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A dual-catalysis approach to the asymmetric steglich rearrangement and catalytic enantioselective addition of O-acylated azlactones to isoquinolines

A dual-catalysis approach, namely the combination of an achiral nucleophilic catalyst and a chiral anion-binding catalyst, was applied to the Steglich rearrangement to provide alpha,alpha-disubstituted amino acid derivatives in a highly enantioselective fashion. Replacement of the nucleophilic co-catalyst for isoquinoline resulted in a divergent reaction pathway and an unprecedented transformation of O-acylated azlactones. This strategy provided highly substituted alpha,beta-diamino acid derivatives with excellent levels of stereocontrol.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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N-heterocyclic carbene catalyzed enantioselective [3 + 2] dearomatizing annulation of saturated carboxylic esters with n-iminoisoquinolinium ylides

The dearomatizing annulation reaction is a significant challenge in organic chemistry. The direct activation of alpha-carbons of simple saturated esters, as nucleophiles, is an important synthesis strategy. In the present study, we disclose [3 + 2] dearomatizing annulation reactions with direct activating alpha-carbons of saturated carboxylic esters and N-iminoisoquinolinium ylides, which possess highly enantioselective characteristics, catalyzed by N-heterocyclic carbenes (NHCs). The protocol achieves isoquinoline dearomatization and the construction of tricyclic chiral products under mild conditions with good yield, substrate tolerance, and diastereoselectivity as well as excellent enantioselectivity.

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Double Hydroboration of Quinolines via Borane Catalysis: Diastereoselective One Pot Synthesis of 3-Hydroxytetrahydroquinolines

Described herein is an organoborane-catalysed consecutive borylative reduction of quinolines and isoquinolines to furnish tetrahydro(iso)quinolines bearing a C(sp3)?B bond beta to the nitrogen atom. The installed C?B bond is oxidatively transformed to the hydroxy group in one pot. The present double hydroboration is proposed to proceed via a stepwise ionic mechanism involving a boronium ion. The stereo-outcome was found to be dependent on the position (C2 vs C4) of the substituents in quinolines. (Figure presented.).

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Isoquinoline – Wikipedia,
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Synthesis and SAR of indazole-pyridine based protein kinase B/Akt inhibitors

A series of heteroaryl-pyridine containing inhibitors of Akt are reported. The synthesis and structure-activity relationships are discussed, leading to the discovery of a indazole-pyridine analogue (Ki = 0.16 nM). These compounds bind in the ATP binding site, are potent, ATP competitive, and reversible inhibitors of Akt activity. No selectivity amongst the Akt isoforms is observed for this analogue, but there is good selectivity against an panel of other kinases. It is least selective for other members of the AGC family of kinases but is nonetheless 40-fold selective for Akt over PKA. The compound shows cellular activity and significantly slows tumor growth in vivo.

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Isoquinoline – Wikipedia,
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SUBSTITUTED ISOQUINOLINE AND ISOQUINOLINONE DERIVATIVES

The invention relates to 6-substituted isoquinoline and isochinolone derivatives of formula (I) useful in the treatment and prevention of diseases associated with Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds

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Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors

Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P? binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.

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Highly Regioselective Carbamoylation of Electron-Deficient Nitrogen Heteroarenes with Hydrazinecarboxamides

The use of hydrazinecarboxamides as a new class of carbamoylating agents has been established through the dehydrazinative Minisci reaction of electron-deficient nitrogen heteroarenes. A wide range of electron-deficient nitrogen heteroarenes, including isoquinoline, quinoline, pyridine, phenanthridine, quinoxaline, and phthalazine, underwent copper/acid-catalyzed oxidative carbamoylation with hydrazinecarboxamide hydrochlorides to afford structurally diverse nitrogen-heteroaryl carboxamides as single regioisomers in moderate to excellent yields. The functional group tolerance was substantially demonstrated in the direct carbamoylation of quinine obviating multistep sequences involving protecting groups and prefunctionalization of the heterocycle.

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A general Suzuki cross-coupling reaction of heteroaromatics catalyzed by nanopalladium on amino-functionalized siliceous mesocellular foam

Suzuki-Miyaura cross-coupling reactions of heteroaromatics catalyzed by palladium supported in the cavities of amino-functionalized siliceous mesocellular foam are presented. The nanopalladium catalyst effectively couples not only heteroaryl halides with boronic acids but also heteroaryl halides with boronate esters, potassium trifluoroborates, MIDA boronates, and triolborates, producing a wide range of heterobiaryls in good to excellent yields. Furthermore, the heterogeneous palladium nanocatalyst can easily be removed from the reaction mixture by filtration and recycled several times with minimal loss in activity. This catalyst provides an alternative, environmentally friendly, low-leaching process for the preparation of heterobiaryls.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Dehydrogenation of Nitrogen Heterocycles Using Graphene Oxide as a Versatile Metal-Free Catalyst under Air

Graphene oxide (GO) has been developed as an inexpensive, environmental friendly, metal-free carbocatalyst for the dehydrogenation of nitrogen heterocycles. Valuable compounds, such as quinoline, 3,4-dihydroisoquinoline, quinazoline, and indole derivatives, have been successfully used as substrates. The investigation of various oxygen-containing molecules with different conjugated systems indicated that both the oxygen-containing groups and large pi-conjugated system in GO sheets are essential for this reaction. (Figure presented.).

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Discovery of N-(Pyridin-4-yl)-1,5-naphthyridin-2-amines as Potential Tau Pathology PET Tracers for Alzheimer?s Disease

A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified N-(6-methylpyridin-2-yl)quinolin-2-amine 10 as a novel potent binder to human AD aggregated tau with modest selectivity versus aggregated beta-amyloid (Abeta). Initial medicinal chemistry efforts identified key elements for potency and selectivity, as well as suitable positions for radiofluorination, leading to a first generation of fluoroalkyl-substituted quinoline tau binding ligands with suboptimal physicochemical properties. Further optimization toward a more optimal pharmacokinetic profile led to the discovery of 1,5-naphthyridine 75, a potent and selective tau aggregate binder with potential as a tau PET tracer.

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Reference£º
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem