Literature DB >> 24900882

Pivotal Role of an Aliphatic Side Chain in the Development of an HDM2 Inhibitor.

Yao Ma1, Brian R Lahue1, Craig R Gibeau1, Gerald W Shipps1, Stéphane L Bogen2, Yaolin Wang2, Zhuyan Guo2, Timothy J Guzi1.   

Abstract

Introduction of an aliphatic side chain to a key position of a novel piperidine-based HDM2 inhibitor scaffold resulted in significant potency gains, enabling further series progression.

Entities:  

Keywords:  HDM2; MDM2; p53; protein−protein interaction; small molecule inhibitor; substituted piperidine

Year:  2014        PMID： 24900882      PMCID： PMC4027732          DOI： 10.1021/ml500019s

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  22 in total

1.  An efficient synthesis of a dual PPAR alpha/gamma agonist and the formation of a sterically congested alpha-aryloxyisobutyric acid via a Bargellini reaction.

Authors:  Raymond J Cvetovich; John Y L Chung; Michael H Kress; Joseph S Amato; Louis Matty; M David Weingarten; Fuh-Rong Tsay; Zhen Li; George Zhou
Journal:  J Org Chem       Date:  2005-10-14       Impact factor: 4.354

2.  Substituted piperidines as HDM2 inhibitors.

Authors:  Yao Ma; Brian R Lahue; Gerald W Shipps; Jeseca Brookes; Yaolin Wang
Journal:  Bioorg Med Chem Lett       Date:  2014-01-17       Impact factor: 2.823

3.  Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain.

Authors:  P H Kussie; S Gorina; V Marechal; B Elenbaas; J Moreau; A J Levine; N P Pavletich
Journal:  Science       Date:  1996-11-08       Impact factor: 47.728

4.  mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein.

Authors:  J Chen; X Wu; J Lin; A J Levine
Journal:  Mol Cell Biol       Date:  1996-05       Impact factor: 4.272

Review 5.  MDM2--master regulator of the p53 tumor suppressor protein.

Authors:  J Momand; H H Wu; G Dasgupta
Journal:  Gene       Date:  2000-01-25       Impact factor: 3.688

6.  HDM2 protein overexpression, but not gene amplification, is related to tumorigenesis of cutaneous melanoma.

Authors:  D Polsky; B C Bastian; C Hazan; K Melzer; J Pack; A Houghton; K Busam; C Cordon-Cardo; I Osman
Journal:  Cancer Res       Date:  2001-10-15       Impact factor: 12.701

7.  Fluorescence polarization assay and inhibitor design for MDM2/p53 interaction.

Authors:  Rumin Zhang; Todd Mayhood; Philip Lipari; Yaolin Wang; James Durkin; Rosalinda Syto; Jennifer Gesell; Charles McNemar; William Windsor
Journal:  Anal Biochem       Date:  2004-08-01       Impact factor: 3.365

Review 8.  Small molecule inhibitors of the p53-MDM2.

Authors:  Chun-Qi Hu; Yong-Zhou Hu
Journal:  Curr Med Chem       Date:  2008       Impact factor: 4.530

9.  Synthesis and pharmacological evaluation of some 6-substituted 7-methyl-1,4-dioxa-7-azaspiro[4.5]decanes as potential dopamine agonists.

Authors:  A N Brubaker; M Colley
Journal:  J Med Chem       Date:  1986-08       Impact factor: 7.446

Review 10.  The MDM2 gene amplification database.

Authors:  J Momand; D Jung; S Wilczynski; J Niland
Journal:  Nucleic Acids Res       Date:  1998-08-01       Impact factor: 16.971
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  5 in total

Review 1.  Chemical modulation of transcription factors.

Authors:  Bianca Wiedemann; Jörn Weisner; Daniel Rauh
Journal:  Medchemcomm       Date:  2018-07-11       Impact factor: 3.597

2.  Discovery of Novel 3,3-Disubstituted Piperidines as Orally Bioavailable, Potent, and Efficacious HDM2-p53 Inhibitors.

Authors:  Stéphane L Bogen; Weidong Pan; Craig R Gibeau; Brian R Lahue; Yao Ma; Latha G Nair; Elise Seigel; Gerald W Shipps; Yuan Tian; Yaolin Wang; Yinghui Lin; Ming Liu; Suxing Liu; Asra Mirza; Xiaoying Wang; Philip Lipari; Cynthia Seidel-Dugan; Daniel J Hicklin; W Robert Bishop; Diane Rindgen; Amin Nomeir; Winifred Prosise; Paul Reichert; Giovanna Scapin; Corey Strickland; Ronald J Doll
Journal:  ACS Med Chem Lett       Date:  2016-01-20       Impact factor: 4.345

3.  Activity-Directed Synthesis of Inhibitors of the p53/hDM2 Protein-Protein Interaction.

Authors:  Adam I Green; Fruzsina Hobor; Christopher P Tinworth; Stuart Warriner; Andrew J Wilson; Adam Nelson
Journal:  Chemistry       Date:  2020-08-04       Impact factor: 5.236

Review 4.  Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.

Authors:  Yujun Zhao; Angelo Aguilar; Denzil Bernard; Shaomeng Wang
Journal:  J Med Chem       Date:  2014-11-14       Impact factor: 7.446

Review 5.  Chemical Variations on the p53 Reactivation Theme.

Authors:  Carlos J A Ribeiro; Cecília M P Rodrigues; Rui Moreira; Maria M M Santos
Journal:  Pharmaceuticals (Basel)       Date:  2016-05-13
  5 in total

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