Research progress of indole-fused derivatives as allosteric modulators: Opportunities for drug development

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114574 - 114574

Published: March 28, 2023

Allosteric modulation is a direct and effective method for regulating the function of biological macromolecules, which play vital roles in various cellular activities. Unlike orthosteric modulators, allosteric modulators bind to sites distant from protein's orthosteric/active site can have specific effects on or activity without competing with endogenous ligands. Compared traditional offer several advantages, including reduced side effects, greater specificity, lower toxicity, making them promising strategy developing novel drugs. Indole-fused architectures are widely distributed natural products bioactive drug leads, displaying diverse activities that attract interest both chemists biologists discovery. Currently, an increasing number indole-fused compounds exhibited potent modulation. In this review, we provide brief summary examples based complex architecture, highlighting strategies design/discovery structure-activity relationships perspective medicinal chemistry.

Language: Английский

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Fluorinated Protein–Ligand Complexes: A Computational Perspective

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: 128(25), P. 5925 - 5934

Published: June 17, 2024

Fluorine is an element renowned for its unique properties. Its powerful capability to modulate molecular properties makes it attractive substituent protein binding ligands; however, the rational design of fluorination can be challenging with effects on interactions and energies being difficult predict. In this Perspective, we highlight how computational methods help us understand role fluorine in protein–ligand a focus simulation. We underline importance accurate force field, present fluoride channels as showcase biomolecular fluorine, discuss specific like ability form hydrogen bonds aryl groups. put special emphasis disruption water networks entropic effects.

Language: Английский

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Enantioselective Construction of Tetrahydro‐α‐Carbolines via Organocatalytic Friedel‐Crafts alkylation/N‐hemiacetalization of 2‐aminoindoles with Enals

European Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Abstract An efficient organocatalytic asymmetric Friedel‐Crafts alkylation/ N ‐hemiacetalization reaction of 2‐aminoindoles with α,β‐unsaturated aldehydes was developed. By incorporating an amino group at the C2 position indole, nucleophilicity C3 indole and were leveraged to generate enamine‐type ternary synthon. This approach enabled construction a range chiral tetrahydro‐α‐carboline skeletons potential biological activity, delivering moderate excellent yields (46–83 %) achieving outstanding enantioselectivity (up 99 % ee).

Language: Английский

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Highly diastereoselective [3+3] cycloaddition of indolin-3-ones and nitroallylic acetates: Efficient access to polysubstituted dihydropyrano[3,2-b]indoles

Tetrahedron, Journal Year: 2023, Volume and Issue: 133, P. 133275 - 133275

Published: Jan. 20, 2023

Language: Английский

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