2-Aryladenine Derivatives as a Potent Scaffold for Adenosine Receptor Antagonists: The 6-Morpholino Derivatives

被引:0
|
作者
Areias, Filipe [1 ,2 ,3 ]
Correia, Carla [1 ]
Rocha, Ashly [1 ]
Teixeira, Sofia [1 ]
Castro, Marian [2 ,4 ]
Brea, Jose [2 ,4 ]
Hu, Huabin [5 ]
Carlsson, Jens [5 ]
Loza, Maria I. [2 ,4 ]
Proenca, M. Fernanda [1 ]
Carvalho, M. Alice [1 ]
机构
[1] Univ Minho, Ctr Chem Univ Minho CQUM, Campus Gualtar, P-4710057 Braga, Portugal
[2] Univ Santiago De Compostela, Ctr Res Mol Med & Chron Dis CiMUS, Avda Barcelona, Santiago De Compostela 15782, Spain
[3] Yachay Tech Univ, Sch Chem Sci & Engn, Urcuqui 100119, Ecuador
[4] Inst Invest Sanitaria Santiago De Compostela IDIS, Travesia Choupana S-N, E-15706 Santiago De Compostela, Spain
[5] Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, SE-75124 Uppsala, Sweden
来源
MOLECULES | 2024年 / 29卷 / 11期
关键词
G protein-coupled receptors; adenine derivatives; adenosine receptor antagonists; 2-arylpurine derivatives; structure-activity relationship; ROLOFYLLINE; LIGANDS;
D O I
10.3390/molecules29112543
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A1, A2A, A2B, and A3 adenosine receptor subtypes. Eleven purines showed potent antagonism at A1, A3, dual A1/A2A, A1/A2B, or A1/A3 adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity relationships were made for this group of new compounds. The 9-methylpurine derivatives were generally less potent but more selective, and the 9H-purine derivatives were more potent but less selective. These compounds can be an important source of new biochemical tools and/or pharmacological drugs.
引用
收藏
页数:17
相关论文
共 50 条
  • [1] 2-Aryladenine derivatives as a potent scaffold for A1, A3 and dual A1/A3 adenosine receptor antagonists: Synthesis and structure-activity relationships
    Areias, Filipe
    Correia, Carla
    Rocha, Ashly
    Brea, Jose
    Castro, Marian
    Loza, Maria, I
    Fernanda Proenca, M.
    Alice Carvalho, M.
    BIOORGANIC & MEDICINAL CHEMISTRY, 2019, 27 (16) : 3551 - 3558
  • [2] Pyrimidine Derivatives as Potent and Selective A3 Adenosine Receptor Antagonists
    Yaziji, Vicente
    Rodriguez, David
    Gutierrez-de-Teran, Hugo
    Coelho, Alberto
    Caamano, Olga
    Garcia-Mera, Xerardo
    Brea, Jose
    Isabel Loza, Maria
    Isabel Cadavid, Maria
    Sotelo, Eddy
    JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (02) : 457 - 471
  • [3] XANTHINE DERIVATIVES AS ADENOSINE RECEPTOR ANTAGONISTS
    FREDHOLM, BB
    PERSSON, CGA
    EUROPEAN JOURNAL OF PHARMACOLOGY, 1982, 81 (04) : 673 - 676
  • [4] 6-phenyl-1,4-dihydropyridine derivatives as potent and selective A(3) adenosine receptor antagonists
    Jiang, JL
    vanRhee, AM
    Melman, N
    Ji, XD
    Jacobson, KA
    JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (23) : 4667 - 4675
  • [5] Biaryl and heteroaryl derivatives of SCH 58261 as potent and selective adenosine A2A receptor antagonists
    Shah, U
    Boyle, CD
    Chackalamannil, S
    Neustadt, B
    Foster, C
    Arik, L
    Zhai, Y
    Lachowicz, JE
    Ng, K
    Shiyong, W
    Monopoli, A
    Ongini, E
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2005, 230 : U2549 - U2550
  • [6] Biaryl and heteroaryl derivatives of SCH 58261 as potent and selective adenosine A2A receptor antagonists
    Shah, Unmesh
    Boyle, Craig D.
    Chackalamannil, Samuel
    Neustadt, Bernard R.
    Lindo, Neil
    Greenlee, William J.
    Foster, Carolyn
    Arik, Leyla
    Zhai, Ying
    Ng, Kwokei
    Wang, Shiyong
    Monopoli, Angela
    Lachowicz, Jean E.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (14) : 4199 - 4203
  • [7] Novel triazolopyrazine, triazolopyrimidine, and triazolotriazine derivatives as potent and selective adenosine A2a receptor antagonists
    Kumaravel, Gnanasambandam
    Engber, Thomas
    Vu, Chi B.
    Peng, Hairuo
    Dowling, James E.
    Yao, Gang
    Vessels, Jeffery T.
    Scott, Daniel
    Petter, Russell C.
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 231
  • [8] Tricyclic imidazoline derivatives as potent and selective adenosine A1 receptor antagonists
    Vu, Chi B.
    Kiesman, William F.
    Conlon, Patrick R.
    Lin, Ko-Chung
    Tam, Melissa
    Petter, Russell C.
    Smits, Glenn
    Lutterodt, Frank
    Jin, Xiaowei
    JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (24) : 7132 - 7139
  • [9] Derivatives of 4-amino-6-hydroxy-2-mercaptopyrimidine as novel, potent, and selective A3 adenosine receptor antagonists
    Cosimelli, Barbara
    Greco, Giovanni
    Ehlardo, Marina
    Novellino, Ettore
    Da Settimo, Federico
    Taliani, Sabrina
    La Motta, Concettina
    Bellandi, Marusca
    Tuccinardi, Tiziano
    Martinelli, Adriano
    Ciampi, Osele
    Trincavelli, Maria Letizia
    Martini, Claudia
    JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (06) : 1764 - 1770
  • [10] Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships
    Cheong, Siew Lee
    Venkatesan, Gopalakrishnan
    Paira, Priyankar
    Jothibasu, Ramasamy
    Mandel, Alexander Laurence
    Federico, Stephanie
    Spalluto, Giampiero
    Pastorin, Giorgia
    INTERNATIONAL JOURNAL OF MEDICINAL CHEMISTRY, 2011, 2011