ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Synthesis of Phenalene and Acenaphthene Derivatives as New Conformationally Restricted Ligands for Melatonin Receptors

View Author Information
Faculté de Pharmacie, Université de Paris-Sud, CNRS−BIOCIS (UPRES A 8076), 5 rue J. B. Clément, 92296 Châtenay-Malabry, France, Institut de Recherche Servier, Centre de Croissy, 125 Chemin de Ronde, 78290 Croissy sur Seine, France, Institut de Recherche Internationale Servier, Place des Pléiades, 92415 Courbevoie, France, and ADIR, 1 rue Carle Hébert, 92415 Courbevoie, France
Cite this: J. Med. Chem. 2000, 43, 22, 4051–4062
Publication Date (Web):October 14, 2000
https://doi.org/10.1021/jm000922c
Copyright © 2000 American Chemical Society

    Article Views

    824

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options

    Abstract

    Abstract Image

    Conformationally restricted phenalene and acenaphthene derivatives 5 were synthesized from phenalen-1-one and acenaphthen-1-one derivatives using the Horner−Emmons reaction. The amines were prepared through the corresponding isocyanates by the Curtius reaction on the acids or by the reduction of the nitriles. Amido derivatives (R3 = Me, Et, n-Pr, c-Pr) were prepared by acylation of the amines with the appropriate anhydrides or acid chlorides or by the reductive acylation of the nitriles. The affinities of the compounds for melatonin binding sites were evaluated in vitro in binding assays using chicken brain melatonin and the human mt1 and MT2 receptors expressed in HEK-293 cells. The functionality of the compounds was determined by the potency to lighten the skin of Xenopus laevis tadpoles. Highly potent compounds were obtained. The data highlighted the role of the methoxy group located in the ortho position to the ethylamido chain as compounds with picomolar affinities such as 14c were obtained (chicken brain, hmt1, hMT2Ki values = 0.02, 0.008, 0.069 nM, respectively). Compound 14c was equipotent to the corresponding dimethoxy derivative 15c (chicken brain, hmt1, hMT2Ki values = 0.07, 0.016, 0.1 nM, respectively). On the other hand, the restricted conformation of the amido chain did not influence selectivity for the cloned hmt1 and hMT2 receptors. These compounds were also potent agonists of melanophore aggregation in X. laevis. 15a,c were several hundred fold more potent than melatonin (EC50 = 0.025, 0.004 nM, respectively). Conformational studies indicated that the minimum energy folded conformation of the ethylamido chain could constitute the putative active form in the receptor site in agreement with previous results.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    §

     CNRS−BIOCIS.

     Institut de Recherche Servier.

     ADIR.

     Institut de Recherche Internationale Servier.

    *

     To whom correspondence should be addressed. Tel:  33 1 46 83 57 36. Fax:  33 1 46 83 57 40. E-mail:  [email protected].

    Cited By

    This article is cited by 29 publications.

    1. Darius. P. Zlotos, Ralf Jockers, Erika Cecon, Silvia Rivara, and Paula A. Witt-Enderby . MT1 and MT2 Melatonin Receptors: Ligands, Models, Oligomers, and Therapeutic Potential. Journal of Medicinal Chemistry 2014, 57 (8) , 3161-3185. https://doi.org/10.1021/jm401343c
    2. Silvia Rivara,, Marco Mor,, Claudia Silva,, Valentina Zuliani,, Federica Vacondio,, Gilberto Spadoni,, Annalida Bedini,, Giorgio Tarzia,, Valeria Lucini,, Marilou Pannacci,, Franco Fraschini, and, Pier Vincenzo Plazzi. Three-Dimensional Quantitative Structure−Activity Relationship Studies on Selected MT1 and MT2 Melatonin Receptor Ligands:  Requirements for Subtype Selectivity and Intrinsic Activity Modulation. Journal of Medicinal Chemistry 2003, 46 (8) , 1429-1439. https://doi.org/10.1021/jm020982d
    3. Anna Kulesza,, Frank H. Ebetino,, Rajesh K. Mishra,, Doreen Cross-Doersen, and, Adam W. Mazur. Synthesis of 2,4,5-Trisubstituted Tetrahydropyrans as Peptidomimetic Scaffolds for Melanocortin Receptor Ligands. Organic Letters 2003, 5 (8) , 1163-1166. https://doi.org/10.1021/ol027281v
    4. Osamu Uchikawa,, Kohji Fukatsu,, Ryosuke Tokunoh,, Mitsuru Kawada,, Kiyoharu Matsumoto,, Yumi Imai,, Shuji Hinuma,, Koki Kato,, Hisao Nishikawa,, Keisuke Hirai,, Masaomi Miyamoto, and, Shigenori Ohkawa. Synthesis of a Novel Series of Tricyclic Indan Derivatives as Melatonin Receptor Agonists. Journal of Medicinal Chemistry 2002, 45 (19) , 4222-4239. https://doi.org/10.1021/jm0201159
    5. Antara Garai, Marco Villa, Marianna Marchini, Sajal Kumar Patra, Tanmoy Pain, Sruti Mondal, Paola Ceroni, Sanjib Kar. Synthesis, Structure, Photophysics, and Singlet Oxygen Sensitization by a Platinum(II) Complex of Meso ‐Tetra‐Acenaphthyl Porphyrin. European Journal of Inorganic Chemistry 2021, 2021 (39) , 4089-4095. https://doi.org/10.1002/ejic.202100667
    6. Aravind Babu Kajjam, Kasturi Singh, R. V. Varun Tej, Sivakumar Vaidyanathan. Carbazole–acenaphthene (donor–acceptor)-based luminophores for picric acid detection: a combined experimental and theoretical study. Materials Advances 2021, 2 (15) , 5236-5247. https://doi.org/10.1039/D1MA00445J
    7. Xiangfeng Lin, Yan Liu, Can Li. Allylsilane Reagent‐Controlled Divergent Asymmetric Catalytic Reactions of 2‐Naphthoquinone‐1‐methide. Chemistry – A European Journal 2020, 26 (62) , 14173-14180. https://doi.org/10.1002/chem.202002814
    8. Jean A. Boutin, Paula A. Witt‐Enderby, Christoph Sotriffer, Darius P. Zlotos. Melatonin receptor ligands: A pharmaco‐chemical perspective. Journal of Pineal Research 2020, 69 (3) https://doi.org/10.1111/jpi.12672
    9. Theodor Peez, Jan‐Niclas Luy, Klaus Harms, Ralf Tonner, Ulrich Koert. From Acenaphthenes to (+)‐Delavatine A: Visible‐Light‐Induced Ring Closure of Methyl (α‐Naphthyl) Acrylates. Chemistry – A European Journal 2018, 24 (67) , 17686-17690. https://doi.org/10.1002/chem.201804735
    10. Arun K. Ghosh, Margherita Brindisi, Anindya Sarkar. The Curtius Rearrangement: Applications in Modern Drug Discovery and Medicinal Chemistry. ChemMedChem 2018, 13 (22) , 2351-2373. https://doi.org/10.1002/cmdc.201800518
    11. Angela F. Ku, Gregory D. Cuny. Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors. MedChemComm 2018, 9 (2) , 353-356. https://doi.org/10.1039/C7MD00656J
    12. Vishruth Gowda, Brendan Foley, Jasmine Du, Megan Esteb, Coran M. H. Watanabe. Biocatalysis with the milk protein β-lactoglobulin: promoting retroaldol cleavage of α,β-unsaturated aldehydes. Organic & Biomolecular Chemistry 2018, 16 (13) , 2210-2213. https://doi.org/10.1039/C8OB00139A
    13. Mohammad K Mohammadi, Omidreza Firuzi, Mehdi Khoshneviszadeh, Nima Razzaghi-Asl, Saghi Sepehri, Ramin Miri. Novel 9-(alkylthio)-Acenaphtho[1,2-e]-1,2,4-triazine derivatives: synthesis, cytotoxic activity and molecular docking studies on B-cell lymphoma 2 (Bcl-2). DARU Journal of Pharmaceutical Sciences 2014, 22 (1) https://doi.org/10.1186/2008-2231-22-2
    14. Laurence Morellato, Marie Lefas-Le Gall, Michel Langlois, Daniel-Henri Caignard, Pierre Renard, Philippe Delagrange, Monique Mathé-Allainmat. Synthesis of new N-(arylcyclopropyl)acetamides and N-(arylvinyl)acetamides as conformationally-restricted ligands for melatonin receptors. Bioorganic & Medicinal Chemistry Letters 2013, 23 (2) , 430-434. https://doi.org/10.1016/j.bmcl.2012.11.069
