Synthesis and biological activity of 4-amino-1-(β-D- ribofuranosyl)imidazo[4,5-d]pyridazin-7-one

Article abstract of DOI:10.1080/15257779408010678

The Lewis acid catalyzed ribosylation of 5(4)-cyano-4(5)-(5-methyl-1,2,4- oxadiazol-3-yl)-1H-imidazole (2) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D- ribose gave only 4-(5-methyl-1,2,4-oxadiazol-3-yl)-1-(2,3,5-tri-O-benzoyl- β-D-ribofuranosyl)imidazole-5-carbonitrile (3). Treatment of 3 with methanolic ammonia gave 4-(5-methyl-1,2,4-oxadiazol-3-yl)-1-(β-D- ribofuranosyl)imidazole-5-carbonitrile (4). Treatment of 4 with hydrogen peroxide in ammonia gave 4-(5-methyl-1,2,4-oxadiazol-3-yl)-1 (β-D- ribofuranosyl)imidazole-5-carboxamide (5). When 5 was treated with sodium hydride in dimethyl-sulfoxide a rearrangement (mononuclear heterocyclic rearrangement, m.h.r.) occurred to give a modest 17% yield of 4-acetamido-1- (β-D-ribofuranosyl)imidazo[4,5-d]pyridazin-7-one (6). Treatment of 6 with aqueous ammonia gave 4-amino-1-(β-D-ribofuranosyl)imidazo[4,5-d]pyridazin- 7-one (1). The synthesis of compound 1 using the m.h.r. for the preparation of a single regioisomer of the imidazo[4,5-d]pyridazin-7-one ring system, has demonstrated the potential of this methodology. Neither compound 5 nor 6 affected the growth or replication of human foreskin fibroblasts (HFF cells) or human cytomegalovirus (HCMV). In contrast, compound I inhibited the replication of HCMV (IC₅₀=29 μM) but produced visual cytotoxicity in uninfected HFF cells (IC₅₀=70μM). Compound I also inhibited the proliferation of L1210 murine leukemic cells (IC₅₀=25 μM), whereas the precursors 4 and 6 did not.

Full text of DOI:10.1080/15257779408010678

This article was downloaded by: [University of Chicago Library]
On: 10 October 2014, At: 15:51
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Nucleosides and Nucleotides
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lncn19
Synthesis and Biological Activity of 4-
Amino-1-(β-D-ribofuranosyl)imidazo[4,5-
d]pyridazin-7-one
David A. Berry a b c d , Linda L. Wotring a b c d , John C. Drach a b c d
& Leroy B. Townsend a b c d
a Department of Medicinal Chemistry , College of Pharmacy , Ann
Arbor, 48109-1065
b Department of Pharmaceutical Chemistry , College of Pharmacy ,
Ann Arbor, 48109-1065
c Department of Chemistry , College of Literature, Sciences, and
Arts , Ann Arbor, 48109-1065
d Department of Biologic and Materials Sciences , School of
Dentistry, University of Michigan , Ann Arbor, 48109-1065
Published online: 24 Sep 2006.
To cite this article: David A. Berry , Linda L. Wotring , John C. Drach & Leroy B. Townsend (1994)
Synthesis and Biological Activity of 4-Amino-1-(β-D-ribofuranosyl)imidazo[4,5-d]pyridazin-7-one,
Nucleosides and Nucleotides, 13:9, 2001-2011, DOI: 10.1080/15257779408010678
To link to this article: http://dx.doi.org/10.1080/15257779408010678
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions