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

Mapping the Melatonin Receptor. 6. Melatonin Agonists and Antagonists Derived from 6H-Isoindolo[2,1-a]indoles, 5,6-Dihydroindolo[2,1-a]isoquinolines, and 6,7-Dihydro-5H-benzo[c]azepino[2,1-a]indoles

View Author Information
Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, U.K.
Department of Pharmacy, Division of Pharmaceutical Chemistry, University of Athens, Panepistimiopolis-Zografou, Athens 157 71, Greece
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vas. Constantinou Ave., Athens 116 35, Greece
Physiology Division, School of Biomedical Sciences, New Hunts House, King's College London, Guy's Campus, London SE1 1UL, U.K.
Cite this: J. Med. Chem. 2000, 43, 6, 1050–1061
Publication Date (Web):March 23, 2000
Copyright © 2000 American Chemical Society

    Article Views





    Other access options
    Supporting Info (1)»


    Abstract Image

    6H-Isoindolo[2,1-a]indoles (5, 7, 10, 13), 5,6-dihydroindolo[2,1-a]isoquinolines (20, 21), and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles (23, 25, 27, 30) have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human mt1 and MT2 receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores. The 2-methoxyisoindolo[2,1-a]indoles (7ad) showed much higher binding affinities than the parent isoindoles (5ae), and whereas 7ac were agonists in the functional assay, 7d and 5ae were antagonists. The 2-ethoxyisoindolo[2,1-a]indoles (10ad) showed reduced binding affinities compared to their methoxy analogues, while the 5-chloro derivative 13 showed a considerable reduction in binding affinity and potency compared to 7a. The 10-methoxy-5,6-dihydroindolo[2,1-a]isoquinolines (21ac) had higher binding affinities than the corresponding parent indoloisoquinolines (20ac) in the human receptor subtypes, and the parent compounds were antagonists whereas the 10-methoxy derivatives were agonists in the functional assay. The N-cyclobutanecarbonyl derivatives of both the parent (20d) and 10-methoxyl (21d) series had similar binding affinities and were both antagonists with similar potencies. The 11-methoxy-6,7-5H-benzo[c]azepino[2,1-a]indoles (25ad) had higher binding affinities than the corresponding parent compounds (23ad) at the MT2 receptor but similar affinities at the mt1 site; all of the compounds were antagonists in the functional assay. Changing 11-methoxy for 11-ethoxy decreased the binding affinity slightly, and this was more evident at the MT2 receptor. All of the derivatives investigated had either the same or a greater affinity for the human MT2 receptor compared to the mt1 receptor (range 1:1−1:132). This suggests that the mt1 and MT2 receptor pockets differ in their ability to accommodate alkyl groups in the indole nitrogen region of the melatonin molecule. Two compounds (7c and 25c) were tested in functional assays on recombinant mt1 and MT2 melatonin receptors. Compound 7c is a potent agonist with some selectivity (44-fold) for the MT2 receptor, while 25c is an MT2-preferring antagonist. Increasing the carbon chain length between N-1 of indole and the 2-phenyl group from n = 1 through n = 3 leads to a fairly regular decrease in the binding affinity, but, remarkably, when n = 3, it converts the methoxy compounds from melatonin agonists to antagonists. The Xenopus melatonin receptor thus cannot accommodate an N-n-alkyl chain attached to a 2-phenyl substituent with n > 2 in the required orientation to induce or stabilize the active receptor conformation.

    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.


    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.


     To whom correspondence may be addressed. Tel:  44-2076794620. Fax:  44-2076797463. E-mail:  [email protected].

    Supporting Information Available

    Jump To

    Full physical data, in the same format as for the representative examples, are provided for all analogues. This material is available free of charge via the Internet at

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system:

    Cited By

    This article is cited by 130 publications.

