-(2-fluoro-5-trifluoromethylphenyl)-N′-{4′-[(2′′-benzamido)pyridin-4′′-ylamino]phenyl}urea (69), endowed with a 4-anilinopyridine structure, starting from our previously identified 4-anilinopyrimidine hit compound. Profiling against a panel of kinases indicated 69 as a multi cKIT/wtRET/V804MRET inhibitor.

BTK INHIBITOR

Provided are a series of BTK inhibitors, and specifically disclosed are a compound, pharmaceutically acceptable salt thereof, tautomer thereof or prodrug thereof represented by formula (I), (II), (III) or (IV).

Integrating docking scores, interaction profiles and molecular descriptors to improve the accuracy of molecular docking: Toward the discovery of novel Akt1 inhibitors

A set of forty-seven Akt1 inhibitors was used for the development of molecular docking based QSAR model by using nonlinear regression. The integration of docking scores, key interaction profiles and molecular descriptors remarkably improved the accuracy of the QSAR models, providing reasonable statistical parameters (Rtrain2 = 0.948, R test2 = 0.907 and Qcv2 = 0.794). The established MD-SVR model based structural modification of new 4-amino-pyrimidine derivatives was further performed, and six compounds 56a,b and 60a-d with good prediction activities were synthesized and biologically evaluated. All of these compounds exhibited promising Akt1 inhibitory and antiproliferative activities, suggesting the reliability and good application value of the established MD-SVR model in the development of Akt1 inhibitors.

Reaction kinetics in liquid ammonia up to 120°C: Techniques and some solvolysis and substitution reactions

Liquid ammonia is known to be a useful solvent for aromatic nucleophilic substitution reactions of reactive aromatics. Most of the prior work has been carried out at atmospheric pressure and low temperatures. The purpose of this work is to extend the scope of these studies to less reactive haloaromatic substrates that require elevated temperatures to give useful reaction rates. Equipment has been developed to permit the safe study of reactions in liquid ammonia in small (5 mL) stainless steel tube reactors at temperatures up to 120°C (90 bar). Experimental techniques have been developed to permit meaningful sampling of solutions at high temperature and pressure. Sample capture into closed systems, either into a syringe containing quench solution, or directly into an HPLC sample loop, has been used to overcome problems due to flash precipitation and aerosol formation when sampling from high pressure. Activation parameters for the solvolysis of 4-fluoronitrobenzene have been determined over the temperature range 20° - 120°C, and the rates of solvolysis of 2-chloropyrimidine, 4,6-dichloropyrimidine and 2-chloro-5-trifluoromethylpyridine have been determined at appropriate temperatures. 2-Fluoropyridine is inert to solvolysis even at 120°C. Rates of some nucleophilic substitutions with sodium triazolate and sodium phenoxide have been measured. Useful selectivities towards nucleophilic substitution can be obtained for the reactions examined, and further work is planned to examine the wider scope of these reactions. Copyright 2013 John Wiley & Sons, Ltd. Equipment has been developed to permit the safe study of reactions in liquid ammonia in small (5 mL) stainless steel tube reactors at temperatures up to 120°C (90 bar). Activation parameters for the solvolysis of 4-fluoronitrobenzene have been determined over the temperature range 20° - 120°C, and the rates of solvolysis of 2-chloropyrimidine, 4,6-dichloropyrimidine and 2-chloro-5-trifluoromethylpyridine have been determined at appropriate temperatures. Rates of some aromatic nucleophilic substitutions with sodium triazolate and sodium phenoxide have been measured. Copyright

AZABENZOTHIAZOLE COMPOUNDS, COMPOSITIONS AND METHODS OF USE

Provided are compounds of Formula I, stereoisomers, tautomers, solvates, prodrugs and pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R4 and R5 are defined herein, a pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, methods of using the compound or composition in therapy, and methods of 5 manufacturing a compound of Formula I

SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF

This invention provides compounds of formula (I): wherein R1, R1b, R2a, R2b, R2c, and R2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl- piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase

A novel series of N-aryl-N′-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the b