70298-89-4

Usage

Chemical Properties

Light yellow solid

InChI:InChI=1/C10H14N2O/c1-10(2,3)9(13)12-8-4-6-11-7-5-8/h4-7H,1-3H3,(H,11,12,13)

Upstream product

• 504-24-5 4-aminopyridine 
• 3282-30-2 pivaloyl chloride 
• 13534-98-0 3-bromopyridin-4-amine 
• 239137-59-8 3-Bromo-4-(2,2-dimethylpropanoylamino)pyridine 
• 75-98-9 Trimethylacetic acid 

Downstream Products

• 86847-70-3 2,2-Dimethyl-N-<3-(trimethylsilyl)-4-pyridinyl>propanamide 
• 125867-30-3 diphenyl(4-pivaloylamino-3-pyridyl)methanol 
• 121006-60-8 1-(3,4-Dihydro-2H-[1,6]naphthyridin-1-yl)-2,2-dimethyl-propan-1-one 
• 125867-31-4 4-pivaloylaminopyridine-3-carboxylic acid 
• 125867-26-7 N-[3-[hydroxy(phenyl)methyl]pyrydin-4-yl]-2,2-dimethylpropanamide 
• 125867-28-9 (2,4-dichlorophenyl)(4-pivaloylamino-3-pyridyl)methanol 
• 86847-71-4 N-(3-formylpyridin-4-yl)-2,2-dimethylpropanamide 
• 125867-27-8 (2-methoxyphenyl)(4-pivaloylamino-3-pyridyl)methanol 
• 113975-33-0 2,2-dimethyl-N-(3-iodo-4-pyridinyl)propanamide 
• 223742-81-2 N-[3-(4-fluorobenzoyl)-4-pyridinyl]-2,2-dimethylpropanamide 
• 955123-29-2 C₁₀H₁₅N₂BO₃ 
• 52334-53-9 4-amino-3-hydroxy pyridine 
• 169205-98-5 2-Mercaptooxazolo<5,4-c>pyridine 
• 169205-96-3 2-(Methylthio)oxazolo<5,4-c>pyridine 

Relevant academic research and scientific papers

Synthesis and biological assessment of 4,1-benzothiazepines with neuroprotective activity on the Ca2+ overload for the treatment of neurodegenerative diseases and stroke

In excitable cells, mitochondria play a key role in the regulation of the cytosolic Ca2+ levels. A dysregulation of the mitochondrial Ca2+ buffering machinery derives in serious pathologies, where neurodegenerative diseases highlight. Since the mitochondrial Na+/Ca2+ exchanger (NCLX) is the principal efflux pathway of Ca2+ to the cytosol, drugs capable of blocking NCLX have been proposed to act as neuroprotectants in neuronal damage scenarios exacerbated by Ca2+ overload. In our search of optimized NCLX blockers with augmented drug-likeness, we herein describe the synthesis and pharmacological characterization of new benzothiazepines analogues to the first-in-class NCLX blocker CGP37157 and its further derivative ITH12575, synthesized by our research group. As a result, we found two new compounds with an increased neuroprotective activity, neuronal Ca2+ regulatory activity and improved drug-likeness and pharmacokinetic properties, such as clog p or brain permeability, measured by PAMPA experiments.

One-pot homo- and cross-coupling of diazanaphthalenes via C-H substitution: Synthesis of Bis- and Tris-diazanaphthalenes

The transition metal-free coupling reactions of unactivated diazanaphthalenes were studied using only lithium tetramethylpiperidine (LiTMP) reagent. Symmetrical and nonsymmetrical bis-diazanaphthalenes were synthesized in moderate to high yield by homo- and cross-coupling of related monomers. In addition, the single-step synthesis of diquinoxalino [2,3-a: 2', 3'c] phenazine and 2,2': 3', 2″ - terquinoxaline using the appropriate equivalent amount of LiTMP was performed. The products were characterized by means of NMR spectroscopy and HRMS spectrometry.

