OPENING NEW CHEMICAL SPACE IN DRUG DISCOVERY
type: CreativeWork
description: Small molecules have always been of interest in chemistry and biology because of their ability to exert powerful effects on the functions of macromolecules comprising living systems. Screening collections or libraries of small molecules is the most common way to identify new chemical modulators of protein function and constitutes one of the bases of medicinal chemistry. While a general consensus has emerged that library size is not decisive, the concept of library diversity, in terms of molecular structure and, more importantly, molecular function, has become crucial, making the efficient creation of functionally diverse small molecule collections a formidable challenge. When a specific biological target is chosen, the compounds considered in the screening process are usually selected or designed on the basis of knowledge of the target structure or mimicking the structure of known natural ligands. Their synthesis can be planned effectively with retrosynthetic analysis (Target-Oriented Synthesis, TOS). However, when the precise nature of the biological target is unknown, the structural features required in potentially interacting small molecules cannot be defined a priori, and a productive approach can be the synthesis and evaluation of molecular libraries that achieve wide coverage of chemical space (Diversity-Oriented Synthesis, DOS). Indeed, the overall aim of DOS is to generate collections of small molecules with a high degree of structural, and thus functional, diversity that interrogates large areas of biologically-intriguing chemical space simultaneously. Within these two general synthetic strategies, the research herein described is focused on the development of new molecular scaffolds, which, in some cases, proved to be promising lead compounds. Within different synthetic approaches, the high potential of the multicomponent reactions with unprecedented components has been exploited and, on the other hand, new protocols have been finely tuned to achieve new t…
abstract: Small molecules have always been of interest in chemistry and biology because of their ability to exert powerful effects on the functions of macromolecules comprising living systems. Screening collections or libraries of small molecules is the most common way to identify new chemical modulators of protein function and constitutes one of the bases of medicinal chemistry. While a general consensus has emerged that library size is not decisive, the concept of library diversity, in terms of molecular structure and, more importantly, molecular function, has become crucial, making the efficient creation of functionally diverse small molecule collections a formidable challenge. When a specific biological target is chosen, the compounds considered in the screening process are usually selected or designed on the basis of knowledge of the target structure or mimicking the structure of known natural ligands. Their synthesis can be planned effectively with retrosynthetic analysis (Target-Oriented Synthesis, TOS). However, when the precise nature of the biological target is unknown, the structural features required in potentially interacting small molecules cannot be defined a priori, and a productive approach can be the synthesis and evaluation of molecular libraries that achieve wide coverage of chemical space (Diversity-Oriented Synthesis, DOS). Indeed, the overall aim of DOS is to generate collections of small molecules with a high degree of structural, and thus functional, diversity that interrogates large areas of biologically-intriguing chemical space simultaneously. Within these two general synthetic strategies, the research herein described is focused on the development of new molecular scaffolds, which, in some cases, proved to be promising lead compounds. Within different synthetic approaches, the high potential of the multicomponent reactions with unprecedented components has been exploited and, on the other hand, new protocols have been finely tuned to achieve new t…
author: MANENTI, MARCO
language: eng
keywords: multicomponent reaction, aminoboronic compound, spirooxindoles, Settore CHIM/06 - Chimica Organica
date published: 2024-01-29
date modified: 2026-07-27T20:19:08Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1024418

PropertyValue
property ID: DOI
value: 10.13130/manenti-marco_phd2024-01-29