Document Detail


Discovery of 2-(Cyclohexylmethyl-amino)-pyrimidines as a New Class of Reversible Valosine Containing Protein Inhibitors.
MedLine Citation:
PMID:  25474526     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Valosine-containing protein (VCP), also known as p97 or cdc48 in yeast, is a highly abundant protein belonging to the AAA ATPase family involved a number of essential cellular functions, including ubiquitin-proteasome mediated protein degradation, Golgi reassembly, transcription activation and cell cycle control. Altered expression of VCP has been detected in many cancer types sometime associated with poor prognosis. Furthermore VCP mutations are causative of some neurodegenerative disorders. In this paper we report the discovery, synthesis and structure-activity relationships of substituted 2-amino-pyrimidines, representing a new class of reversible VCP inhibitors. This class of compounds, identified in a HTS campaign against recombinant VCP, has been progressively expanded and manipulated to increase biochemical potency and gain cellular activity.
Authors:
Giovanni Cervi; Paola Magnaghi; Daniela Asa; Nilla Avanzi; Alessandra Badari; Daniela Borghi; Michele Caruso; Alessandra Cirla; Liviana Cozzi; Eduard R Felder; Arturo Galvani; Fabio Gasparri; Antonio Lomolino; Steven Magnuson; Beatrice Malgesini; Ilaria Motto; Maurizio Pasi; Simona Rizzi; Barbara Salom; Graziella Sorrentino; Sonia Troiani; Barbara Valsasina; Thomas O'Brien; Antonella Isacchi; Daniele Donati; Roberto D'Alessio
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-4
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-4     Completed Date:  -     Revised Date:  2014-12-5    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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