61394-50-1

Usage

Uses

Used in Pharmaceutical Industry:
5-CYANOOXINDOLE is used as a reactant in the preparation of indolinone-based kinase inhibitors for the treatment of various diseases, including cancer and inflammatory disorders. Its incorporation into these inhibitors enhances their potency and selectivity, making them more effective in targeting specific kinases involved in disease progression.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, 5-CYANOOXINDOLE is utilized as a starting material for the synthesis of diverse bioactive compounds with potential therapeutic applications. Its reactivity and functional group compatibility allow for the development of new chemical entities with improved pharmacological properties.
Used in Drug Discovery:
5-CYANOOXINDOLE plays a crucial role in drug discovery efforts, as it can be employed to generate novel lead compounds with potential therapeutic benefits. Its unique structural features enable the design of innovative molecules that can modulate biological targets, offering new avenues for the treatment of various diseases.
Overall, 5-CYANOOXINDOLE is a valuable chemical entity with a wide range of applications in the pharmaceutical and chemical industries, contributing to the advancement of drug development and the discovery of new therapeutic agents.

InChI:InChI=1/C9H6N2O/c10-5-6-1-2-8-7(3-6)4-9(12)11-8/h1-3H,4H2,(H,11,12)

Upstream product

• 15861-24-2 1H-indole-5-carbonitrile 
• 218632-01-0 3-fluoro-4-nitrobenzonitrile 
• 557-21-1 zinc(II) cyanide 
• 20870-78-4 5-bromo-2-indolin-2-one 
• 61394-58-9 3-methylsulfanyl-2-oxo-2,3-dihydro-indole-5-carbonitrile 
• 113423-49-7 3,3-dibromo-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile 

Downstream Products

• 1487412-52-1 chromeno[2,3-b]indole-9-carbonitrile 
• 1487412-47-4 3-[(2-hydroxyphenyl)methylene]-2-oxoindoline-5-carbonitrile 
• 1086280-92-3 C₂HF₃O₂*C₃₂H₂₈N₄O 
• 199328-21-7 5-carbamoyloxindole 
• 220904-92-7 5-Aminomethyl-1,3-dihydro-indol-2-one 
• 1025998-60-0 5-Cyano-1-methyl-2-thioxo-2,3-dihydro-1H-indole-3-carboxylic acid phenylamide 

Relevant academic research and scientific papers

Following Nature’s Footprint: Mimicking the High-Valent Heme-Oxo Mediated Indole Monooxygenation Reaction Landscape of Heme Enzymes

Pathways for direct conversion of indoles to oxindoles have accumulated considerable interest in recent years due to their significance in the clear comprehension of various pathogenic processes in humans and the multipotent therapeutic value of oxindole pharmacophores. Heme enzymes are predominantly responsible for this conversion in biology and are thought to proceed with a compound-I active oxidant. These heme-enzyme-mediated indole monooxygenation pathways are rapidly emerging therapeutic targets; however, a clear mechanistic understanding is still lacking. Additionally, such knowledge holds promise in the rational design of highly specific indole monooxygenation synthetic protocols that are also cost-effective and environmentally benign. We herein report the first examples of synthetic compound-I and activated compound-II species that can effectively monooxygenate a diverse array of indoles with varied electronic and steric properties to exclusively produce the corresponding 2-oxindole products in good to excellent yields. Rigorous kinetic, thermodynamic, and mechanistic interrogations clearly illustrate an initial rate-limiting epoxidation step that takes place between the heme oxidant and indole substrate, and the resulting indole epoxide intermediate undergoes rearrangement driven by a 2,3-hydride shift on indole ring to ultimately produce 2-oxindole. The complete elucidation of the indole monooxygenation mechanism of these synthetic heme models will help reveal crucial insights into analogous biological systems, directly reinforcing drug design attempts targeting those heme enzymes. Moreover, these bioinspired model compounds are promising candidates for the future development of better synthetic protocols for the selective, efficient, and sustainable generation of 2-oxindole motifs, which are already known for a plethora of pharmacological benefits.

CONJUGATES OF AMPK INHIBITORS AND PROTAC DEGRADERS AND RELATED USES

The present disclosure relates to compounds of Formula (I): T-L-D, stereoisomers thereof, prodrugs thereof, and pharmaceutically acceptable salts thereof, wherein T is an AMPK inhibiting moiety; L is a linking moiety; and D is a PROTAC degrading moiety. The present disclosure also relates to uses of the compounds, e.g., to inhibit AMP-Activated protein kinase (AMPK), degrading AMPK protein, and/or treat cancer in a subject.

