A

SPIROCYCLIC MAGL INHIBITORS

Espacenet Family 92458339

Abstract

This invention relates to compound of formula I that are useful as inhibitors, in particular as inhibitors of monoacylglycerol lipase (MAGL). The invention also relates to uses of said compounds.

Inventors 4

  1. van der Stelt, Marcelis
  2. Mirjam C. W. Huizenga Aachen author as filed: Huizenga, Mirjam Cornelia Wellemina
  3. Antonius P. A. Janssen Aachen author as filed: Janssen, Antonius Petrus Arnoldus
  4. Richard J. B. H. N. van den Berg Aachen author as filed: van den Berg, Richard Jan Baptist Hendrikus Nouel

Inventors are linked to an Aachen author when surname and first name match exactly one author.

Applicants

Cited papers 2 in the database

Non-patent literature as cited (21)
  • - DK NOMURA ET AL.: "Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis", CELL, vol. 140, no. 1, 2010, pages 49 - 61
  • - PAGANO ET AL.: "Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis", PHARMACOL RES., vol. 5, no. 119, 2017, pages 227 - 236
  • - JIANG ET AL., NATURE COMM, 2023
  • - JIANG ET AL., J. MED. CHEM., 2024
  • - BERGE ET AL.: "Pharmaceutical Salts", JOURNAL OF PHARMACEUTICAL SCIENCE, vol. 66, 1977, pages 1 - 19, XP002675560, DOI: 10.1002/jps.2600660104
  • - "Advanced Organic Chemistry", March 2001, JOHN WILEY AND SONS
  • - E. L. ELIELS. H. WILEN: "Stereochemistry of Organic Compounds", 1994, WILEY
  • - GOODMANGILLMAN'S ET AL.: "The Pharmacological Bases of Therapeutics", 1990, MACK PUBLISHING CO.
  • - CISAR, J.S.: "Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorder", J. MED. CHEM., vol. 61, no. 20, 25 October 2018 (2018-10-25), pages 9062 - 9084, XP055675146, DOI: 10.1021/acs.jmedchem.8b00951
  • - DENG, H.LI, W: "Monoacylglycerol lipase inhibitors: Modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders", ACTA PHARMACEUTICA SINICA, vol. 8, Retrieved from the Internet <URL:https://doi.orq/10.1016/j.apsb.2019.10.006>
  • - GRANCHI, C. ET AL., EXPERT OPINION ON THERAPEUTIC PATENTS, vol. 27, no. 12, 2017, pages 1341 - 1351
  • - NOMURA D.K. ET AL.: "Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis", CELL, vol. 140, 8 January 2010 (2010-01-08), pages 49 - 61
  • - ZHU W. ET AL.: "Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF- B-mediated epithelial-mesenchymal transition", JOURNAL OF HEMATOLOGY & ONCOLOGY, no. 127, 2016, pages 9
  • - PAGANO E. ET AL.: "Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis", PHARMACOLOGICAL RESEARCH, vol. 119, 2017, pages 227 - 236, XP029980366, DOI: 10.1016/j.phrs.2017.02.002
  • - NOMURA D.K. ET AL.: "Monoacylglycerol Lipase Exerts Dual Control over Endocannabinoid and Fatty Acid Pathways to Support Prostate Cancer", CHEMISTRY AND BIOLOGY, vol. 18, no. 7, 2011, pages 846 - 856, XP028248849, DOI: 10.1016/j.chembiol.2011.05.009
  • - HU W.R ET AL.: "Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma", INT. J. CLIN. EXP. PATHOL., vol. 7, no. 7, 2014, pages 3704 - 3713
  • - STICHT M.A. ET AL.: "Inhibition of monoacylglycerol lipase attenuates vomiting in Suncus murinus and 2-arachidonoyl glycerol attenuates nausea in rats", BRITISH JOURNAL OF PHARMACOLOGY, vol. 165, no. 8, 2011, Retrieved from the Internet <URL:https://doi.org/10.1111/j.1476-5381.2011.01407.x>
  • - PROKOP, S. ET AL., NAT. COMMUN., vol. 12, 2021, pages 6505
  • - VAN ESBROECK, A. C. M. ET AL., SCIENCE, vol. 356, 1979, pages 1084 - 1087
  • - WEL T ET AL.: "A natural substrate-based fluorescence assay for inhibitor screening on diacylglycerol lipase", J LIPID RES., vol. 56, no. 4, 2015, pages 927 - 35
  • - JIANG, M. ET AL., NAT. COMMUN., vol. 14, 2023, pages 8039