期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 12, 期 11, 页码 1718-1725出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.1c00344
关键词
Isatin; multicomponent reactions; Ugi reaction; Alzheimer's disease; oxindole-lactam hybrids
资金
- FCT [PD/BD/128490/2017-CATSUS]
- Portuguese Agency for Scientific Research, Fundacao para a Ciencia e a Tecnologia (FCT) [UIDB/00313/2020, UIDP/00313/2020]
- COMPETE2020-UE
- FCT-Foundation for Science and Technology [UIDB/50006/2020]
- Direccion General de Investigacion of Spain [CTQ2016-78703-P]
- Junta de Andalucia [FQM134]
- FEDER [501100008530]
- EU COST Actions [CA15135, CA18133, CA18240]
- FEDER Funds through the Operational Competitiveness Factors Program-COMPETE
The study successfully synthesized oxindole-lactam hybrids using molecular hybridization and multicomponent reactions. The compounds showed potential in inhibiting central nervous system targets, suggesting them as new potential agents for the treatment of Alzheimer's disease.
Molecular hybridization is a valuable approach in drug discovery. Combining it with multicomponent reactions is highly desirable, since structurally diverse libraries can be attained efficiently in an eco-friendly manner. In this work, isatin is used as the key building block for the Ugi 4-center 3-component reaction synthesis of oxindole-lactam hybrids, under catalyst-free conditions. The resulting oxindole-beta-lactam and oxindole-gamma-lactam hybrids were evaluated for their potential to inhibit relevant central nervous system targets, namely cholinesterases and monoamine oxidases. Druglikeness evaluation was also performed, and compounds 4eca and 5dab exhibited great potential as selective butyrylcholinesterase inhibitors, at the low micromolar range, with an interesting predictive pharmacokinetic profile. Our findings herein reported suggest oxindole-lactam hybrids as new potential agents for the treatment of Alzheimer's disease.
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