1065075-68-4

Upstream product

• 74840-34-9 4-chloro-2-(methylsulfanyl)pyrimidine-5-carboxylic acid 
• 1003-03-8 Cyclopentamine 
• 5909-24-0 4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester 
• 211245-62-4 4-cyclopentylamino-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester 

Downstream Products

• 571188-82-4 tert?butyl 4?(6?((6?bromo?8?cyclopentyl?5?methyl?7?oxo?7,8?dihydropyrido[2,3?d]pyrimidin?2?yl)amino)pyridin?3?yl)piperazine?1?carboxylate 
• 571189-10-1 4-{6-[8-cyclopentyl-6-(1-ethoxyvinyl)-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino]pyridin-3-yl}piperazine-1-carboxylic acid tert-butyl ester 
• 571190-30-2 PD 0332991 
• 362656-31-3 1-(4-cyclopentylamino-2-methylsulfanylpyrimidin-5-yl)ethanol 
• 211245-64-6 4-cyclopentylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde 
• 362656-11-9 1-(4-cyclopentylamino-2-methylsulfanylpyrimidin-5-yl)ethanone 
• 362656-23-3 8?cyclopentyl?5?methyl?2?(methylthio)pyrido[2,3?d]pyrimidin?7(8H)?one 
• 571188-81-3 6?bromo?8?cyclopentyl?5?methyl?2?(methylsulfinyl)pyrido[2,3?d]pyrimidin?7(8H)?one 
• 1421367-66-9 4-(cyclopentylamino)-2-((2,5-dichlorobenzyl)amino)-N-(3-(2-oxopyrrolidin-1-yl)propyl)pyrimidine-5-carboxamide 
• 1421367-56-7 2-(benzylamino)-4-(cyclopentylamino)-N-(3-(2-oxopyrrolidin-1-yl)propyl)pyrimidine-5-carboxamide 
• 1421367-63-6 2-((2-chlorobenzyl)amino)-4-(cyclopentylamino)-N-(3-(2-oxopyrrolidin-1-yl)propyl)pyrimidine-5-carboxamide 
• 362656-25-5 6-bromo-8-cyclopentyl-5-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one 

Relevant academic research and scientific papers

HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS

Heterocyclic compounds as CDK4 or CDK6 or other CDK inhibitors are provided. The compounds may find use as therapeutic agents for the treatment of diseases and may find particular use in oncology.

Generating Selective Leads for Mer Kinase Inhibitors-Example of a Comprehensive Lead-Generation Strategy

Mer is a member of the TAM (Tyro3, Axl, Mer) kinase family that has been associated with cancer progression, metastasis, and drug resistance. Their essential function in immune homeostasis has prompted an interest in their role as modulators of antitumor immune response in the tumor microenvironment. Here we illustrate the outcomes of an extensive lead-generation campaign for identification of Mer inhibitors, focusing on the results from concurrent, orthogonal high-throughput screening approaches. Data mining, HT (high-throughput), and DECL (DNA-encoded chemical library) screens offered means to evaluate large numbers of compounds. We discuss campaign strategy and screening outcomes, and exemplify series resulting from prioritization of hits that were identified. Concurrent execution of HT and DECL screening successfully yielded a large number of potent, selective, and novel starting points, covering a range of selectivity profiles across the TAM family members and modes of kinase binding, and offered excellent start points for lead development.

4-substituted pyrido [2, 3-d] pyrimidine-7-ketone compound as well as preparation method and application thereof

The invention discloses 4-substituted pyrido [2, 3-d] pyrimidine-7-ketone compounds with different general formula structures and pharmaceutically acceptable salts, solvates, polymorphic substances, tautomers, metabolites or prodrugs of the 4-substituted pyrido [2, 3-d] pyrimidine-7-ketone compounds. The invention also discloses an effect of the compound as an NEDD8 activating enzyme inhibitor and an application of the compound in preparation of drugs for treating diseases related to NEDD8 activating enzyme abnormality. Pharmacological results show that the compound has good NEDD8 inhibitory activity, tumor cell proliferation resistance and tumor cell apoptosis promotion effects.

Design and Development of a Chemical Probe for Pseudokinase Ca2+/calmodulin-Dependent Ser/Thr Kinase

CASK (Ca2+/calmodulin-dependent Ser/Thr kinase) is a member of the MAGUK (membrane-associated guanylate kinase) family that functions as neurexin kinases with roles implicated in neuronal synapses and trafficking. The lack of a canonical DFG motif, which

Structure optimization of positive allosteric modulators of GABAB receptors led to the unexpected discovery of antagonists/potential negative allosteric modulators

Positive allosteric modulators (PAMs) of GABAB receptor represent an interesting alternative to receptor agonists such as baclofen, as they act on the receptor in a more physiological way and thus are devoid of the side effects typically exerted by the agonists. Based on our interest in the identification of new GABAB receptor PAMs, we followed a merging approach to design new chemotypes starting from selected active compounds, such as GS39783, rac-BHFF, and BHF177, and we ended up with the synthesis of four different classes of compounds. The new compounds were tested alone or in the presence of 10 μM GABA using [35S]GTPγS binding assay to assess their functionality at the receptor. Unexpectedly, a number of them significantly inhibited GABA-stimulated GTPγS binding thus revealing a functional switch with respect to the prototype molecules. Further studies on selected compounds will clarify if they act as negative modulators of the receptor or, instead, as antagonists at the orthosteric binding site.

Protection of renal tissues from ischemia through inhibition of the proliferative kinases CDK4 and CDK6

The presently disclosed subject matter relates to methods and compositions for protecting cells and or tissues from damage due to ischemia. In particular, the presently disclosed subject matter relates to the protective action of cyclin dependent kinase 4/6 (CDK4/6) inhibitors administered to subjects that have been exposed to, or that are at risk of, ischemia.

Preparation method for 1-(4-cyclopentylamine-2-methylmercapto-pyrimidine-5-)ethyl ketone

The invention discloses a preparation method for 1-(4-cyclopentylamine-2-methylmercapto-pyrimidine-5-)ethyl ketone. The method comprises the following steps of: (a) adding 4-cyclopentylamine-2-methylmercapto-pyrimidine-5-ethyl formate disclosed by a formula (1) and alkali into organic solvent to react to obtain 4-cyclopentylamine-2-methylmercapto-pyrimidine-5-methanoic acid disclosed in a formula (2); (b) carrying out condensation reaction on the 4-cyclopentylamine-2-methylmercapto-pyrimidine-5-methanoic acid disclosed in the formula (2) and N,O-dimethylhydroxylamine hydrochloride disclosed in a formula (3) to obtain a 4-cyclopentylamine-N-methoxyl-N-methyl-2-methylmercapto-pyrimidine-5-formamide disclosed in a formula (4); and (c) enabling the 4-cyclopentylamine-N-methoxyl-N-methyl-2-methylmercapto-pyrimidine-5-formamide disclosed in the formula (4) to react with methyl magnesium bromide to obtain the1-(4-cyclopentylamine-2-methylmercapto-pyrimidine-5-)ethyl ketone disclosed in a formula (5). The preparation method disclosed by the invention has the advantages of being low in cost and convenient and safe in operation and is easy in large-scale industrial production, and column chromatography isolation purification is not required during postprocessing.

Pyrimidinyl pyridone inhibitors of kinases

This application discloses novel pyrimidinyl pyridone derivatives according to formula I, wherein A, R1, R2, R3, and m are defined as described herein, which inhibit JNK. The compounds disclosed herein are useful to modula