1670-87-7

Usage

Biological Activity

Selective, orally active, ATP-competitive inhibitor of p38 α MAPK (IC 50 values are 3.2, 122 and > 50000 nM for p38 α , p38 β and p38 γ respectively). Demonstrates no activity against a range of other kinases including ERK2, JNK1 and MAPKAP2. Prevents development of diabetes and alleviates mild and moderate hyperglycaemic states in NOD mice.

references

[1] medicherla s, protter a a, ma j y, et al. preventive and therapeutic potential of p38α-selective mitogen-activated protein kinase inhibitor in nonobese diabetic mice with type 1 diabetes[j]. journal of pharmacology and experimental therapeutics, 2006, 318(1): 99-107.[2] myers r r, sekiguchi y, kikuchi s, et al. inhibition of p38 map kinase activity enhances axonal regeneration[j]. experimental neurology, 2003, 184(2): 606-614.

InChI:InChI=1/C9H8N2O/c10-9(12)7-1-2-8-6(5-7)3-4-11-8/h1-5,11H,(H2,10,12)

Upstream product

• 1011-65-0 5-methoxycarbonylindole 
• 15861-24-2 1H-indole-5-carbonitrile 
• 1670-81-1 1H-Indole-5-carboxylic acid 
• 10075-50-0 5-bromo-1H-indole 
• 15226-74-1 dicobalt octacarbonyl 
• 18169-72-7 trimethylsilyl isocyanide 

Downstream Products

• 1215298-54-6 1-[4-(trifluoromethyl)benzoyl]-1H-indole-5-carboxamide 
• 276863-95-7 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile 
• 143612-79-7 3-(4-chlorobutyl)-5-cyanoindole 
• 81881-74-5 5-aminomethylindole 
• 114948-09-3 5-Thiocarbamoyl-indol 

Relevant academic research and scientific papers

BICYCLIC HETEROARYL DERIVATIVES AS ECTONUCLEOTIDE PYROPHOSPHATASE PHOSPHODIESTERASE 1 INHIBITORS

The present disclosure provides certain bicyclic heteroaryl compounds that inhibit ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzymatic activity and are therefore useful for the treatment of diseases and conditions modulated at least in part by ENPP1. In some embodiments, the bicyclic heteroaryl compounds includes those of Formula (I). Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Bis(allyl)-ruthenium(IV) complexes with phosphinous acid ligands as catalysts for nitrile hydration reactions

Several mononuclear ruthenium(iv) complexes with phosphinous acid ligands [RuCl2(η3:η3-C10H16)(PR2OH)] have been synthesized (78-86% yield) by treatment of the dimeric precursor [{RuCl(μ-Cl)(η3:η3-C10H16)}2] (C10H16 = 2,7-dimethylocta-2,6-diene-1,8-diyl) with 2 equivalents of different aromatic, heteroaromatic and aliphatic secondary phosphine oxides R2P(O)H. The compounds [RuCl2(η3:η3-C10H16)(PR2OH)] could also be prepared, in similar yields, by hydrolysis of the P-Cl bond in the corresponding chlorophosphine-Ru(iv) derivatives [RuCl2(η3:η3-C10H16)(PR2Cl)]. In addition to NMR and IR data, the X-ray crystal structures of representative examples are discussed. Moreover, the catalytic behaviour of complexes [RuCl2(η3:η3-C10H16)(PR2OH)] has been investigated for the selective hydration of organonitriles in water. The best results were achieved with the complex [RuCl2(η3:η3-C10H16)(PMe2OH)], which proved to be active under mild conditions (60 °C), with low metal loadings (1 mol%), and showing good functional group tolerance.

Screening of NOS activity and selectivity of newly synthesized acetamidines using RP-HPLC

Nitric Oxide Synthase (NOS) inhibitors could play a powerful role in inflammatory and neurodegenerative diseases. In this work, novel acetamidine derivatives of NOS were synthesized and the inhibitor activity was evalued. To screen the activity and selectivity, the l-citrulline residue, after the enzymatic NOS assay, was derivatized with o-phthaldialdehyde/N-acetyl cysteine (OPA/NAC) and then evaluated by RP-HPLC method with fluorescence detection.All compounds did not affect the activity of endothelial and neuronal isoforms, while nine of them possessed a percentage of iNOS activity at 10 μM lower than 50%, and were selected for IC50 evaluation. Among them, a compound emerged as a very potent (IC50 of 53 nM) and selective iNOS inhibitor.

Synthesis of primary amides by aminocarbonylation of aryl/hetero halides using non-gaseous NH3 and CO sources

Abstract A practically simple method for the synthesis of primary amides via the palladium-catalysed aminocarbonylation of aromatic halides by using solid sources of gaseous ammonia and carbon monoxide is described. The system tolerated a wide variety of hindered and functionalized aryl/hetero halides and afforded good to excellent yields (69-94%) of the amide. Pharmacologically active Exalamide and Pyrazinecarboxamide were synthesised in high yields to demonstrate the effectiveness of this method.

Design and synthesis of novel 2-(indol-5-yl)thiazole derivatives as xanthine oxidase inhibitors

Xanthine oxidase (XO) inhibitors have been widely used for the treatment of gout. Indole rings are frequently used as active scaffold in designing inhibitors for enzymes. Herein, we describe the structure-activity relationship for novel xanthine oxidase inhibitors based on indole scaffold. A series of novel tri-substituted 2-(indol-5-yl)thiazole derivatives were synthesized, and their in vitro inhibitory activities against xanthine oxidase and in vivo efficacy lowering uric acid level in blood were measured. Among them, 2-(3-cyano-2-isopropylindol-5-yl)-4-methylthiazole-5-carboxylic acid exhibits the most potent XO inhibitory activity (IC50 value: 3.5 nM) and the excellent plasma uric acid lowering activity. Study of structure activity relationship indicated that hydrophobic moiety (e.g., isopropyl) at 1-position and electron withdrawing group (e.g., CN) at 3-position of indole ring and small hydrophobic group (CH3) at 4-position of the thiazole ring enhanced the XO inhibitory activity. Hydrophobic substitution such as isopropyl at 1-position of the indole moiety without any substitution at 2-position has an essential role for enhancing bioavailability and therefore for high in vivo efficacy.

NOVEL COMPOUNDS EFFECTIVE AS XANTHINE OXIDASE INHIBITORS, METHOD FOR PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME

The present invention relates to novel compounds which are effective as an inhibitor for xanthine oxidase, a process for preparing the same, and a pharmaceutical composition comprising a therapeutically effective amount of the same.

COMPOUNDS AND METHODS FOR TREATING PROTEIN FOLDING DISORDERS

The invention is directed to compounds and methods for treating protein folder disorders. In certain embodiments the invention provides compounds and methods for treating neurodegenerative diseases such as Alzheimer's disease, tauopathy, cerebral amyloid angiopathy, Lewy body disease, dementia, Huntington's disease and prion-based spongiform encelopathy. The invention further provides compounds, methods and pharmaceutical compositions for inhibiting tau protein, Aβ protein or α-synuclein protein aggregation.

SYNTHESIS OF SOME 5-SUBSTITUTED INDOLES

A halogen-metal exchange strategy was employed to prepare several 5-substituted indoles from 5-bromoindole.Additional derivatives were elaborated from the formyl, acetyl, thiomethyl, boronic acid and trimethylstannyl analogues thus prepared.