Prev. Article Next Article Table of Contents

Brief Article

Structure−Activity Relationships of Truncated d- and l-4′-Thioadenosine Derivatives as Species-Independent A₃ Adenosine Receptor Antagonists(1)

Supporting Info

Lak Shin Jeong*^†, Shantanu Pal^†, Seung Ah Choe^†, Won Jun Choi^†, Kenneth A. Jacobson^‡, Zhan-Guo Gao^‡, Athena M. Klutz^‡, Xiyan Hou^†, Hea Ok Kim^†, Hyuk Woo Lee^†, Sang Kook Lee^†, Dilip K. Tosh^† and Hyung Ryong Moon^§

Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea, Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, College of Pharmacy, Pusan National University, Busan 609−753, Korea

J. Med. Chem., 2008, 51 (20), pp 6609–6613

DOI: 10.1021/jm8008647

Publication Date (Web): September 24, 2008

* To whom correspondence should be addressed. Phone: 82-2-3277-3466. Fax: 82-2-3277-2851. E-mail: lakjeong@ewha.ac.kr.

†

Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University.

‡

Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health.

College of Pharmacy, Pusan National University.

Abstract

Novel d- and l-4′-thioadenosine derivatives lacking the 4′-hydroxymethyl moiety were synthesized, starting from d-mannose and d-gulonic γ-lactone, respectively, as potent and selective species-independent A₃ adenosine receptor (AR) antagonists. Among the novel 4′-truncated 2-H nucleosides tested, a N⁶-(3-chlorobenzyl) derivative 7c was the most potent at the human A₃ AR (K_i = 1.5 nM), but a N⁶-(3-bromobenzyl) derivative 7d showed the optimal species-independent binding affinity.

View: Full Text HTML | Hi-Res PDF | PDF w/ Links

Tools

SciFinder Links

History

Published In Issue October 23, 2008
Article ASAPSeptember 24, 2008
Received: July 14, 2008

Recommend & Share

Related Content

Lead Optimization of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A_2A Adenosine Receptor Antagonists for the Treatment of Parkinson’s DiseaseJournal of Medicinal Chemistry
- Lead Optimization of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A_2A Adenosine Receptor Antagonists for the Treatment of Parkinson’s Disease
  Xiaohu Zhang, John E. Tellew, Zhiyong Luo, Manisha Moorjani, Emily Lin, Marion C. Lanier, Yongsheng Chen, John P. Williams, John Saunders, Sandra M. Lechner, Stacy Markison, Tanya Joswig, Robert Petroski, Jaime Piercey, William Kargo, Siobhan Malany, Mark Santos, Raymond S. Gross, Jenny Wen, Kayvon Jalali, Zhihong O’Brien, Carol E. Stotz, Mara I. Crespo, Jos-Luis Daz and Deborah H. Slee
  Journal of Medicinal Chemistry 2008 51 (22), pp 7099–7110
  Abstract: 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-pyrimidines bearing substituted pyridyl groups as C-6 substituents were prepared as selective adenosine hA_2A receptor antagonists for the treatment of Parkinson’s disease. The 5-methoxy-3-pyridyl derivative 6g (...
  Abstract | Full Text HTML | PDF w/ Links | Hi-Res PDF
Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H₄ Receptor LigandsJournal of Medicinal Chemistry
- Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H₄ Receptor Ligands
  Robert J. Altenbach, Ronald M. Adair, Brian M. Bettencourt, Lawrence A. Black, Shannon R. Fix-Stenzel, Sujatha M. Gopalakrishnan, Gin C. Hsieh, Huaqing Liu, Kennan C. Marsh, Michael J. McPherson, Ivan Milicic, Thomas R. Miller, Timothy A. Vortherms, Usha Warrior, Jill M. Wetter, Neil Wishart, David G. Witte, Prisca Honore, Timothy A. Esbenshade, Arthur A. Hancock, Jorge D. Brioni and Marlon D. Cowart
  Journal of Medicinal Chemistry 2008 51 (20), pp 6571–6580
  Abstract: A series of 2-aminopyrimidines was synthesized as ligands of the histamine H₄ receptor (H₄R). Working in part from a pyrimidine hit that was identified in an HTS campaign, SAR studies were carried out to optimize the potency, which led to compound 3, 4-...
  Abstract | Full Text HTML | PDF w/ Links | Hi-Res PDF
Synthesis and Structure−Activity Relationship Studies of Highly Potent Novel Oxazolidinone AntibacterialsJournal of Medicinal Chemistry
- Synthesis and Structure−Activity Relationship Studies of Highly Potent Novel Oxazolidinone Antibacterials
  Takashi Komine, Akihiko Kojima, Yoshikazu Asahina, Tatsuhiro Saito, Hisashi Takano, Taku Shibue and Yasumichi Fukuda
  Journal of Medicinal Chemistry 2008 51 (20), pp 6558–6562
  Abstract: Novel antibacterial biaryl oxazolidinones bearing an aza-, an oxa-, or a thiabicyclo[3.1.0]hex-6-yl ring system were synthesized, and their in vitro antibacterial activity and structure−activity relationships (SAR) were evaluated. Most of the synthesized ...
  Abstract | Full Text HTML | PDF w/ Links | Hi-Res PDF

Brief Article

Structure−Activity Relationships of Truncated d- and l-4′-Thioadenosine Derivatives as Species-Independent A₃ Adenosine Receptor Antagonists(1)