21901-34-8

Usage

Chemical Properties

Green-yellow solid

InChI:InChI=1/C6H6N2O3/c1-4-2-5(8(10)11)3-7-6(4)9/h2-3H,1H3,(H,7,9)

Upstream product

• 1003-56-1 3-Methyl-1H-pyridin-2-one 
• 1603-40-3 3-methylpyridin-2-ylamine 
• 1003-56-1 3-methylpyridin-2-ol 
• 7697-37-2 nitric acid 
• 5634-52-6 1,1-dimethoxy-propene 
• 14080-32-1 5-nitropyrimidine 
• 22280-56-4 2-chloro-3-methyl-5-nitropyridine 
• 18344-51-9 2-amino-3-methyl-5-nitropyridine 

Downstream Products

• 22280-56-4 2-chloro-3-methyl-5-nitropyridine 
• 868372-07-0 1-(2,4-dimethylbenzyl)-3-methyl-5-nitropyridin-2(1H)-one 

Relevant academic research and scientific papers

RING TRANSFORMATIONS OF 5-NITROPYRIMIDINE VIA INVERSE DIELS-ALDER REACTIONS

5-Nitropyrimidine undergoes inverse Diels-Alder cycloadditions with ketene-N,N-, -O,O- acetals and enamines resulting in pyridine derivatives.The 1H NMR evidence for the 1-N,N-diethylaminopropyne cycloadduct formation is presented.

Reaction of 2-Halo-5-nitropyridines with Hydroxide Ion in Dimethyl Sulfoxide

Addition of aqueous base to sulutions of 2-halo-5-nitropyridines in dimethyl sulfoxide produces a stable substance which forms 2-hydroxy-5-nitropyridine if the molar ratio of hydroxide to pyridine is greater than 2:1.IR and 1H and 13C NMR spectra of the intermediate stable substance indicate that the pyridine ring is cleaved to form this material.An SN(ANRORC) mechanism is proposed for the reaction.

Computer-aided discovery of aminopyridines as novel JAK2 inhibitors

The Janus kinase 2 (JAK2)-mediated signaling pathway plays an important role in controlling cell survival, proliferation, and differentiation. In recent years, genetic, biological, and physiological evidence has established JAK2 inhibitors as effective chemotherapeutic agents for the treatment of many different cancers. For this reason, we sought to identify novel small molecule inhibitors of JAK2. Using Surflex-Dock software, we tested 3010 compounds with known chemical structures in silico for their ability to interact with the JAK2 ATP-binding pocket. We selected the 10 highest-scoring compounds and tested their abilities to inhibit JAK2 activity in vitro. Compound 1a (ethyl 1-(5-((3-methoxyphenyl)carbamoyl)-3-nitropyridin-2-yl)piperidine-4-carboxylate) was identified. Optimization of 1a using docking studies led to the discovery of compounds 1b and 1d, potent JAK2 inhibitors. Furthermore, as V-shaped kinase inhibitors can curve around the protein backbone and access deep into the pocket, we developed a new series of compounds with a non-linear sulfonamide bond. Nine compounds were prepared and evaluated for JAK2 inhibitory effects. Compounds 7e (IC50 = 6.9 μM) and 7h (IC50 = 12.2 μM) showed better JAK2 inhibition, validating our design approach. This study successfully applied virtual screening for hit discovery, and a docking study for hit optimization. In addition, a novel approach to drug discovery, combining structure- and shape-based drug design, facilitated the design of more potent JAK2 inhibitors. The methods provide a guide for future development of inhibitors targeting JAK2 and other kinases.

BICYCLIC HETEROCYCLE DERIVATIVES AS BROMODOMAIN INHIBITORS

The invention relates to novel bicyclic heterocycle derivatives of formula (I) wherein Cy1,Cy2, R1,R2 and L have the meaning given in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula (I) are usefulas bromodomain inhibitors in the treatment or prevention of diseases or disorders where bromodomain inhibition is desired.

IMIDAZOPYRROLIDINONE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE

The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

THE NITROPYRIDINYL ETHYLENEIMINE COMPOUND, THE PHARMACEUTICAL COMPOSITION CONTAINING IT, THE PREPARATION METHOD AND USE THEREOF

The present invention discloses a nitropyridinyl ethyleneimine compound as shown in the formula I and a preparation method of the same, as well as use of the compound in manufacture of a prodrug and in manufacture of a drug for treating a tumor.

Pyrazinone Modulator of Corticotropin-Releasing Factor Receptor Activity

The invention relates to the compound (S)-4-(1-cyclopropyl-2-methoxyethyl)-6-(6-(difluoromethoxy)-2,5-dimethylpyridin-3-ylamino)-5-oxo-4,5-dihydropyrazine-2-carbonitrile, pharmaceutical compositions of the compound, and methods of using the compound for the treatment of psychiatric disorders and neurological diseases including depression, anxiety related disorders, irritable bowel syndrome, addiction and negative aspects of drug and alcohol withdrawal, and other conditions associated with CRF.

A strategy to minimize reactive metabolite formation: Discovery of (S)-4-(1-cyclopropyl-2-methoxyethyl)-6-[6-(difluoromethoxy)-2, 5-dimethylpyridin-3-ylamino]-5-oxo-4,5-dihydropyrazine-2-carbonitrile as a potent, orally bioavailable corticotropin-releasing factor-1 receptor antagonist

Detailed metabolic characterization of 8, an earlier lead pyrazinone-based corticotropin-releasing factor-1 (CRF1) receptor antagonist, revealed that this compound formed significant levels of reactive metabolites, as measured by in vivo and in vitro biotransformation studies. This was of particular concern due to the body of evidence suggesting that reactive metabolites may be involved in idiosyncratic drug reactions. Further optimization of the structure-activity relationships and in vivo properties of pyrazinone-based CRF1 receptor antagonists and studies to assess the formation of reactive metabolites led to the discovery of 19e, a high affinity CRF1 receptor antagonist (IC50= 0.86 nM) wherein GSH adducts were estimated to be only 0.1% of the total amount of drug-related material excreted through bile and urine, indicating low levels of reactive metabolite formation in vivo. Anovel 6-(difluoromethoxy)-2,5-dimethylpyridin-3- amine group in 19e contributed to the potency and improved in vivo properties of this compound and related analogues. 19e had excellent pharmacokinetic properties in rats and dogs and showed efficacy in the defensive withdrawal model of anxiety in rats. The lowest efficacious dose was 1.8 mg/kg. The results of a two-week rat safety study with 19e indicated that this compound was well-tolerated.

CYCLIC COMPOUNDS

There is provided a CRF receptor antagonist comprising a compound of the formula (I): A-W-Ar wherein, A is a group represented by the formula (A1) or (A2) (wherein, ring Aa is a 5-or 6-membered ring which may be further substituted; ring Ab is a 5-or 6-membered ring which may be further substituted; ring Ac is a 5- or 6-membered ring which may be substituted; R1 is optionally substituted alkyl, substituted amino, substituted hydroxy, etc.; X is carbonyl, -O-, -S-, etc.; Y1, Y2 and Q are independently optionally substituted carbon or nitrogen; … is a single or double bond); W is a bond, optionally substituted methylene, optionally substituted imino, -O-, -S-, etc.; Ar is optionally substituted aryl or optionally substituted heteroaryl; or a salt thereof or a prodrug thereof.