    1. Shengjun Liu, Congcong Zhao, Mei Pan, Hailin Liao, Yun Liu, Jinpeng Zhang, Liangce Rong. Copper(I)-Catalyzed Radical Carbamylation/Cyclization of 2-Aryl-N-methacryloylindoles with Substituted Formamides to Assemble Amidated Indolo[2,1-a]isoquinolin-6(5H)-ones. The Journal of Organic Chemistry 2023, 88 (23) , 16352-16364.
    2. Wei-Jung Chiu, Ting-Yen Chu, Indrajeet J. Barve, Chung-Ming Sun. Pd(II)-Catalyzed [5 + 2] Cyclization of N-Triflyl Aryl Indoles and α,γ-Substituted Allenoates: A Route to Indole-Fused Benzodiazepines. Organic Letters 2023, 25 (34) , 6246-6250.
    3. Yuemei Li, Shuwei Zhang, Han Ding, Zheng Sun, Qiyuan Ma, Yu Yuan, Xiaodong Jia. Halogen Bond (XB) Promoted α-Tribromomethylation of N-Aryltetrahydroisoquinolines and Further Cyclization to 5,6-Dihydroindolo[2,1-a]isoquinolines. The Journal of Organic Chemistry 2023, 88 (15) , 11310-11321.
    4. Ying-Jie Ma, Zi-Hang Yuan, Pin Gao, Xin-Hua Duan, Hong Xin, Le Liu, Li-Na Guo. Divergent Construction of Azaheterocycles via Alkoxyl Radical-Triggered C–C Bond Cleavage/Cyclization of N-Functionalized Acrylamides. The Journal of Organic Chemistry 2023, 88 (14) , 9927-9940.
    5. Siqi Wang, Shuwei Li, Liangcai Liu, Jun Ying, Xiao-Feng Wu. Palladium-Catalyzed Carbonylative Synthesis of Amide-Containing Indolo[2,1-a]isoquinolines from Alkene-Tethered Indoles and Nitroarenes. Organic Letters 2023, 25 (5) , 821-825.
    6. Akshay Subhash Narode, Rai-Shung Liu. Gold-Catalyzed Bicyclic Annulations of N-(o-Alkynylphenyl)imines with α-Diazo Esters to Form 5,6-Dihydroindolo[2,1-a]isoquinolines. Organic Letters 2022, 24 (11) , 2165-2169.
    7. Lin Li, Xin-Lian Liu, Zhuang Qi, Ai-Hua Yang, Ai-Jun Ma, Jin-Bao Peng. Palladium-Catalyzed Carbonylative Sonogashira/Annulation Reaction: Synthesis of Indolo[1,2-b]isoquinolines. Organic Letters 2022, 24 (5) , 1201-1206.
    8. Weiyou Zhou, Anwei Wang, Zhenji Kong, Xiaoting Tian, Zhenzhen Xia, Zhihui Zhang, Mingyang He, Qun Chen, Shixin Sun. Construction of Indoline-Fused Tetrahydroisoquinolines through a Domino Coupling Reaction Catalyzed by CuCoFe Layered Double Hydroxide. Organic Letters 2021, 23 (16) , 6321-6325.
    9. Henning J. Loui, Arun Suneja, Christoph Schneider. Cooperative Rh/Chiral Phosphoric Acid Catalysis toward the Highly Stereoselective (3 + 3)-Cycloannulation of Carbonyl Ylides and Indolyl-2-methides. Organic Letters 2021, 23 (7) , 2578-2583.
    10. Somadrita Borthakur, Bipul Sarma, Sanjib Gogoi. Ruthenium(II)-Catalyzed Oxidative Double C–H Activation and Annulation Reaction: Synthesis of Indolo[2,1-a]isoquinolines. Organic Letters 2019, 21 (19) , 7878-7882.
    11. Xiumei Yang, Haiyan Lu, Xiaoming Zhu, Liwei Zhou, Guobo Deng, Yuan Yang, Yun Liang. Palladium-Catalyzed Cascade Cyclization of Alkene-Tethered Aryl Halides with o-Bromobenzoic Acids: Access to Diverse Fused Indolo[2,1-a]isoquinolines. Organic Letters 2019, 21 (18) , 7284-7288.
    12. Xiang-Huan Shan, Bo Yang, Hong-Xing Zheng, Jian-Ping Qu, Yan-Biao Kang. Phenanthroline-tBuOK Promoted Intramolecular C–H Arylation of Indoles with ArI under Transition-Metal-Free Conditions. Organic Letters 2018, 20 (24) , 7898-7901.
    13. Jeffrey Bien, Akin Davulcu, Albert J. DelMonte, Kenneth J. Fraunhoffer, Zhinong Gao, Chao Hang, Yi Hsiao, Wenhao Hu, Kishta Katipally, Adam Littke, Aghogho Pedro, Yuping Qiu, Maria Sandoval, Richard Schild, Michelle Soltani, Anthony Tedesco, Dale Vanyo, Purushotham Vemishetti, Robert E. Waltermire. The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor. Organic Process Research & Development 2018, 22 (10) , 1393-1408.
    14. 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.
