Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2017 Nov 1;27(21):4812-4816. doi: 10.1016/j.bmcl.2017.09.058. Epub 2017 Sep 28.

Sulfonamido-derivatives of unsubstituted carbazoles as BACE1 inhibitors.

Author information

1
Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy. Electronic address: simone.bertini@unipi.it.
2
Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
3
Molecular Modeling Section (MMS), Dipartimento di Scienze del Farmaco, Università di Padova, Via Marzolo 5, I-35131 Padova, Italy.

Abstract

A novel series of variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylsulfonamides has been synthesized and assayed for β-Secretase (BACE1) inhibitory activity. BACE1 is a widely recognized drug target for the prevention and treatment of Alzheimer's Disease (AD). The introduction of benzyl substituents on the nitrogen atom of the arylsulfonamide moiety has so far led to the best results, with three derivatives showing IC50 values ranging from 1.6 to 1.9 μM. Therefore, a significant improvement over the previously reported series of N-carboxamides (displaying IC50's ≥ 2.5 μM) has been achieved, thus suggesting an active role of the sulfonamido-portion in the inhibition process. Preliminary molecular modeling studies have been carried out to rationalize the observed structure-activity relationships.

KEYWORDS:

Alzheimer; BACE1; Carbazole; Molecular docking; Sulfonamides

PMID:
28993050
DOI:
10.1016/j.bmcl.2017.09.058
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center