AMP-ACTIVATED PROTEIN KINASE INHIBITORS AND METHODS OF MAKING AND USING THE SAME

The present disclosure relates to compounds of Formula (I): (I); stereoisomers thereof, prodrugs thereof, and pharmaceutically acceptable salts thereof. The present disclosure also relates to uses of the compounds, e.g., to inhibit AMP-Activated protein kinase (AMPK) and treat cancer in a subject.

SPIROCHROMANE DERIVATIVES

The invention relates to spirochromane derivatives, or pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof, as well as to pharmaceutical compositions containin

SUBSTITUTED (AZA)INDOLE DERIVATIVES

The invention relates to substituted (aza)indole derivatives, or pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof, as well as to pharmaceutical compositions containing them and to their use as modulators of α7 nicotinic acetylcholine receptor activity in a mammalian subject. (I)

Substituted oxindol-3-ylidenes as AMP-activated protein kinase (AMPK) inhibitors

AMP-activated protein kinase (AMPK) is a central metabolic regulator that promotes cancer growth and survival under hypoxia and plays a role in the maintenance of cancer stem cells. A major challenge to interrogating the potential of targeting AMPK in cancer is the lack of potent and selective small molecule inhibitors. Compound C has been widely used as an AMPK inhibitor, but it lacks potency and has a poor selectivity profile. The multi-kinase inhibitor, sunitinib, has demonstrated potent nanomolar inhibition of AMPK activity and has scope for modification. Here, we have designed and synthesized several series of oxindoles to determine the structural requirements for AMPK inhibition and to improve selectivity. We identified two potent, novel oxindole-based AMPK inhibitors that were designed to interact with the DFG motif in the ATP-binding site of AMPK, this key feature evades interaction with the common recptor tyrosine kinase targets of sunitinib. Cellular engagement of AMPK by these oxindoles was confirmed by the inhibition of phosphorylation of acetyl-CoA carboxylase (ACC), a known substrate of AMPK, in myeloid leukemia cells. Interestingly, although AMPK is highly expressed and activated in K562 cells these oxindole-based AMPK inhibitors did not impact cell viability or result in significant cytotoxicity. Our studies serve as a platform for the further development of oxindole-based AMPK inhibitors with therapeutic potential.

Discovery of novel amino-pyrimidine inhibitors of the insulin-like growth factor 1 (IGF1R) and insulin receptor (INSR) kinases; parallel optimization of cell potency and hERG inhibition

The insulin-like growth factor-1 receptor (IGF1R) and closely related insulin receptor (INSR) are receptor tyrosine kinases which have been postulated to play a role in the tumorigenesis of certain cancers. Strategies for inhibiting oncogenic signaling via the IGF1R and INSR include IGF1R antibodies, IGF1/2 antibodies and dual IGF1R/INSR tyrosine kinase inhibitors (TKIs). IGF1R/INSR TKIs linsitinib (OSI-906) and BMS-754807 have progressed to phase II/III clinical studies in cancer patients. We describe here our efforts to develop small molecule dual inhibitors of the IGF1R/INSR receptor kinases based on an amino-pyrimidine structural class. Our main focus was the parallel optimization of cellular potency and off target activity (principally hERG inhibition) through modulation of physicochemical properties and introduction of key structural motifs using a matched molecular pairs approach and hERG homology model.

Dihydroindolone compounds, a process for their preparation and pharmaceutical compositions containing them

Compounds of formula (I): wherein: m and n represent 1 or 2,A represents a pyrrolyl group,X represents a C(O), S(O) or SO2 group,R1 and R2 represent an alkyl group or, together with the nitrogen atom carrying them, form a heterocyclic group,R3 and R4, together with the atoms carrying them, form a heterocyclic group,R5 represents a hydrogen atom or an alkyl group,R6 represents a hydrogen atom or a halogen atom. Medicinal products containing the same which are useful in treating cancer.

Indolinone derivatives and their use in treating disease-states such as cancer

Indolinone derivatives, such as compounds of the formula (I): wherein A, m, n, R1, R2, R3, R5 and R6 are described herein, are disclosed herein as being useful in treating mammal having disease-states alleviated by the inhibition of PDK-1 activity.

Benzylidene-1,3-dihydro-indol-2-one derivatives a receptor tyrosine kinase inhibitors, particularly of Raf kinases

Compounds of general formula (I) wherein: R1is H or optionally joined with R2to form a fused ring selected from the group consisting of five to ten membered aryl, heteroaryl or heterocyclyl rings, R2and R3are in