    15. Daniele Pala, Thijs Beuming, Woody Sherman, Alessio Lodola, Silvia Rivara, and Marco Mor . Structure-Based Virtual Screening of MT2 Melatonin Receptor: Influence of Template Choice and Structural Refinement. Journal of Chemical Information and Modeling 2013, 53 (4) , 821-835.
    16. Annalida Bedini, Simone Lucarini, Gilberto Spadoni, Giorgio Tarzia, Francesco Scaglione, Silvana Dugnani, Marilou Pannacci, Valeria Lucini, Caterina Carmi, Daniele Pala, Silvia Rivara, and Marco Mor . Toward the Definition of Stereochemical Requirements for MT2-Selective Antagonists and Partial Agonists by Studying 4-Phenyl-2-propionamidotetralin Derivatives. Journal of Medicinal Chemistry 2011, 54 (24) , 8362-8372.
    17. Didier G. Pintori and Michael F. Greaney . Intramolecular Oxidative C−H Coupling for Medium-Ring Synthesis. Journal of the American Chemical Society 2011, 133 (5) , 1209-1211.
    18. Ding Du, Linxia Li and Zhongwen Wang. N-Heterocyclic Carbene-Catalyzed Domino Ring-Opening/Redox Amidation/Cyclization Reactions of Formylcyclopropane 1,1-Diesters: Direct Construction of a 6−5−6 Tricyclic Hydropyrido[1,2-a]indole Skeleton. The Journal of Organic Chemistry 2009, 74 (11) , 4379-4382.
    19. Brooks E. Maki and Karl A. Scheidt. Single-Flask Synthesis of N-Acylated Indoles by Catalytic Dehydrogenative Coupling with Primary Alcohols. Organic Letters 2009, 11 (7) , 1651-1654.
    20. Darius P. Zlotos, Mohamed I. Attia, Justin Julius, Shalini Sethi and Paula A. Witt-Enderby. 2-[(2,3-Dihydro-1H-indol-1-yl)methyl]melatonin Analogues: A Novel Class of MT2-Selective Melatonin Receptor Antagonists. Journal of Medicinal Chemistry 2009, 52 (3) , 826-833.
    21. Silvia Rivara, Alessio Lodola, Marco Mor, Annalida Bedini, Gilberto Spadoni, Valeria Lucini, Marilou Pannacci, Franco Fraschini, Francesco Scaglione, Rafael Ochoa Sanchez, Gabriella Gobbi and Giorgio Tarzia . N-(Substituted-anilinoethyl)amides: Design, Synthesis, and Pharmacological Characterization of a New Class of Melatonin Receptor Ligands. Journal of Medicinal Chemistry 2007, 50 (26) , 6618-6626.
    22. Andrew Tsotinis, Pandelis A. Afroudakis, Kathryn Davidson, Anjali Prashar and David Sugden. Design, Synthesis, and Melatoninergic Activity of New Azido- and Isothiocyanato-Substituted Indoles. Journal of Medicinal Chemistry 2007, 50 (25) , 6436-6440.
    23. Laura J. Marshall,, Mark D. Roydhouse,, Alexandra M. Z. Slawin, and, John C. Walton. Effect of Chain Length on Radical to Carbanion Cyclo-Coupling of Bromoaryl Alkyl-Linked Oxazolines:  1,3-Areneotropic Migration of Oxazolines. The Journal of Organic Chemistry 2007, 72 (3) , 898-911.
    24. Dino Alberico,, Mark E. Scott, and, Mark Lautens. Aryl−Aryl Bond Formation by Transition-Metal-Catalyzed Direct Arylation. Chemical Reviews 2007, 107 (1) , 174-238.
    25. Andrew Tsotinis,, Margarita Vlachou,, Demetris P. Papahatjis,, Theodora Calogeropoulou,, Spyros P. Nikas,, Peter J. Garratt,, Vincent Piccio,, Stefan Vonhoff,, Kathryn Davidson,, Muy-Teck Teh, and, David Sugden. Mapping the Melatonin Receptor. 7. Subtype Selective Ligands Based on β-Substituted N-Acyl-5-methoxytryptamines and β-Substituted N-Acyl-5-methoxy-1-methyltryptamines. Journal of Medicinal Chemistry 2006, 49 (12) , 3509-3519.
    26. Cyril Bressy,, Dino Alberico, and, Mark Lautens. A Route to Annulated Indoles via a Palladium-Catalyzed Tandem Alkylation/Direct Arylation Reaction. Journal of the American Chemical Society 2005, 127 (38) , 13148-13149.
    27. Silvia Rivara,, Simone Lorenzi,, Marco Mor,, Pier Vincenzo Plazzi,, Gilberto Spadoni,, Annalida Bedini, and, Giorgio Tarzia. Analysis of Structure−Activity Relationships for MT2 Selective Antagonists by Melatonin MT1 and MT2 Receptor Models. Journal of Medicinal Chemistry 2005, 48 (12) , 4049-4060.
    28. Valeria Lucini,, Marilou Pannacci,, Francesco Scaglione,, Franco Fraschini,, Sivia Rivara,, Marco Mor,, Fabrizio Bordi,, Pier Vincenzo Plazzi,, Gilberto Spadoni,, Annalida Bedini,, Giovanni Piersanti,, Giuseppe Diamantini, and, Giorgio Tarzia. Tricyclic Alkylamides as Melatonin Receptor Ligands with Antagonist or Inverse Agonist Activity. Journal of Medicinal Chemistry 2004, 47 (17) , 4202-4212.
    29. 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.
    30. Carole Descamps-François,, Saïd Yous,, Philippe Chavatte,, Valérie Audinot,, Anne Bonnaud,, Jean A. Boutin,, Philippe Delagrange,, Caroline Bennejean,, Pierre Renard, and, Daniel Lesieur. Design and Synthesis of Naphthalenic Dimers as Selective MT1 Melatoninergic Ligands. Journal of Medicinal Chemistry 2003, 46 (7) , 1127-1129.
    31. Tom Y. H. Wu and, Peter G. Schultz. A Versatile Linkage Strategy for Solid-Phase Synthesis of N,N-Dimethyltryptamines and β-Carbolines. Organic Letters 2002, 4 (23) , 4033-4036.
    32. Valérie Wallez,, Sophie Durieux-Poissonnier,, Philippe Chavatte,, Jean A. Boutin,, Valérie Audinot,, Jean-Paul Nicolas,, Caroline Bennejean,, Philippe Delagrange,, Pierre Renard, and, Daniel Lesieur. Synthesis and Structure−Affinity−Activity Relationships of Novel Benzofuran Derivatives as MT2 Melatonin Receptor Selective Ligands. Journal of Medicinal Chemistry 2002, 45 (13) , 2788-2800.
    33. Gilberto Spadoni,, Cesarino Balsamini,, Giuseppe Diamantini,, Andrea Tontini, and, Giorgio Tarzia, , Marco Mor,, Silvia Rivara, and, Pier Vincenzo Plazzi, , Romolo Nonno,, Valeria Lucini,, Marilou Pannacci,, Franco Fraschini, and, Bojidar Michaylov Stankov. 2-N-Acylaminoalkylindoles:  Design and Quantitative Structure−Activity Relationship Studies Leading to MT2-Selective Melatonin Antagonists. Journal of Medicinal Chemistry 2001, 44 (18) , 2900-2912.
    34. Wenjun Lu,, Chengguo Jia,, Tsugio Kitamura, and, Yuzo Fujiwara. Pd-Catalyzed Selective Addition of Heteroaromatic C−H Bonds to C−C Triple Bonds under Mild Conditions. Organic Letters 2000, 2 (19) , 2927-2930.
    35. Yunfei Tian, Dongyu Guo, Luping Zheng, Shaolu Yang, Ningning Zhang, Weijun Fu, Zejiang Li. Electrochemical Radical Tandem Difluoroethylation/Cyclization of Unsaturated Amides to Access MeCF2-Featured Indolo/Benzoimidazo [2,1-a]Isoquinolin-6(5H)-ones. Molecules 2024, 29 (5) , 973.
    36. Yueqin Feng, Xiaowen Jiang, Wenwu Liu, Hongyuan Lu. The location, physiology, pathology of hippocampus Melatonin MT2 receptor and MT2-selective modulators. European Journal of Medicinal Chemistry 2023, 262 , 115888.
    37. Zuguang Yang, Pinyi Li, Zhengkai Chen, Xiao‐Feng Wu. Rh(III)‐Catalyzed Cascade Cyclization of 2‐Aryl‐3 H ‐indoles and CF 3 ‐Imidoyl Sulfoxonium Ylides Toward Trifluoroacetimidoyl‐Substituted 11 H ‐Isoindolo[2,1‐a]indoles. Advanced Synthesis & Catalysis 2023, 43
    38. Dong-Liang Zhang, Zhi-Qiang Zhu, Zong-Bo Xie, Xiao-Ping Zhang, Zhang-Gao Le. Organophotocatalytic cascade cyclization reactions for the synthesis of cyanoalkyl indole[2,1- a ]isoquinolinones. New Journal of Chemistry 2023, 47 (39) , 18354-18358.
    39. Yucai Tang, Yiting Yang, Qian Zhou, Jinglin Duan, Biyu Yang, Changyuan Du, Yupeng He. Metal- and additive-free radical-triggered nitration/cyclization to construct indolo[2,1- α ]isoquinoline and benzimidazo[2,1- a ]isoquinolin-6(5 H )-one derivatives using t -BuONO as nitro reagents. Organic & Biomolecular Chemistry 2023, 21 (25) , 5254-5264.
