Literature DB >> 31749905

Scaffold Morphing Identifies 3-Pyridyl Azetidine Ureas as Inhibitors of Nicotinamide Phosphoribosyltransferase (NAMPT).

Daniel S Palacios1, Erik L Meredith1, Toshio Kawanami1, Christopher M Adams1, Xin Chen1, Veronique Darsigny1, Mark Palermo1, Daniel Baird2, Elizabeth L George2, Chantale Guy2, Jeffrey Hewett2, Laryssa Tierney2, Sachin Thigale2, Louis Wang2, Wilhelm A Weihofen2.   

Abstract

Small molecules that inhibit the metabolic enzyme NAMPT have emerged as potential therapeutics in oncology. As part of our effort in this area, we took a scaffold morphing approach and identified 3-pyridyl azetidine ureas as a potent NAMPT inhibiting motif. We explored the SAR of this series, including 5 and 6 amino pyridines, using a convergent synthetic strategy. This lead optimization campaign yielded multiple compounds with excellent in vitro potency and good ADME properties that culminated in compound 27.
Copyright © 2019 American Chemical Society.

Entities:  

Year:  2019        PMID： 31749905      PMCID： PMC6862340          DOI： 10.1021/acsmedchemlett.9b00325

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


  15 in total

1.  Nicotinamide phosphoribosyl transferase/pre-B cell colony-enhancing factor/visfatin is required for lymphocyte development and cellular resistance to genotoxic stress.

Authors:  Anthony Rongvaux; Mara Galli; Sébastien Denanglaire; Frédéric Van Gool; Pierre L Drèze; Claude Szpirer; Fabrice Bureau; Fabienne Andris; Oberdan Leo
Journal:  J Immunol       Date:  2008-10-01       Impact factor: 5.422

2.  Preclinical models of nicotinamide phosphoribosyltransferase inhibitor-mediated hematotoxicity and mitigation by co-treatment with nicotinic acid.

Authors:  Jacqueline M Tarrant; Preeti Dhawan; Jatinder Singh; Tanja S Zabka; Emer Clarke; Garry DosSantos; Peter S Dragovich; Deepak Sampath; Tori Lin; Bobbi McCray; Nghi La; Trung Nguyen; Ariel Kauss; Donna Dambach; Dinah L Misner; Dolores Diaz; Hirdesh Uppal
Journal:  Toxicol Mech Methods       Date:  2015-04-20       Impact factor: 2.987

3.  Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase.

Authors:  Tanja S Zabka; Jatinder Singh; Preeti Dhawan; Bianca M Liederer; Jason Oeh; Mara A Kauss; Yang Xiao; Mark Zak; Tori Lin; Bobbi McCray; Nghi La; Trung Nguyen; Joseph Beyer; Cynthia Farman; Hirdesh Uppal; Peter S Dragovich; Thomas O'Brien; Deepak Sampath; Dinah L Misner
Journal:  Toxicol Sci       Date:  2014-12-11       Impact factor: 4.849

4.  The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells.

Authors:  Javier R Revollo; Andrew A Grimm; Shin-ichiro Imai
Journal:  J Biol Chem       Date:  2004-09-20       Impact factor: 5.157

Review 5.  Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as therapeutics: rationales, controversies, clinical experience.

Authors:  Fabrizio Montecucco; Michele Cea; Inga Bauer; Debora Soncini; Irene Caffa; Denise Lasigliè; Aimable Nahimana; Antonio Uccelli; Santina Bruzzone; Alessio Nencioni
Journal:  Curr Drug Targets       Date:  2013-06-01       Impact factor: 3.465

Review 6.  Medicinal chemistry of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors.

Authors:  Ubaldina Galli; Cristina Travelli; Alberto Massarotti; Gohar Fakhfouri; Reza Rahimian; Gian Cesare Tron; Armando A Genazzani
Journal:  J Med Chem       Date:  2013-05-31       Impact factor: 7.446

Review 7.  Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition.

Authors:  Katrina L Bogan; Charles Brenner
Journal:  Annu Rev Nutr       Date:  2008       Impact factor: 11.848

8.  NAD as a genotype-specific drug target.

Authors:  Szu-Chieh Mei; Charles Brenner
Journal:  Chem Biol       Date:  2013-11-21

9.  Discovery of potent and efficacious urea-containing nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with reduced CYP2C9 inhibition properties.

Authors:  Janet Gunzner-Toste; Guiling Zhao; Paul Bauer; Timm Baumeister; Alexandre J Buckmelter; Maureen Caligiuri; Karl H Clodfelter; Bang Fu; Bingsong Han; Yen-Ching Ho; Nikolai Kley; Xiaorong Liang; Bianca M Liederer; Jian Lin; Sophie Mukadam; Thomas O'Brien; Angela Oh; Dominic J Reynolds; Geeta Sharma; Nicholas Skelton; Chase C Smith; Jasleen Sodhi; Weiru Wang; Zhongguo Wang; Yang Xiao; Po-wai Yuen; Mark Zak; Lei Zhang; Xiaozhang Zheng; Kenneth W Bair; Peter S Dragovich
Journal:  Bioorg Med Chem Lett       Date:  2013-04-25       Impact factor: 2.823

10.  Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody-Drug Conjugates.

Authors:  Alexei S Karpov; Tinya Abrams; Suzanna Clark; Ankita Raikar; Joseph A D'Alessio; Michael P Dillon; Thomas G Gesner; Darryl Jones; Marion Lacaud; William Mallet; Piotr Martyniuk; Erik Meredith; Morvarid Mohseni; Cristina M Nieto-Oberhuber; Daniel Palacios; Francesca Perruccio; Grazia Piizzi; Mauro Zurini; Carl Uli Bialucha
Journal:  ACS Med Chem Lett       Date:  2018-06-28       Impact factor: 4.345
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  3 in total

Review 1.  Put a ring on it: application of small aliphatic rings in medicinal chemistry.

Authors:  Matthias R Bauer; Paolo Di Fruscia; Simon C C Lucas; Iacovos N Michaelides; Jennifer E Nelson; R Ian Storer; Benjamin C Whitehurst
Journal:  RSC Med Chem       Date:  2021-01-07

Review 2.  From Rate-Limiting Enzyme to Therapeutic Target: The Promise of NAMPT in Neurodegenerative Diseases.

Authors:  Yumeng Zhu; Ping Xu; Xuan Huang; Wen Shuai; Li Liu; Shuai Zhang; Rui Zhao; Xiuying Hu; Guan Wang
Journal:  Front Pharmacol       Date:  2022-07-12       Impact factor: 5.988

Review 3.  Nicotinamide Adenine Dinucleotide (NAD) Metabolism as a Relevant Target in Cancer.

Authors:  Lola E Navas; Amancio Carnero
Journal:  Cells       Date:  2022-08-24       Impact factor: 7.666
  3 in total

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