Design, Synthesis, and Biological Evaluation of 4-Quinoline Carboxylic Acids as Inhibitors of Dihydroorotate Dehydrogenase

We pursued a structure-guided approach toward the development of improved dihydroorotate dehydrogenase (DHODH) inhibitors with the goal of forming new interactions between DHODH and the brequinar class of inhibitors. Two potential residues, T63 and Y356, suitable for novel H-bonding interactions, were identified in the brequinar-binding pocket. Analogues were designed to maintain the essential pharmacophore and form new electrostatic interactions through strategically positioned H-bond accepting groups. This effort led to the discovery of potent quinoline-based analogues 41 (DHODH IC50 = 9.71 ± 1.4 nM) and 43 (DHODH IC50 = 26.2 ± 1.8 nM). A cocrystal structure between 43 and DHODH depicts a novel water mediated H-bond interaction with T63. Additional optimization led to the 1,7-naphthyridine 46 (DHODH IC50 = 28.3 ± 3.3 nM) that forms a novel H-bond with Y356. Importantly, compound 41 possesses significant oral bioavailability (F = 56%) and an elimination t1/2 = 2.78 h (PO dosing). In conclusion, the data supports further preclinical studies of our lead compounds toward selection of a candidate for early-stage clinical development.

Fragment-Based Discovery of Dual JC Virus and BK Virus Helicase Inhibitors

There are currently no treatments for life-threatening infections caused by human polyomaviruses JCV and BKV. We therefore report herein the first crystal structure of the hexameric helicase of JCV large T antigen (apo) and its use to drive the structure-based design of dual JCV and BKV ATP-competitive inhibitors. The crystal structures obtained by soaking our early inhibitors into the JCV helicase allowed us to rapidly improve the biochemical activity of our inhibitors from 18 μM for the early 6-(2-methoxyphenyl)- and the 6-(2-ethoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole hits 1a and 1b to 0.6 μM for triazolopyridine 12i. In addition, we were able to demonstrate measurable antiviral activity in Vero cells for our thiazolopyridine series in the absence of marked cytotoxicity, thus confirming the usefulness of this approach.

Amine Activation: Synthesis of N-(Hetero)arylamides from Isothioureas and Carboxylic Acids

A novel method for N-(hetero)arylamide synthesis based on rarely explored amine activation, rather than classical acid activation, is reported. The activated amines are easily prepared using a three-component reaction with commercial reagents. The new method shows a broad scope including challenging amides not (efficiently) accessible via classical protocols.

METALLOENZYME INHIBITOR COMPOUNDS

The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

PROTEIN KINASE INHIBITORS

The present invention provides a compound incorporating a group of formula (I) wherein: 1 of X, Y and Z is nitrogen and the other 2 are carbon; V is sulpur or carbon; R3 is oxygen or fluorine; R4 is an optionally present C1-3 alkyl group optionally substituted by fluorine; R5 is an optionally present cyclic group with 5-7 heavy atoms in the ring which may be carbocyclic or heterocyclic and aromatic or aliphatic and is optionally substituted, e.g. by a halogen, C1-2 alkyl or fluoroalkyl, OH, OR6, cyano, COOR6, CONHR6, sulfonamide or NHR6, in which R6 is a C1-2 alkyl or fluoroalkyl; at least one of R4 and R5 is present and R4 and R5 may both be present; m and n are each 1 or 2 depending on the identity of V and R3; when n=2 each R3 may be the same or different but are preferably the same, when m=2, each R4 and each R5 may be the same or different but are preferably the same; and W represents hydrogen, carbon, nitrogen, oxygen or sulphur; or incorporating a salt, hydrate or solvate of a group of formula (I); as well as therapeutic uses of these compounds, in particular as inhibitors of protein kinase activity and in the treatment of inflammation, inflammatory conditions and cancer.

Annelated pyridines as highly nucleophilic and Lewis basic catalysts for acylation reactions

New heterocyclic derivatives of 9-azajulolidine have been synthesized and characterized with respect to their nucleophilicity and Lewis basicity. The Lewis basicity of these bases as quantified through their theoretically calculated methyl-cation affinities correlate well with the experimentally measured reaction rates for addition to benzhydryl cations. All newly synthesized pyridines show exceptional catalytic activities in benchmark acylation reactions, which correlate only poorly with Lewis basicity or nucleophilicity parameters. A combination of Lewis basicity with charge and geometric parameters in the framework of a three-component quantitative structure-activity relationship (QSAR) model is, however, highly predictive. Copyright

SUBSTITUTED HETEROCYCLIC AZA DERIVATIVES

The invention relates to heterocyclic aza derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.