    40. Sonam Sharma, Gurdeep Singh, Rekha, Munnu Kumar, Ramasamy Vijaya Anand. Acid-catalysed intramolecular Friedel–Crafts annulation of hetero-atom-functionalized para -quinone methides: access to O-, S- and N-based heterocycles. Organic & Biomolecular Chemistry 2023, 21 (24) , 5072-5078.
    41. Siqi Wang, Jian-Shu Wang, Jun Ying, Xiao-Feng Wu. Palladium-catalyzed carbonylative cyclization of alkene-tethered indoles with phenols or arylboronic acids: Construction of carbonyl-containing indolo[2,1-a]isoquinoline derivatives. Chinese Chemical Letters 2023, 34 (5) , 107873.
    42. Sumi Changmai, Tribeni Gogoi, Jyotshna Phukon, Bipul Das, Sanjib Gogoi. Ru( ii )-catalyzed oxidative coupling of sulfoxonium ylides with amines: efficient synthesis of α-ketoamides and indolo[2,1- a ]isoquinolines. Organic & Biomolecular Chemistry 2023, 21 (15) , 3235-3244.
    43. Navjeet Kaur. Synthesis of azocines. 2023, 1-39.
    44. Min Li, Yucai Tang, Xingxian Xiang, Yiting Yang, Qian Zhou, Kaiming Dai, Feifei Wang. A Metal-Free TBHP-Triggered Cascade Cyclization of 2-Arylindoles with Alcohols: Synthesis of Hydroxyalkylated Indolo[2,1-a]isoquinoline Derivatives. Synlett 2022, 33 (20) , 2038-2042.
    45. Zhonghua Sun, Jie Yao, Shuliang Ji, Weiyou Zhou, Anwei Wang, Mingyang He, Xianjun Hua, Yupeng Liu. FeCl 2 /TBAC efficiently catalyzes domino coupling reactions for constructing indoline-fused tetrahydroisoquinolines. New Journal of Chemistry 2022, 46 (41) , 19643-19647.
    46. Jian-Shu Wang, Jiangjie Zhang, Siqi Wang, Jun Ying, Chuan-Ying Li, Xiao-Feng Wu. Palladium-catalyzed domino carbonylative cyclization to access functionalized heterocycles. Journal of Catalysis 2022, 414 , 313-318.
    47. Binyan Qin, Shaoxin Huang, Jian-Qiang Chen, Wei Xiao, Jie Wu. Metal-free synthesis of sulfonylated indolo[2,1- a ]isoquinolines from sulfur dioxide. Organic Chemistry Frontiers 2022, 9 (13) , 3521-3526.
    48. Mei-Ling Liu, Jing-Ling Wang, Xue-Song Li, Wen-Hui Sun, Xue-Yuan Liu. Copper-catalyzed amino radical tandem cyclization toward the synthesis of indolo-[2,1- a ]isoquinolines. Organic Chemistry Frontiers 2022, 9 (9) , 2438-2443.
    49. Jie Zhang, Zixian Yang, Jin-Tao Yu, Changduo Pan. Three-component synthesis of arylsulfonyl-substituted indolo[2,1- a ]isoquinolinones and benzimidazo-[2,1- a ]isoquinolin-6(5 H )-ones by SO 2 insertion and radical cascade cyclization. Organic & Biomolecular Chemistry 2022, 20 (15) , 3067-3071.
    50. Gian Marco Elisi, Laura Scalvini, Alessio Lodola, Annalida Bedini, Gilberto Spadoni, Silvia Rivara. In silico drug discovery of melatonin receptor ligands with therapeutic potential. Expert Opinion on Drug Discovery 2022, 17 (4) , 343-354.
    51. Na Ma, Lin Guo, Zheng-Jia Shen, Dan Qi, Chao Yang, Wujiong Xia. Cascade cyclization for the synthesis of indolo[2,1-α]isoquinoline derivatives via visible-light-induced halogen-atom-transfer (XAT) and hydrogen-atom-transfer (HAT). Organic & Biomolecular Chemistry 2022, 20 (8) , 1731-1737.
    52. Shengxian Zhai, Shuxian Qiu, Shuai Yang, Bingyan Hua, Yongsheng Niu, Chuchu Han, Youzhu Yu, Yuchao Li, Hongbin Zhai. Synthesis of arylsulfonyl-substituted indolo[2,1-a]isoquinolin-6(5H)-one derivatives via a TBAI-catalyzed radical cascade cyclization. Chinese Chemical Letters 2022, 33 (1) , 276-279.
    53. Qiaoyan Xing, Chunlan Zhou, Shuxin Jiang, Shanping Chen, Guo-Jun Deng. Acid-catalyzed three-component addition of carbonyl compounds with 1,2,3-triazoles and indoles. Organic & Biomolecular Chemistry 2021, 19 (36) , 7838-7842.
    54. Manar M. Arafeh, Ebrahim Saeedian Moghadam, Sirin A. I. Adham, Raphael Stoll, Raid J. Abdel-Jalil. Synthesis and Cytotoxic Activity Study of Novel 2-(Aryldiazenyl)-3-methyl-1H-benzo[g]indole Derivatives. Molecules 2021, 26 (14) , 4240.