    15. Christophe Mésangeau, Mikaël Fraise, Philippe Delagrange, Daniel Henri Caignard, Jean Albert Boutin, Pascal Berthelot, Saïd Yous. Preparation and pharmacological evaluation of a novel series of 2-(phenylthio)benzo[b]thiophenes as selective MT2 receptor ligands. European Journal of Medicinal Chemistry 2011, 46 (5) , 1835-1840. https://doi.org/10.1016/j.ejmech.2011.02.044
    16. Margarita L. Dubocovich, Philippe Delagrange, Diana N. Krause, David Sugden, Daniel P. Cardinali, James Olcese. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors. Pharmacological Reviews 2010, 62 (3) , 343-380. https://doi.org/10.1124/pr.110.002832
    17. Marco Mor, Silvia Rivara, Daniele Pala, Annalida Bedini, Gilberto Spadoni, Giorgio Tarzia. Recent advances in the development of melatonin MT 1 and MT 2 receptor agonists. Expert Opinion on Therapeutic Patents 2010, 20 (8) , 1059-1077. https://doi.org/10.1517/13543776.2010.496455
    18. Christophe Mésangeau, Basile Pérès, Carole Descamps-François, Philippe Chavatte, Valérie Audinot, Sophie Coumailleau, Jean A. Boutin, Philippe Delagrange, Caroline Bennejean, Pierre Renard, Daniel H. Caignard, Pascal Berthelot, Saïd Yous. Design, synthesis and pharmacological evaluation of novel naphthalenic derivatives as selective MT1 melatoninergic ligands. Bioorganic & Medicinal Chemistry 2010, 18 (10) , 3426-3436. https://doi.org/10.1016/j.bmc.2010.04.008
    19. Sophie Poissonnier-Durieux, Mohamed Ettaoussi, Basile Pérès, Jean A. Boutin, Valérie Audinot, Caroline Bennejean, Philippe Delagrange, Daniel Henri Caignard, Pierre Renard, Pascal Berthelot, Daniel Lesieur, Saïd Yous. Synthesis of 3-phenylnaphthalenic derivatives as new selective MT2 melatoninergic ligands. Bioorganic & Medicinal Chemistry 2008, 16 (18) , 8339-8348. https://doi.org/10.1016/j.bmc.2008.08.052
    20. Xing Yong Wang, Jing Nan Cui, Wei Min Ren, Feng Li, Chun Liang Lu, Xu Hong Qian. Baker's yeast mediated reduction of substituted acenaphthenequinones: Regio- and enantioselective preparation of mono-hydroxyacenaphthenones. Chinese Chemical Letters 2007, 18 (6) , 681-684. https://doi.org/10.1016/j.cclet.2007.04.022
    21. Yan Huang, Yong-Bo Zhang, Zhi-Ce Chen, Peng-Fei Xu. A concise synthesis of (R)- and (S)-α-alkyl isoserines from d- and l-malic acids. Tetrahedron: Asymmetry 2006, 17 (22) , 3152-3157. https://doi.org/10.1016/j.tetasy.2006.11.033
    22. Anton O. Chugunov, Amaury Farce, Philippe Chavatte, Roman G. Efremov. Differences in Binding Sites of Two Melatonin Receptors Help to Explain Their Selectivity to Some Melatonin Analogs: A Molecular Modeling Study. Journal of Biomolecular Structure and Dynamics 2006, 24 (2) , 91-107. https://doi.org/10.1080/07391102.2006.10507103
    23. Darius P. Zlotos. Recent Advances in Melatonin Receptor Ligands. Archiv der Pharmazie 2005, 338 (5-6) , 229-247. https://doi.org/10.1002/ardp.200400996
    24. Boyapati M. Choudary, Mannepalli L. Kantam, Kalluri V. S. Ranganath, Kottapalli K. Rao. Hydrogen Processing by Fe III ‐Exchanged Montmorillonite: A Unique Geochemical Protocol. Angewandte Chemie 2005, 117 (2) , 326-329. https://doi.org/10.1002/ange.200461070
    25. Boyapati M. Choudary, Mannepalli L. Kantam, Kalluri V. S. Ranganath, Kottapalli K. Rao. Hydrogen Processing by Fe III ‐Exchanged Montmorillonite: A Unique Geochemical Protocol. Angewandte Chemie International Edition 2005, 44 (2) , 322-325. https://doi.org/10.1002/anie.200461070
    26. Gilles Ferry, Caroline Ubeaud, Julien Mozo, Christophe Péan, Philippe Hennig, Marianne Rodriguez, Catherine Scoul, Anne Bonnaud, Olivier Nosjean, Jean‐Pierre Galizzi, Philippe Delagrange, Pierre Renard, Jean‐Paul Volland, Said Yous, Daniel Lesieur, Jean A. Boutin. New substrate analogues of human serotonin N ‐acetyltransferase produce in situ specific and potent inhibitors. European Journal of Biochemistry 2004, 271 (2) , 418-428. https://doi.org/10.1046/j.1432-1033.2003.03942.x
    27. . The Cyanophosphonates. 2003https://doi.org/10.1201/9780203503676.ch6
    28. Cécile Pégurier, Laurence Morellato, Eminn Chahed, Jean Andrieux, Jean-Paul Nicolas, Jean A Boutin, Caroline Bennejean, Philippe Delagrange, Michel Langlois, Monique Mathé-Allainmat. Synthesis of new arylalkoxy amido derivatives as melatoninergic ligands. Bioorganic & Medicinal Chemistry 2003, 11 (5) , 789-800. https://doi.org/10.1016/S0968-0896(02)00328-0
    29. W. Soudijn, I. Van Wijngaarden, A. P. Ijzerman. Enantioselectivity in Drug-Receptor Interactions. 2003, 161-182. https://doi.org/10.1007/978-3-642-55842-9_7

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect