From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold

Angela Rampa; Francesca Mancini; Angela De Simone; Federico Falchi; Federica Belluti; Rita Maria Concetta Di Martino; Silvia Gobbi; Vincenza Andrisano; Andrea Tarozzi; Manuela Bartolini; Andrea Cavalli; Alessandra Bisi

doi:10.1016/j.bmcl.2015.05.002

From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold

Angela Rampa, Francesca Mancini, Angela De Simone, Federico Falchi, Federica Belluti, Rita Maria Concetta Di Martino, Silvia Gobbi, Vincenza Andrisano, Andrea Tarozzi, Manuela Bartolini, Andrea Cavalli, Alessandra Bisi

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer's disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC₅₀ = 2.49 ± 0.08 μM), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series.

Lingua originale	Inglese
pagine (da-a)	2804-2808
Numero di pagine	5
Rivista	Bioorganic and Medicinal Chemistry Letters
Volume	25
Numero di pubblicazione	14
DOI	https://doi.org/10.1016/j.bmcl.2015.05.002
Stato di pubblicazione	Pubblicato - 4 giu 2015
Pubblicato esternamente	Sì

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10.1016/j.bmcl.2015.05.002

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title = "From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold",

abstract = "In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer's disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC50 = 2.49 ± 0.08 μM), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series.",

keywords = "AChE, Alzheimer's disease, BACE1, Drug discovery, Indanone",

author = "Angela Rampa and Francesca Mancini and {De Simone}, Angela and Federico Falchi and Federica Belluti and {Di Martino}, {Rita Maria Concetta} and Silvia Gobbi and Vincenza Andrisano and Andrea Tarozzi and Manuela Bartolini and Andrea Cavalli and Alessandra Bisi",

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doi = "10.1016/j.bmcl.2015.05.002",

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T2 - The role of the amine on the indanone scaffold

AU - Rampa, Angela

AU - Mancini, Francesca

AU - De Simone, Angela

AU - Falchi, Federico

AU - Belluti, Federica

AU - Di Martino, Rita Maria Concetta

AU - Gobbi, Silvia

AU - Andrisano, Vincenza

AU - Tarozzi, Andrea

AU - Bartolini, Manuela

AU - Cavalli, Andrea

AU - Bisi, Alessandra

PY - 2015/6/4

Y1 - 2015/6/4

N2 - In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer's disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC50 = 2.49 ± 0.08 μM), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series.

AB - In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer's disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC50 = 2.49 ± 0.08 μM), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series.

KW - AChE

KW - Alzheimer's disease

KW - BACE1

KW - Drug discovery

KW - Indanone

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U2 - 10.1016/j.bmcl.2015.05.002

DO - 10.1016/j.bmcl.2015.05.002

M3 - Article

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EP - 2808

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 14

ER -

From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold

Abstract

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