    55. Rajeev V. Hegde, Tiow-Gan Ong, Ram Ambre, Arvind H. Jadhav, Siddappa A. Patil, Ramesh B. Dateer. Regioselective Direct C2 Arylation of Indole, Benzothiophene and Benzofuran: Utilization of Reusable Pd NPs and NHC-Pd@MNPs Catalyst for C–H Activation Reaction. Catalysis Letters 2021, 151 (5) , 1397-1405.
    56. Jianhua Liao, Xiao Yang, Lu Ouyang, Yinlong Lai, Jiuzhong Huang, Renshi Luo. Recent advances in cascade radical cyclization of radical acceptors for the synthesis of carbo- and heterocycles. Organic Chemistry Frontiers 2021, 8 (6) , 1345-1363.
    57. Haiyan Lu, Xiumei Yang, Liwei Zhou, Wenguang Li, Guobo Deng, Yuan Yang, Yun Liang. Palladium-catalyzed domino Heck-disilylation and -borylation of alkene-tethered 2-(2-halophenyl)-1 H -indoles: access to diverse disilylated and borylated indolo[2,1- a ]isoquinolines. Organic Chemistry Frontiers 2020, 7 (15) , 2016-2021.
    58. Shuai-Shuai Jiang, Yu-Ting Xiao, Yan-Chen Wu, Shu-Zheng Luo, Ren-Jie Song, Jin-Heng Li. Manganese( iii )-promoted tandem phosphinoylation/cyclization of 2-arylindoles/2-arylbenzimidazoles with disubstituted phosphine oxides. Organic & Biomolecular Chemistry 2020, 18 (25) , 4843-4847.
    59. Andrew Tsotinis, Ioannis P. Papanastasiou. Synthetic Melatonin Receptor Agonists and Antagonists. 2020
    60. Nilesh Kahar, Pankaj Jadhav, R. V. Ramana Reddy, Sudam Dawande. A rhodium( ii ) catalysed domino synthesis of azepino fused diindoles from isatin tethered N -sulfonyl-1,2,3-triazoles and indoles. Chemical Communications 2020, 56 (8) , 1207-1210.
    61. Su-Yan Wang, Xin-Chi Shi, Pedro Laborda. Indole-based melatonin analogues: Synthetic approaches and biological activity. European Journal of Medicinal Chemistry 2020, 185 , 111847.
    62. Jiawen Yang, Wenwen Gu, Yu Li. Biological enrichment prediction of polychlorinated biphenyls and novel molecular design based on 3D-QSAR/HQSAR associated with molecule docking. Bioscience Reports 2019, 39 (5)
    63. Yun-Long Wei, Jian-Qiang Chen, Bo Sun, Peng-Fei Xu. Synthesis of indolo[2,1- a ]isoquinoline derivatives via visible-light-induced radical cascade cyclization reactions. Chemical Communications 2019, 55 (42) , 5922-5925.
    64. Andrew Tsotinis, Rodanthi Kompogennitaki, Ioannis Papanastasiou, Peter J. Garratt, Alina Bocianowska, David Sugden. Fluorine substituted methoxyphenylalkyl amides as potent melatonin receptor agonists. MedChemComm 2019, 10 (3) , 460-464.
    65. Célia Gautier, Sophie-Penelope Guenin, Isabelle Riest-Fery, Tahlia Jade Perry, Céline Legros, Olivier Nosjean, Valerie Simonneaux, Frank Grützner, Jean A. Boutin, . Characterization of the Mel1c melatoninergic receptor in platypus (Ornithorhynchus anatinus). PLOS ONE 2018, 13 (3) , e0191904.
    66. Zi-Qi Zhu, Lei Yin, Yang Wang, Yang Shen, Can Li, Guang-Jian Mei, Feng Shi. Diastereo- and enantioselective construction of biologically important pyrrolo[1,2-a]indole scaffolds via catalytic asymmetric [3 + 2] cyclodimerizations of 3-alkyl-2-vinylindoles. Organic Chemistry Frontiers 2017, 4 (1) , 57-68.
    67. Venkataramanujam Srinivasan, Rahimah Zakaria, Domenico de Berardis, Francisco López-Muñoz, Mohd Jamil Yaacob, Zahiruddin Othman, Amnon Brzezinski. Melatonergic Drug Ramelteon in Neurotherapeutics. 2016, 203-217.
    68. Laure Théveau, Cédric Schneider, Olivier Querolle, Lieven Meerpoel, Vincent Levacher, Christophe Hoarau. Synthesis and orthogonal functionalization of oxazolo[5′,4′:4,5]pyrano[2,3-b]pyridine by intra- and intermolecular Pd-catalyzed direct C–H bond heteroarylation. Organic & Biomolecular Chemistry 2016, 14 (13) , 3459-3468.
    69. G. Viault, S. Poupart, S. Mourlevat, C. Lagaraine, S. Devavry, F. Lefoulon, V. Bozon, L. Dufourny, P. Delagrange, G. Guillaumet, F. Suzenet. Design, synthesis and biological evaluation of fluorescent ligands for MT 1 and/or MT 2 melatonin receptors. RSC Advances 2016, 6 (67) , 62508-62521.
    70. Jun Li, Yang Tang, Hui-Juan Jin, Yi-Di Cui, Li-Juan Zhang, Tao Jiang. An efficient synthesis method targeted to marine alkaloids marinacarbolines A–D and their antitumor activities. Journal of Asian Natural Products Research 2015, 17 (3) , 299-305.
    71. Navjeet Kaur. Palladium Catalysts: Synthesis of Five-Membered N -Heterocycles Fused with Other Heterocycles. Catalysis Reviews 2015, 57 (1) , 1-78.
    72. Almudena Crooke, Ana Guzman-Aranguez, Aranzazu Mediero, Pilar Alarma-Estrany, Gonzalo Carracedo, Teresa Pelaez, Assumpta Peral, Jesús Pintor. Effect of Melatonin and Analogues on Corneal Wound Healing: Involvement of Mt 2 Melatonin Receptor. Current Eye Research 2015, 40 (1) , 56-65.
    73. Raid J. Abdel-Jalil, Manar M. Arafeh, Musa S. Shongwe, Cäcilia Maichle-Mößmer, Gabriele Kociok-Köhn, Wolfgang Voelter. 1-(Naphthylamino)-1-( p -chlorophenylhydrazono)-2-propanone and 2-( p -tolyldiazenyl)-[1 H ]-3-methylbenzo[ g ]indole: Crystallographic and spectroscopic elucidation of the cyclisation of an arylamidrazone. Journal of Molecular Structure 2015, 1079 , 307-314.
    74. Yueqing Hu, King H. Chan, Xixin He, Maurice K. C. Ho, Yung H. Wong, . Synthesis and Functional Characterization of Substituted Isoquinolinones as MT2-Selective Melatoninergic Ligands. PLoS ONE 2014, 9 (12) , e113638.
    75. N. V. Kostiuk, M. B. Belyakova, D. V. Leshchenko, V. V. Zhigulina, M. V. Miniaev. Synthetic Melatoninergic Ligands: Achievements and Prospects. ISRN Biochemistry 2014, 2014 , 1-11.
    76. King Chan, Yung Wong. A Molecular and Chemical Perspective in Defining Melatonin Receptor Subtype Selectivity. International Journal of Molecular Sciences 2013, 14 (9) , 18385-18406.
    77. Jemin R. Avalani, Devji S. Patel, Dipak K. Raval. Saccharomyces cerevisiae catalyzed one pot synthesis of isoindolo[2,1-a]quinazoline performed under ultrasonication. Journal of Molecular Catalysis B: Enzymatic 2013, 90 , 70-75.
    78. Ruth Bustamante-García, Elia B. Naranjo-Rodríguez, Alfonso S. Lira-Rocha, Alejandro Ortiz-Osornio, Ofir Picazo. Behavioural actions of two new 1-N substituted analogues of melatonin. Behavioural Brain Research 2013, 236 , 148-156.
    79. Piyush Kumar Agarwal, Meena Devi Dathi, Mohammad Saifuddin, Bijoy Kundu. Engineering of indole-based tethered biheterocyclic alkaloid meridianin into β-carboline-derived tetracyclic polyheterocycles via amino functionalization/6- endo cationic π-cyclization. Beilstein Journal of Organic Chemistry 2012, 8 , 1901-1908.
    80. Saïd El Kazzouli, Amaury Griffon du Bellay, Sabine Berteina-Raboin, Philippe Delagrange, Daniel-Henry Caignard, Gérald Guillaumet. Design and synthesis of 2-phenylimidazo[1,2-a]pyridines as a novel class of melatonin receptor ligands. European Journal of Medicinal Chemistry 2011, 46 (9) , 4252-4257.
    81. 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.
    82. Jiangtao Zhu, Haibo Xie, Zixian Chen, Shan Li, Yongming Wu. Synthesis of 6-trifluoromethylindolo[1,2-c]quinazolines and related heterocycles using N-(2-iodophenyl)trifluoroacetimidoyl chlorides as starting material via C–H bond functionalization. Chem. Commun. 2011, 47 (5) , 1512-1514.
    83. David Heckman, Mohamed I. Attia, Mira A. M. Behnam, Amal M. Y. Mohsen, Christian Markl, Justin Julius, Shalini Sethi, Paula A. Witt-Enderby, Darius P. Zlotos. 2-[(1,3-Dihydro-2H-isoindol-2-yl)methyl]melatonin – a novel MT2-selective melatonin receptor antagonist. MedChemComm 2011, 2 (10) , 991.
    84. Min Ding, Feng He, Michael A. Poss, Karen L. Rigat, Ying-Kai Wang, Susan B. Roberts, Dike Qiu, Robert A. Fridell, Min Gao, Robert G. Gentles. The synthesis of novel heteroaryl-fused 7,8,9,10-tetrahydro-6H-azepino[1,2-a]indoles, 4-oxo-2,3-dihydro-1H-[1,4]diazepino[1,7-a]indoles and 1,2,4,5-tetrahydro-[1,4]oxazepino[4,5-a]indoles. Effective inhibitors of HCV NS5B polymerase. Organic & Biomolecular Chemistry 2011, 9 (19) , 6654.
    85. 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.
    86. 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.
    87. 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.
    88. K Iakovou, A Varvaresou, A P Kourounakis, K Stead, D Sugden, A Tsotinis. Design, synthesis and biological evaluation of novel β-substituted indol-3-yl ethylamido melatoninergic analogues. Journal of Pharmacy and Pharmacology 2010, 54 (1) , 147-156.
    89. Fabio Bellina, Renzo Rossi. Recent advances in the synthesis of (hetero)aryl-substituted heteroarenes via transition metal-catalysed direct (hetero)arylation of heteroarene C–H bonds with aryl halides or pseudohalides, diaryliodonium salts, and potassium aryltrifluoroborates. Tetrahedron 2009, 65 (50) , 10269-10310.
    90. Christian Markl, Mohamed I. Attia, Justin Julius, Shalini Sethi, Paula A. Witt-Enderby, Darius P. Zlotos. Synthesis and pharmacological evaluation of 1,2,3,4-tetrahydropyrazino[1,2-a]indole and 2-[(phenylmethylamino)methyl]-1H-indole analogues as novel melatoninergic ligands. Bioorganic & Medicinal Chemistry 2009, 17 (13) , 4583-4594.
    91. Simon P. Fisher, David Sugden. Sleep-promoting action of IIK7, a selective MT2 melatonin receptor agonist in the rat. Neuroscience Letters 2009, 457 (2) , 93-96.
    92. Nekane Barbero, Raul SanMartin, Esther Domínguez. Divergent synthesis of isoindolo[2,1-a]indole and indolo[1,2-a]indole through copper-catalysed C- and N-arylations. Tetrahedron Letters 2009, 50 (18) , 2129-2131.
    93. 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.
    94. József Csontos, Péter Kálmán, Gyula Tasi, Miklós Kálmán, Richard F. Murphy, Sándor Lovas. The effect of electron correlation on the conformational space of melatonin. Journal of Computational Chemistry 2008, 29 (9) , 1466-1471.
    95. Hyun Seung Lee, Sung Hwan Kim, Saravanan Gowrisankar, Jae Nyoung Kim. Palladium-mediated synthesis of poly-fused heterocycles from Baylis–Hillman adducts. Tetrahedron 2008, 64 (30-31) , 7183-7190.
    96. Valérie Audinot, Anne Bonnaud, Line Grandcolas, Marianne Rodriguez, Nadine Nagel, Jean-Pierre Galizzi, Ales Balik, Sophie Messager, David G. Hazlerigg, Perry Barrett, Philippe Delagrange, Jean A. Boutin. Molecular cloning and pharmacological characterization of rat melatonin MT1 and MT2 receptors. Biochemical Pharmacology 2008, 75 (10) , 2007-2019.
    97. A Selen Gurkan, Erdem Buyukbingol. Novel Indole Lipoic Acid Derivatives. 2008
    98. Hyun Seung Lee, Sung Hwan Kim, Taek Hyeon Kim, Jae Nyoung Kim. Pd-Mediated synthesis of 7H-benzo[3,4]azepino[1,2-a]indole-6-carboxylic acid derivatives from indole-containing Baylis–Hillman adducts. Tetrahedron Letters 2008, 49 (11) , 1773-1776.
    99. Christophe Morice, Camille G. Wermuth. Ring Transformations. 2008, 343-362.
    100. Christophe Morice, Camille G. Wermuth. Ring Transformations. 2008, 243-266.
    Load all citations

    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.

    Your Mendeley pairing has expired. Please reconnect