Pharmacophore elucidation of phosphoiodyn A - Potent and selective peroxisome proliferator-activated receptor β/δ agonists with neuroprotective activity.
作者： Nihar Kinarivala , Ji Ho Suh , Mina Botros , Paul Webb , Paul C. Trippier
DOI: 10.1016/J.BMCL.2016.03.028
关键词:
摘要: We report the pharmacophore of peroxisome proliferator-activated receptor δ (PPARδ) agonist natural product phosphoiodyn A is phosphonate core. Synthesis simplified esters 13 and 15 provide structurally novel, highly selective potent PPARδ agonists (EC50=78 112 nM, respectively). Further, both compounds demonstrate significant neuroprotective activity in an vitro cellular model indicating that phosphonates may be effective novel scaffold for design therapeutics treatment neurodegenerative disorders.
sci-hub.se 参考文章(28)
Henry Krum, Richard E Gilbert, David L Prior, Kim A Connelly, Yuan Zhang, Darren A Kelly, Abstract 3922: Inhibition of PKC Beta by Ruboxistaurin Preserves Cardiac Function and Reduces Extracellular Matrix Production in Diabetic Cardiomyopathy Circulation. ,vol. 114, pp. 843- 843 ,(2006)
Cristina Malagelada Grau, Lloyd A. Greene, Use of PC12 Cells and Rat Superior Cervical Ganglion Sympathetic Neurons as Models for Neuroprotective Assays Relevant to Parkinson’s Disease Neurotrophic Factors. ,vol. 846, pp. 201- 211 ,(2012) , 10.1007/978-1-61779-536-7_18
Shogo Sakuma, Tsuyoshi Endo, Takashi Kanda, Hideki Nakamura, Satomi Yamasaki, Tomio Yamakawa, Synthesis of a novel human PPARδ selective agonist and its stimulatory effect on oligodendrocyte differentiation. Bioorganic & Medicinal Chemistry Letters. ,vol. 21, pp. 240- 244 ,(2011) , 10.1016/J.BMCL.2010.11.030
Hiroki Fujieda, Shinya Usui, Takayoshi Suzuki, Hidehiko Nakagawa, Michitaka Ogura, Makoto Makishima, Naoki Miyata, Phenylpropanoic acid derivatives bearing a benzothiazole ring as PPARδ-selective agonists Bioorganic & Medicinal Chemistry Letters. ,vol. 17, pp. 4351- 4357 ,(2007) , 10.1016/J.BMCL.2007.05.017
Rajnish K. Chaturvedi, M. Flint Beal, PPAR: a therapeutic target in Parkinsons disease Journal of Neurochemistry. ,vol. 106, pp. 506- 518 ,(2008) , 10.1111/J.1471-4159.2008.05388.X
Reinhardt B. Baudy, John A. Butera, Magid A. Abou-Gharbia, Hong Chen, Boyd Harrison, Uday Jain, Ronald Magolda, Jean Y. Sze, Michael R. Brandt, Terri A. Cummons, Diane Kowal, Menelas N. Pangalos, Bojana Zupan, Matthew Hoffmann, Michael May, Cheryl Mugford, Jeffrey Kennedy, Wayne E. Childers, Prodrugs of perzinfotel with improved oral bioavailability. Journal of Medicinal Chemistry. ,vol. 52, pp. 771- 778 ,(2009) , 10.1021/JM8011799
Shweta Mandrekar-Colucci, Andrew Sauerbeck, Phillip G. Popovich, Dana M. McTigue, PPAR agonists as therapeutics for CNS trauma and neurological diseases. Asn Neuro. ,vol. 5, ,(2013) , 10.1042/AN20130030
Jeffrey M. Peters, Yatrik M. Shah, Frank J. Gonzalez, The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention Nature Reviews Cancer. ,vol. 12, pp. 181- 195 ,(2012) , 10.1038/NRC3214
Stefan Weigand, Hilmar Bischoff, Elke Dittrich-Wengenroth, Heike Heckroth, Dieter Lang, Andrea Vaupel, Michael Woltering, Minor structural modifications convert a selective PPARα agonist into a potent, highly selective PPARδ agonist Bioorganic & Medicinal Chemistry Letters. ,vol. 15, pp. 4619- 4623 ,(2005) , 10.1016/J.BMCL.2005.06.023
Y. Guan, Y. Zhang, M.D. Breyer, The Role of PPARs in the Transcriptional Control of Cellular Processes. Drug News & Perspectives. ,vol. 15, pp. 147- 154 ,(2002) , 10.1358/DNP.2002.15.3.840011