Structure-based optimization of potent PDK1 inhibitors

Mauro Angiolini; Patrizia Banfi; Elena Casale; Francesco Casuscelli; Claudio Fiorelli; Maria B. Saccardo; Marco Silvagni; Fabio Zuccotto

doi:10.1016/j.bmcl.2010.05.070

Structure-based optimization of potent PDK1 inhibitors

Mauro Angiolini (Lead / Corresponding author)
, Patrizia Banfi
, Elena Casale
, Francesco Casuscelli
, Claudio Fiorelli
, Maria B. Saccardo
, Marco Silvagni
, Fabio Zuccotto

Drug Discovery Unit

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

In this Letter is described the structure-based design of potent dihydro-pyrazoloquinazolines as PDK1 inhibitors. Starting from low potency HTS hits with the aid of X-ray crystallography and modeling, a medicinal chemistry activity was carried out to improve potency versus PDK1 and selectivity versus CDK2 protein kinase.

Original language	English
Pages (from-to)	4095-4099
Number of pages	5
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	20
Issue number	14
Early online date	8 Jun 2010
DOIs	https://doi.org/10.1016/j.bmcl.2010.05.070
Publication status	Published - 15 Jul 2010

Keywords

CDK2
Kinase
PDK1
Scaffold
Structure-based drug design

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Organic Chemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry
Biochemistry

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10.1016/j.bmcl.2010.05.070

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title = "Structure-based optimization of potent PDK1 inhibitors",

abstract = "In this Letter is described the structure-based design of potent dihydro-pyrazoloquinazolines as PDK1 inhibitors. Starting from low potency HTS hits with the aid of X-ray crystallography and modeling, a medicinal chemistry activity was carried out to improve potency versus PDK1 and selectivity versus CDK2 protein kinase.",

keywords = "CDK2, Kinase, PDK1, Scaffold, Structure-based drug design",

author = "Mauro Angiolini and Patrizia Banfi and Elena Casale and Francesco Casuscelli and Claudio Fiorelli and Saccardo, \{Maria B.\} and Marco Silvagni and Fabio Zuccotto",

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T1 - Structure-based optimization of potent PDK1 inhibitors

AU - Angiolini, Mauro

AU - Banfi, Patrizia

AU - Casale, Elena

AU - Casuscelli, Francesco

AU - Fiorelli, Claudio

AU - Saccardo, Maria B.

AU - Silvagni, Marco

AU - Zuccotto, Fabio

PY - 2010/7/15

Y1 - 2010/7/15

N2 - In this Letter is described the structure-based design of potent dihydro-pyrazoloquinazolines as PDK1 inhibitors. Starting from low potency HTS hits with the aid of X-ray crystallography and modeling, a medicinal chemistry activity was carried out to improve potency versus PDK1 and selectivity versus CDK2 protein kinase.

AB - In this Letter is described the structure-based design of potent dihydro-pyrazoloquinazolines as PDK1 inhibitors. Starting from low potency HTS hits with the aid of X-ray crystallography and modeling, a medicinal chemistry activity was carried out to improve potency versus PDK1 and selectivity versus CDK2 protein kinase.

KW - CDK2

KW - Kinase

KW - PDK1

KW - Scaffold

KW - Structure-based drug design

UR - https://www.scopus.com/pages/publications/77953872158

U2 - 10.1016/j.bmcl.2010.05.070

DO - 10.1016/j.bmcl.2010.05.070

M3 - Article

C2 - 20621725

AN - SCOPUS:77953872158

SN - 0960-894X

VL - 20

SP - 4095

EP - 4099

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 14

ER -

Structure-based optimization of potent PDK1 inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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