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Inhibitors of diacylglycerol acyltransferase: a review of 2008 patents

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Pages 19-29 | Published online: 20 Dec 2009

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Vishal P. Zambre, Shamali M. Khamkar, Dnyaneshwar D. Gavhane, Sagar C. Khedkar, Monali R. Chavan, Madhuri M. Pandey, Sonali B. Sanap, Rajesh B. Patil & Sanjay D. Sawant. (2020) Patent landscape for discovery of promising acyltransferase DGAT and MGAT inhibitors. Expert Opinion on Therapeutic Patents 30:11, pages 873-896.
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Dong Jin Hong, Seung Hyun Jung, Jisook Kim, Danbee Jung, Young Gil Ahn, Kwee Hyun Suh & Kyung Hoon Min. (2020) Synthesis and biological evaluation of novel thienopyrimidine derivatives as diacylglycerol acyltransferase 1 (DGAT-1) inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry 35:1, pages 227-234.
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Daisuke Matsuda & Hiroshi Tomoda. (2010) Triazolo compounds useful as diacylglycerol acyltransferase1 inhibitor – WO2009126624. Expert Opinion on Therapeutic Patents 20:8, pages 1097-1102.
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Articles from other publishers (23)

Masoumeh Khalifeh, Raul D. Santos, Reza Kazemi Oskuee, Ali Badiee, Seyed Hamid Aghaee-Bakhtiari & Amirhossein Sahebkar. (2023) A novel regulatory facet for hypertriglyceridemia: The role of microRNAs in the regulation of triglyceride-rich lipoprotein biosynthesis. Progress in Lipid Research 89, pages 101197.
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Summon Koul, Suresh Kurhade, Sandeep Bhosale, Keshav Naik, Videsh Salunkhe, Sudhir Ravula, Prasad Punde, Ravikumar Velayutham, Atul Tiwari, Daniela Ahl, Srividya Malkapuram, Vamsi Mudagala, Amol Raje, Dhananjay Umrani, Suhas Tambe, Poonam Patil, Umesh Singh, Debnath Bhuniya, Narayanan Hariharan & Kasim Mookhtiar. (2022) Design and synthesis of novel spirocyclic carboxylic acids as potent and orally bioavailable DGAT1 inhibitors and their biological evaluation. Bioorganic & Medicinal Chemistry Letters 62, pages 128632.
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Sabrin R. M. Ibrahim, Alaa Sirwi, Basma G. Eid, Shaimaa G. A. Mohamed & Gamal A. Mohamed. (2021) Fungal Depsides—Naturally Inspiring Molecules: Biosynthesis, Structural Characterization, and Biological Activities. Metabolites 11:10, pages 683.
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Mingliang Zhang, Xiaomin Nie, Yeqing Yuan, Yansu Wang, Xiaojing Ma, Jun Yin & Yuqian Bao. (2021) Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A. International Journal of Endocrinology 2021, pages 1-10.
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Yang Yu, Zhicai Wu, Zhi-Cai Shi, Shuwen He, Zhong Lai, Timothy A. Cernak, Petr Vachal, Min Liu, Jian Liu, Qingmei Hong, Tianying Jian, Deodial Guiadeen, Arto Krikorian, Donald M. Sperbeck, Andreas Verras, Lisa M. Sonatore, Beth A. Murphy, Judyann Wiltsie, Christine C. Chung, Judith N. Gorski, Jinqi Liu, Jianying Xiao, Michael Wolff, Sharon X. Tong, Maria Madeira, Bindhu V. Karanam, Dong-Ming Shen, James M. Balkovec, Robert J. De Vita, Shirly Pinto & Ravi P. Nargund. (2019) Accelerating the discovery of DGAT1 inhibitors through the application of parallel medicinal chemistry (PMC). Bioorganic & Medicinal Chemistry Letters 29:11, pages 1380-1385.
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Jianwei Yan, Gaihong Wang, Xiangyu Dang, Binbin Guo, Wuhong Chen, Ting Wang, Limin Zeng, Heyao Wang & Youhong Hu. (2017) Discovery of a low-systemic-exposure DGAT-1 inhibitor with a picolinoylpyrrolidine-2-carboxylic acid moiety. Bioorganic & Medicinal Chemistry 25:17, pages 4701-4714.
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Lin Li, Cun-Long Zhang, Hong-Rui Song, Chun-Yan Tan, Huai-Wei Ding & Yu-Yang Jiang. (2016) Discovery of novel dual inhibitors of VEGFR and PI3K kinases containing 2-ureidothiazole scaffold. Chinese Chemical Letters 27:1, pages 1-6.
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Ravi Naik, Brice W. Obiang-Obounou, Minkyoung Kim, Yongseok Choi, Hyun Sun Lee & Kyeong Lee. (2014) Therapeutic Strategies for Metabolic Diseases: Small-Molecule Diacylglycerol Acyltransferase (DGAT) Inhibitors. ChemMedChem 9:11, pages 2410-2424.
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Gang Zhou, Nicolas Zorn, Pauline Ting, Robert Aslanian, Mingxiang Lin, John Cook, Jean Lachowicz, Albert Lin, Michelle Smith, Joyce Hwa, Margaret van Heek & Scott Walker. (2014) Development of Novel Benzomorpholine Class of Diacylglycerol Acyltransferase I Inhibitors. ACS Medicinal Chemistry Letters 5:5, pages 544-549.
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Brian M. Fox, Kazuyuki Sugimoto, Kiyosei Iio, Atsuhito Yoshida, Jian (Ken) Zhang, Kexue Li, Xiaolin Hao, Marc Labelle, Marie-Louise Smith, Steven M. Rubenstein, Guosen Ye, Dustin McMinn, Simon Jackson, Rebekah Choi, Bei Shan, Ji Ma, Shichang Miao, Takuya Matsui, Nobuya Ogawa, Masahiro Suzuki, Akio Kobayashi, Hidekazu Ozeki, Chihiro Okuma, Yukihito Ishii, Daisuke Tomimoto, Noboru Furakawa, Masahiro Tanaka, Mutsuyoshi Matsushita, Mitsuru Takahashi, Takashi Inaba, Shoichi Sagawa & Frank Kayser. (2014) Discovery of 6-Phenylpyrimido[4,5- b ][1,4]oxazines as Potent and Selective Acyl CoA:Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitors with in Vivo Efficacy in Rodents . Journal of Medicinal Chemistry 57:8, pages 3464-3483.
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Gang Zhou, Pauline C. Ting, Grant Wishart, Nicolas Zorn, Robert G. Aslanian, Mingxiang Lin, Michelle Smith, Scott S. Walker, John Cook, Margaret Van Heek & Jean Lachowicz. (2014) Discovery of novel quinoline carboxylic acid series as DGAT1 inhibitors. Bioorganic & Medicinal Chemistry Letters 24:7, pages 1790-1794.
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Hyunjin M. Kim, Michelle D. Smith, Jae-Hun Kim, Mary Ann Caplen, Tin Yau Chan, Brian A. McKittrick, John A. Cook, Margaret van Heek & Jean Lachowicz. (2013) Identification of 2-aminooxazole amides as acyl-CoA: Diacylglycerol acyltransferase 1 (DGAT1) inhibitors through scaffold hopping strategy. Bioorganic & Medicinal Chemistry Letters 23:23, pages 6410-6414.
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Robert L. Dow, Melissa P. Andrews, Jian-Cheng Li, E. Michael Gibbs, Angel Guzman-Perez, Jennifer L. LaPerle, Qifang Li, Dawn Mather, Michael J. Munchhof, Mark Niosi, Leena Patel, Christian Perreault, Susan Tapley & William J. Zavadoski. (2013) Defining the key pharmacophore elements of PF-04620110: Discovery of a potent, orally-active, neutral DGAT-1 inhibitor. Bioorganic & Medicinal Chemistry 21:17, pages 5081-5097.
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Shuwen He, Qingmei Hong, Zhong Lai, Zhicai Wu, Yang Yu, David W. Kim, Pauline C. Ting, Jeffrey T. Kuethe, Ginger X. Yang, Tianying Jian, Jian Liu, Deodial Guiadeen, Arto D. Krikorian, Donald M. Sperbeck, Lisa M. Sonatore, Judyann Wiltsie, Christine C. Chung, Jack T. Gibson, JeanMarie Lisnock, Beth A. Murphy, Judith N. Gorski, Jinqi Liu, Dunlu Chen, Xiaoli Chen, Michael Wolff, Sharon X. Tong, Maria Madeira, Bindhu V. Karanam, Dong-Ming Shen, James M. Balkovec, Shirly Pinto, Ravi P. Nargund & Robert J. DeVita. (2013) Potent DGAT1 Inhibitors in the Benzimidazole Class with a Pyridyl-oxy-cyclohexanecarboxylic Acid Moiety. ACS Medicinal Chemistry Letters 4:8, pages 773-778.
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Jinqi Liu, Judith N. Gorski, Stephen J. Gold, Dunlu Chen, Shirley Chen, Gail Forrest, Yoshiki Itoh, Donald J. Marsh, David G. McLaren, Zhu Shen, Lisa Sonatore, Ester Carballo-Jane, Stephanie Craw, Xiaoming Guan, Bindhu Karanam, Junichi Sakaki, Daphne Szeto, Xinchun Tong, Jianying Xiao, Ryo Yoshimoto, Hong Yu, Thomas P. Roddy, James Balkovec & Shirly Pinto. (2013) Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight and modulates gut peptide release-Potential insight into mechanism of action. Obesity 21:7, pages 1406-1415.
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Gudrun Schober, Myrtha Arnold, Susan Birtles, Linda K. Buckett, Gustavo Pacheco-López, Andrew V. Turnbull, Wolfgang Langhans & Abdelhak Mansouri. (2013) Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats. Journal of Lipid Research 54:5, pages 1369-1384.
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Pauline C. Ting, Joe F. Lee, Nicolas Zorn, Hyunjin M. Kim, Robert G. Aslanian, Mingxiang Lin, Michelle Smith, Scott S. Walker, John Cook, Margaret Van Heek & Jean Lachowicz. (2013) Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors. Bioorganic & Medicinal Chemistry Letters 23:4, pages 985-988.
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Hyae Gyeong Cheon. (2013) Latest research and development trends in non-insulin anti-diabetics. Archives of Pharmacal Research 36:2, pages 145-153.
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Kyeong Lee, Minkyoung Kim, Boah Lee, Jail Goo, Jiyoung Kim, Ravi Naik, Jee Hee Seo, Mun Ock Kim, Youngjoo Byun, Gyu-Yong Song, Hyun Sun Lee & Yongseok Choi. (2013) Discovery of indolyl acrylamide derivatives as human diacylglycerol acyltransferase-2 selective inhibitors. Org. Biomol. Chem. 11:5, pages 849-858.
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William McCoull, Matthew S. Addie, Alan M. Birch, Susan Birtles, Linda K. Buckett, Roger J. Butlin, Suzanne S. Bowker, Scott Boyd, Stephen Chapman, Robert D.M. Davies, Craig S. Donald, Clive P. Green, Chloe Jenner, Paul D. Kemmitt, Andrew G. Leach, Graeme C. Moody, Pablo Morentin Gutierrez, Nicholas J. Newcombe, Thorsten Nowak, Martin J. Packer, Alleyn T. Plowright, John Revill, Paul Schofield, Chris Sheldon, Steve Stokes, Andrew V. Turnbull, Steven J.Y. Wang, David P. Whalley & J. Matthew Wood. (2012) Identification, optimisation and in vivo evaluation of oxadiazole DGAT-1 inhibitors for the treatment of obesity and diabetes. Bioorganic & Medicinal Chemistry Letters 22:12, pages 3873-3878.
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Rosalind A. Coleman & Douglas G. Mashek. (2011) Mammalian Triacylglycerol Metabolism: Synthesis, Lipolysis, and Signaling. Chemical Reviews 111:10, pages 6359-6386.
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Robert L. Dow, Jian-Cheng Li, Michael P. Pence, E. Michael Gibbs, Jennifer L. LaPerle, John Litchfield, David W. Piotrowski, Michael J. Munchhof, Tara B. Manion, William J. Zavadoski, Gregory S. Walker, R. Kirk McPherson, Susan Tapley, Eliot Sugarman, Angel Guzman-Perez & Paul DaSilva-Jardine. (2011) Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1. ACS Medicinal Chemistry Letters 2:5, pages 407-412.
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Yimin Qian, Stanley J. Wertheimer, Mushtaq Ahmad, Adrian Wai-Hing Cheung, Fariborz Firooznia, Matthew M. Hamilton, Stuart Hayden, Shiming Li, Nicholas Marcopulos, Lee McDermott, Jenny Tan, Weiya Yun, Liang Guo, Anjula Pamidimukkala, Yingsi Chen, Kuo-Sen Huang, Gwendolyn B. Ramsey, Toni Whittard, Karin Conde-Knape, Rebecca Taub, Cristina M. Rondinone, Jefferson Tilley & David Bolin. (2011) Discovery of Orally Active Carboxylic Acid Derivatives of 2-Phenyl-5-trifluoromethyloxazole-4-carboxamide as Potent Diacylglycerol Acyltransferase-1 Inhibitors for the Potential Treatment of Obesity and Diabetes. Journal of Medicinal Chemistry 54:7, pages 2433-2446.
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