22245-95-0

Usage

Uses

Used in Pharmaceutical Applications:
7-CHLORO-3,4-DIHYDRO-2H-ISOQUINOLIN-1-ONE is used as a chemical compound in medicinal chemistry research for the development of new drugs and therapeutic agents. Its unique structural features, such as the isoquinoline ring system and chloro substituent, may contribute to its biological activities, making it a valuable asset in the discovery and design of novel pharmaceuticals.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, 7-CHLORO-3,4-DIHYDRO-2H-ISOQUINOLIN-1-ONE is used as a starting material or intermediate for the synthesis of various drug candidates. Its structural features can be further modified or functionalized to explore its potential as a therapeutic agent, targeting specific biological pathways or receptors.
Used in Drug Discovery:
7-CHLORO-3,4-DIHYDRO-2H-ISOQUINOLIN-1-ONE is employed in drug discovery processes to identify and optimize potential drug candidates. Its unique structural features can be leveraged to design molecules with improved pharmacological properties, such as increased potency, selectivity, and reduced side effects.
Used in Drug Development:
In the drug development phase, 7-CHLORO-3,4-DIHYDRO-2H-ISOQUINOLIN-1-ONE can be used to evaluate the safety, efficacy, and pharmacokinetic properties of newly synthesized drug candidates. Its structural features may provide insights into the optimization of drug candidates, leading to the development of more effective and safer therapeutic agents.
Overall, 7-CHLORO-3,4-DIHYDRO-2H-ISOQUINOLIN-1-ONE is a versatile chemical compound with potential applications in various stages of pharmaceutical research and development, from drug discovery to drug development. Its unique structural features make it a valuable tool for the design and optimization of novel therapeutic agents.

Upstream product

• 55121-08-9 1-chloro-3-(2-isocyanatoethyl)benzene 
• 2492-83-3 2-(4-chlorophenyl)ethanamine hydrochloride 
• 104-88-1 4-chlorobenzaldehyde 
• 156-41-2 4-chlorophenylethylamine 
• 706-07-0 1-chloro-4-(2-nitrovinyl)benzene 
• 328281-40-9 2-4-chlorophenylethylcarbamic acid methyl ester 
• 17608-10-5 2-(4-chlorophenyl)ethyl isothiocyanate 

Downstream Products

• 104576-30-9 1-phenyl-7-chloro-3,4-dihydroisoquinoline 
• 439116-79-7 tert-butyl 2-[4-chloro-2-(hydroxymethyl)phenyl]-ethylcarbamate 
• 1231892-74-2 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-1(2H)-one 
• 439116-80-0 2-(2-(tert-butoxycarbonylamino)ethyl)-5-chlorobenzyl azide 
• 439116-12-8 tert-butyl 2-[2-(aminomethyl)-4-chlorophenyl]ethylcarbamate 
• 82771-60-6 7-chloro-1,2,3,4-tetrahydro-isoquinoline 

Relevant academic research and scientific papers

Intramolecular Reductive Cyclization of o-Nitroarenes via Biradical Recombination

A visible-light-induced/thiourea-mediated intramolecular cyclization of o-nitroarenes under mild conditions is realized for the first time, which provides an efficient and environmentally friendly way to access pharmaceutical relevant quinazolinone derivatives. The reaction can be easily extended to gram level by using a continuous-flow setup with high efficiency. Mechanistic investigation including control experiments, transient fluorescence, UV-vis spectra, and DFT calculations suggests that the formation of active biradical intermediates via intramolecular single electron transfer (SET) is key stage in the catalytic cycle.

Metal-Free Synthesis of Polycyclic Quinazolinones Enabled by a (NH4)2S2O8-Promoted Intramolecular Oxidative Cyclization

An efficient metal-free, (NH4)2S2O8 mediated intramolecular oxidative cyclization for the construction of polycyclic heterocycles was disclosed. A series of polycyclic quinazolinone derivatives with good functional group tolerance were obtained in high yields. The natural products tryptanthrin and rutaecarpine, as well as their derivatives, were easily synthesized by this strategy. A preliminary mechanism study suggested the carbon-centered radical was involved in the catalytic cycle.

Catalyst-free cyclization of anthranils and cyclic amines: One-step synthesis of rutaecarpine

An efficient synthesis of a variety of quinazolinone derivatives via a direct cyclization reaction between commercially available anthranils and cyclic amines is described. The developed transformation proceeds with the merits of high step- and atom-efficiency, a broad substrate scope, and good to excellent yields, without additional catalysts, and offers a practical way for the preparation of rutaecarpine and its derivatives with structural diversity.

