Literature DB >> 30108867

Structure-metabolism-relationships in the microsomal clearance of piperazin-1-ylpyridazines.

Sabin Llona-Minguez1, Artin Ghassemian1, Pawel Baranczewski2, Matthieu Desroses1, Tobias Koolmeister1, Per Artursson2, Martin Scobie1, Thomas Helleday1.   

Abstract

In this study, we provide insight into the metabolic profile of a series of piperazin-1-ylpyridazines suffering from rapid in vitro intrinsic clearance in a metabolic stability assay using liver microsomes (e.g. compound 1 MLM/HLM t1/2 = 2/3 min). Aided by empirical metabolite identification and computational predictive models, we designed the structural modifications required to improve in vitro intrinsic clearance by more than 50-fold (e.g. compound 29 MLM/HLM t1/2 = 113/105 min).

Entities:  

Year:  2017        PMID： 30108867      PMCID： PMC6072423          DOI： 10.1039/c7md00230k

Source DB:  PubMed          Journal:  Medchemcomm        ISSN： 2040-2503            Impact factor:   3.597


  15 in total

1.  Similarity searching of chemical databases using atom environment descriptors (MOLPRINT 2D): evaluation of performance.

Authors:  Andreas Bender; Hamse Y Mussa; Robert C Glen; Stephan Reiling
Journal:  J Chem Inf Comput Sci       Date:  2004 Sep-Oct

2.  Reaction site mapping of xenobiotic biotransformations.

Authors:  Scott Boyer; Catrin Hasselgren Arnby; Lars Carlsson; James Smith; Viktor Stein; Robert C Glen
Journal:  J Chem Inf Model       Date:  2007-02-16       Impact factor: 4.956

3.  Identification of Triazolothiadiazoles as Potent Inhibitors of the dCTP Pyrophosphatase 1.

Authors:  Sabin Llona-Minguez; Andreas Höglund; Elisee Wiita; Ingrid Almlöf; André Mateus; José Manuel Calderón-Montaño; Cindy Cazares-Körner; Evert Homan; Olga Loseva; Pawel Baranczewski; Ann-Sofie Jemth; Maria Häggblad; Ulf Martens; Bo Lundgren; Per Artursson; Thomas Lundbäck; Annika Jenmalm Jensen; Ulrika Warpman Berglund; Martin Scobie; Thomas Helleday
Journal:  J Med Chem       Date:  2017-02-15       Impact factor: 7.446

4.  XenoSite: accurately predicting CYP-mediated sites of metabolism with neural networks.

Authors:  Jed Zaretzki; Matthew Matlock; S Joshua Swamidass
Journal:  J Chem Inf Model       Date:  2013-11-23       Impact factor: 4.956

5.  In silico tools for sharing data and knowledge on toxicity and metabolism: derek for windows, meteor, and vitic.

Authors:  Carol A Marchant; Katharine A Briggs; Anthony Long
Journal:  Toxicol Mech Methods       Date:  2008       Impact factor: 2.987

6.  Piperazin-1-ylpyridazine Derivatives Are a Novel Class of Human dCTP Pyrophosphatase 1 Inhibitors.

Authors:  Sabin Llona-Minguez; Andreas Höglund; Artin Ghassemian; Matthieu Desroses; José Manuel Calderón-Montaño; Estefanía Burgos Morón; Nicholas C K Valerie; Elisee Wiita; Ingrid Almlöf; Tobias Koolmeister; André Mateus; Cindy Cazares-Körner; Kumar Sanjiv; Evert Homan; Olga Loseva; Pawel Baranczewski; Masoud Darabi; Amir Mehdizadeh; Shabnam Fayezi; Ann-Sofie Jemth; Ulrika Warpman Berglund; Kristmundur Sigmundsson; Thomas Lundbäck; Annika Jenmalm Jensen; Per Artursson; Martin Scobie; Thomas Helleday
Journal:  J Med Chem       Date:  2017-05-16       Impact factor: 7.446

7.  SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism.

Authors:  Patrik Rydberg; David E Gloriam; Jed Zaretzki; Curt Breneman; Lars Olsen
Journal:  ACS Med Chem Lett       Date:  2010-03-15       Impact factor: 4.345

8.  Discovery of an Oral Potent Selective Inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS).

Authors:  Chris P Carron; John I Trujillo; Kirk L Olson; Wei Huang; Bruce C Hamper; Tom Dice; Bradley E Neal; Matthew J Pelc; Jacqueline E Day; Douglas C Rohrer; James R Kiefer; Joseph B Moon; Barbara A Schweitzer; Tanisha D Blake; Steve R Turner; Rhonda Woerndle; Brenda L Case; Christine P Bono; Vickie M Dilworth; Christie L Funckes-Shippy; Becky L Hood; Gina M Jerome; Christine M Kornmeier; Melissa R Radabaugh; Melanie L Williams; Michael S Davies; Craig D Wegner; Dean J Welsch; William M Abraham; Chad J Warren; Martin E Dowty; Fengmei Hua; Anup Zutshi; Jerry Z Yang; Atli Thorarensen
Journal:  ACS Med Chem Lett       Date:  2010-02-02       Impact factor: 4.345

9.  MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.

Authors:  Helge Gad; Tobias Koolmeister; Ann-Sofie Jemth; Saeed Eshtad; Sylvain A Jacques; Cecilia E Ström; Linda M Svensson; Niklas Schultz; Thomas Lundbäck; Berglind Osk Einarsdottir; Aljona Saleh; Camilla Göktürk; Pawel Baranczewski; Richard Svensson; Ronnie P-A Berntsson; Robert Gustafsson; Kia Strömberg; Kumar Sanjiv; Marie-Caroline Jacques-Cordonnier; Matthieu Desroses; Anna-Lena Gustavsson; Roger Olofsson; Fredrik Johansson; Evert J Homan; Olga Loseva; Lars Bräutigam; Lars Johansson; Andreas Höglund; Anna Hagenkort; Therese Pham; Mikael Altun; Fabienne Z Gaugaz; Svante Vikingsson; Bastiaan Evers; Martin Henriksson; Karl S A Vallin; Olov A Wallner; Lars G J Hammarström; Elisee Wiita; Ingrid Almlöf; Christina Kalderén; Hanna Axelsson; Tatjana Djureinovic; Jordi Carreras Puigvert; Maria Häggblad; Fredrik Jeppsson; Ulf Martens; Cecilia Lundin; Bo Lundgren; Ingrid Granelli; Annika Jenmalm Jensen; Per Artursson; Jonas A Nilsson; Pål Stenmark; Martin Scobie; Ulrika Warpman Berglund; Thomas Helleday
Journal:  Nature       Date:  2014-04-02       Impact factor: 49.962

Review 10.  The metabolism of alicyclic amines to reactive iminium ion intermediates.

Authors:  J W Gorrod; G Aislaitner
Journal:  Eur J Drug Metab Pharmacokinet       Date:  1994 Jul-Sep       Impact factor: 2.441
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