Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery.

Literature DB >> 24900744

Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery.

Werngard Czechtizky¹, Jüergen Dedio¹, Bimbisar Desai², Karen Dixon², Elizabeth Farrant², Qixing Feng², Trevor Morgan², David M Parry², Manoj K Ramjee², Christopher N Selway², Thorsten Schmidt¹, Gary J Tarver², Adrian G Wright².

Abstract

A novel integrated discovery platform has been used to synthesize and biologically assay a series of xanthine-derived dipeptidyl peptidase 4 (DPP4) antagonists. Design, synthesis, purification, quantitation, dilution, and bioassay have all been fully integrated to allow continuous automated operation. The system has been validated against a set of known DPP4 inhibitors and shown to give excellent correlation between traditional medicinal chemistry generated biological data and platform data. Each iterative loop of synthesis through biological assay took two hours in total, demonstrating rapid iterative structure-activity relationship generation.

Entities: Chemical Gene

Keywords: Closed loop drug design; DPP4; automated drug discovery; flow synthesis

Year: 2013 PMID： 24900744 PMCID： PMC4027231 DOI： 10.1021/ml400171b

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

5 in total

1. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes.

Authors: Matthias Eckhardt; Elke Langkopf; Michael Mark; Moh Tadayyon; Leo Thomas; Herbert Nar; Waldemar Pfrengle; Brian Guth; Ralf Lotz; Peter Sieger; Holger Fuchs; Frank Himmelsbach
Journal: J Med Chem Date: 2007-12-01 Impact factor: 7.446

2. Application of parallel gradient high performance liquid chromatography with ultra-violet, evaporative light scattering and electrospray mass spectrometric detection for the quantitative quality control of the compound file to support pharmaceutical discovery.

Authors: Anthony W Squibb; Mark R Taylor; Barry L Parnas; Gareth Williams; Richard Girdler; Peter Waghorn; Adrian G Wright; Frank S Pullen
Journal: J Chromatogr A Date: 2007-11-13 Impact factor: 4.759

3. Rapid discovery of a novel series of Abl kinase inhibitors by application of an integrated microfluidic synthesis and screening platform.

Authors: Bimbisar Desai; Karen Dixon; Elizabeth Farrant; Qixing Feng; Karl R Gibson; Willem P van Hoorn; James Mills; Trevor Morgan; David M Parry; Manoj K Ramjee; Christopher N Selway; Gary J Tarver; Gavin Whitlock; Adrian G Wright
Journal: J Med Chem Date: 2013-03-25 Impact factor: 7.446

4. Automated Lead Optimization of MMP-12 Inhibitors Using a Genetic Algorithm.

Authors: Stephen D Pickett; Darren V S Green; David L Hunt; David A Pardoe; Ian Hughes
Journal: ACS Med Chem Lett Date: 2010-10-20 Impact factor: 4.345

5. Online fluorescence enhancement assay for the acetylcholine binding protein with parallel mass spectrometric identification.

Authors: Jeroen Kool; Gerdien E de Kloe; Ben Bruyneel; Jon S de Vlieger; Kim Retra; Maikel Wijtmans; Rene van Elk; August B Smit; Rob Leurs; Henk Lingeman; Iwan J P de Esch; Hubertus Irth
Journal: J Med Chem Date: 2010-06-24 Impact factor: 7.446

5 in total

12 in total

1. Closing the Loop: Developing an Integrated Design, Make, and Test Platform for Discovery.

Authors: David M Parry
Journal: ACS Med Chem Lett Date: 2019-05-15 Impact factor: 4.345

2. Integrated Platform for Expedited Synthesis-Purification-Testing of Small Molecule Libraries.

Authors: Aleksandra Baranczak; Noah P Tu; Jasmina Marjanovic; Philip A Searle; Anil Vasudevan; Stevan W Djuric
Journal: ACS Med Chem Lett Date: 2017-03-28 Impact factor: 4.345

Review 3. Expanding the medicinal chemistry synthetic toolbox.

Authors: Jonas Boström; Dean G Brown; Robert J Young; György M Keserü
Journal: Nat Rev Drug Discov Date: 2018-08-24 Impact factor: 84.694

4. Selective Phenylimidazole-Based Inhibitors of the Mycobacterium tuberculosis Proteasome.

Authors: Wenhu Zhan; Hao-Chi Hsu; Trevor Morgan; Tierra Ouellette; Kristin Burns-Huang; Ryoma Hara; Adrian G Wright; Toshihiro Imaeda; Rei Okamoto; Kenjiro Sato; Mayako Michino; Manoj Ramjee; Kazuyoshi Aso; Peter T Meinke; Michael Foley; Carl F Nathan; Huilin Li; Gang Lin
Journal: J Med Chem Date: 2019-10-15 Impact factor: 7.446

Review 5. Automating drug discovery.

Authors: Gisbert Schneider
Journal: Nat Rev Drug Discov Date: 2017-12-15 Impact factor: 84.694

6. Latest QSAR study of adenosine Α₂Β receptor affinity of xanthines and deazaxanthines.

Authors: Alfonso Pérez-Garrido; Virginia Rivero-Buceta; Gaspar Cano; Sanjay Kumar; Horacio Pérez-Sánchez; Marta Teijeira Bautista
Journal: Mol Divers Date: 2015-07-10 Impact factor: 2.943

7. Scaffold-based design of xanthine as highly potent inhibitors of DPP-IV for improving glucose homeostasis in DIO mice.

Authors: Yan Ran; Heying Pei; Caifeng Xie; Liang Ma; Yuzhe Wu; Kai Lei; Mingfeng Shao; Minghai Tang; Mingli Xiang; Aihua Peng; Yuquan Wei; Lijuan Chen
Journal: Mol Divers Date: 2015-02-12 Impact factor: 2.943