TfOH-Promoted Transition-Metal-Free Cascade Trifluoroethylation/Cyclization of Organic Isothiocyanates by Phenyl(2,2,2-trifluoroethyl)iodonium Triflate

An efficient and transition-metal-free method for the synthesis of the structurally diversified trifluoroethylthiol phenanthridines and 3,4-dihydroisoquinolines is described. Various 2-isothiocyanobiaryls and aryl alkyl isothiocyanates reacted with phenyl(2,2,2-trifluoroethyl)iodonium triflate in CH2Cl2 in the presence of trifluoromethanesulfonic acid at 40 °C to form the corresponding trifluoroethylation/cyclization products in good to quantitative yields. This work represents the first construction of trifluoroethylthiol phenanthridine and isoquinoline derivatives from isothiocyanates in the absence of transition-metal catalysts by a one-pot procedure.

Fragment-Based Discovery of a Potent, Orally Bioavailable Inhibitor That Modulates the Phosphorylation and Catalytic Activity of ERK1/2

Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signaling through ERK1/2. Here, we describe the fragment-based generation of ERK1/2 inhibitors that block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK. X-ray crystallographic and biophysical fragment screening followed by structure-guided optimization and growth from the hinge into a pocket proximal to the C-α helix afforded highly potent ERK1/2 inhibitors with excellent kinome selectivity. In BRAF mutant cells, the lead compound suppresses pRSK and pERK levels and inhibits proliferation at low nanomolar concentrations. The lead exhibits tumor regression upon oral dosing in BRAF mutant xenograft models, providing a promising basis for further optimization toward clinical pERK1/2 modulating ERK1/2 inhibitors.

One-Pot N-Deprotection and Catalytic Intramolecular Asymmetric Reductive Amination for the Synthesis of Tetrahydroisoquinolines

A one-pot N-Boc deprotection and catalytic intramolecular reductive amination protocol for the preparation of enantiomerically pure tetrahydroisoquinoline alkaloids is described. The iodine-bridged dimeric iridium complexes displayed superb stereoselectivity to give tetrahydroisoquinolines, including several key pharmaceutical drug intermediates, in excellent yields under mild reaction conditions. Three additives played important roles in this reaction: Titanium(IV) isopropoxide and molecular iodine accelerated the transformation of the intermediate imine to the tetrahydroisoquinoline product; p-toluenesulfonic acid contributed to the stereocontrol.

BENZOLACTAM COMPOUNDS AS PROTEIN KINASE INHIBITORS

The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof. The compounds are inhibitors of ERK 1/2 kinases and will be useful in the treatment of ERKl/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.

Facile synthesis of 5-To 7-membered benzolactam compounds via strongly facilitated electrophilic aromtic substitution reaction

We employed our system to activate aromatic ring-Tethered carbamate compounds with trifluoromethanesulfonic acid to obtain benzolactams with 5-To 7-membered rings, and examined the substrate scope and limitations of this activation method. In 5-membered ring formation, a halogen group on the aromatic ring did not greatly affect the reaction yield, but other electron-donating groups inhibited the cyclization reaction, and various side-reactions occurred. In 7-membered ring formation, eletron-donating groups on aromatic ring promoted the cyclization reaction, but cyclization of electron-deficient aromatic rings did not proceed well. The 6-membered ring formation reaction showed the greatest substrate generality.

17a-HYDROXYLASE/C17,20-LYASE INHIBITORS

The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.

Activation of electrophilicity of stable Y-delocalized carbamate cations in intramolecular aromatic substitution reaction: Evidence for formation of diprotonated carbamates leading to generation of isocyanates

Although cations with three heteroatoms, such as monoprotonated guanidine and urea, are stabilized by Y-shaped conjugation and such Y-conjugated cations are sufficiently basic to be further protonated (or protosolvated) to dications in strongly acid media, only O-monoprotonated species have been detected in the case of carbamates even in magic acid. We found that the trifluoromethanesulfonic acid-catalyzed cyclization of arylethylcarbamates proceeds to afford dihydroisoquinolones in high yield. In strong acids, methyl carbamates are fully O-monoprotonated, and these monocations do not undergo cyclization even under heating. But, as the acidity of the reaction medium is further increased, the cyclization reaction of methyl phenethylcarbamates starts to proceed as a first-order reaction, with a linear relationship between rate and acidity. The sign and magnitude of the entropy of activation ΔS ? were found to be similar to those of other AAc1 reactions. These results strongly support the idea that further protonation of the O-protonated carbamates is involved in the cyclization, but the concentration of the dications is very low and suggests that the rate-determining step is dissociation of methanol from the diprotonated carbamate to generate protonated isocyanate, which reacts with the aromatic ring. Therefore, O-protonated carbamates are weak bases in sharp contrast to other Y-shaped monocations.