Cyclopentenylcytosine. A carbocyclic nucleoside with antitumor and antiviral properties

1988 ◽  
Vol 31 (9) ◽  
pp. 1687-1694 ◽  
Author(s):  
Victor E. Marquez ◽  
Mu Ill Lim ◽  
Susan P. Treanor ◽  
Jacqueline Plowman ◽  
Matthew A. Priest ◽  
...  
Keyword(s):  
Carbocyclic Nucleoside

scholarly journals 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity.

1997 ◽  
Vol 41 (5) ◽  
pp. 1082-1093 ◽  
Author(s):  
S M Daluge ◽  
S S Good ◽  
M B Faletto ◽  
W H Miller ◽  
M H St Clair ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Oral Bioavailability ◽  
Human Peripheral Blood ◽  
Cross Resistance ◽  
Immunodeficiency Virus ◽  
Carbocyclic Nucleoside ◽  
Hiv 1 ◽  
In Cells

1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile giving potent, selective anti-human immunodeficiency virus (HIV) activity. 1592U89 was selected after evaluation of a wide variety of analogs containing a cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides, optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'-deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23 microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold) with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB). 1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only triphosphate found in cells incubated with 1592U89 was that of the guanine analog (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and toxicological profiles of 1592U89 were distinct from and improved over those of CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM) and human leukemic and liver tumor cell lines. 1592U89 had excellent oral bioavailability (105% in the rat) and penetrated the CNS (rat brain and monkey cerebrospinal fluid) as well as AZT. Having demonstrated an excellent preclinical profile, 1592U89 has progressed to clinical evaluation in HIV-infected patients.

Synthesis of novel racemic carbocyclic nucleoside analogues derived from 4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol and 4-oxatricyclo[4.3.1.03,7]decane-10-methanol, compounds with activity against Coxsackie viruses

2009 ◽  
Vol 74 (3) ◽  
pp. 469-485 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Martin Dračínský ◽  
Armando M. De Palma ◽  
Johan Neyts ◽  
Antonín Holý
Keyword(s):  
Alder Reaction ◽  
Diels Alder ◽  
Purine Nucleoside ◽  
Nucleoside Analogues ◽  
Lithium Aluminium Hydride ◽  
Subsequent Reduction ◽  
Lithium Aluminium ◽  
Diels Alder Reaction ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

(1R*,2R*,3R*,4S*)-7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dimethanol (10) and (1R*,2R*,3R*,4S*)-bicyclo[2.2.2]oct-5-ene-2,3-dimethanol (14), which were prepared by the Diels–Alder reaction and subsequent reduction with lithium aluminium hydride, were treated with benzyl azidoformate to give benzylN-[(1R*,2R*,3S*,6S*,7S*,9S*)-9-(hydroxymethyl)-4,8-dioxatricyclo[4.2.1.03,7]nonan-2-yl]carbamate (11) and benzylN-[(1R*,2R*,3R*,6R*,7S*,10S*)-10-(hydroxymethyl)-4-oxatricyclo[4.3.1.03,7]decan-2-yl]carbamate (15). Hydrogenolysis of carbamates11or15afforded (1R*,2R*,3S*,6S*,7S*,9S*)-2-amino-4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol (12) or (1R*,2R*,3R*,6R*,7S*,10S*)-2-amino-4-oxatricyclo[4.3.1.03,7]decane-10-methanol (16). The amines12and16were transformed to thymine and purine nucleoside analogues. The target compounds were tested for the activity againstCoxsackievirus.

Design, synthesis, and anti-HIV activity of 4′-modified carbocyclic nucleoside phosphonate reverse transcriptase inhibitors

2009 ◽  
Vol 17 (4) ◽  
pp. 1739-1746 ◽  
Author(s):  
Constantine G. Boojamra ◽  
Jay P. Parrish ◽  
David Sperandio ◽  
Ying Gao ◽  
Oleg V. Petrakovsky ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Reverse Transcriptase Inhibitors ◽  
Design Synthesis ◽  
Carbocyclic Nucleoside ◽  
Anti Hiv

ChemInform Abstract: Unsaturated and Carbocyclic Nucleoside Analogues: Synthesis, Antitumor, and Antiviral Activity.

ChemInform ◽  
2010 ◽  
Vol 22 (24) ◽  
pp. no-no
Author(s):  
S. PHADTARE ◽  
D. KESSEL ◽  
T. H. CORBETT ◽  
H. E. RENIS ◽  
B. A. COURT ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Nucleoside Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

Regioselective Coupling of Tetraalkylammonium Salts of 6-Iodo-2-aminopurine to a Cyclobutyl Triflate: Efficient Preparation of Homochiral BMS-180,194, a Potent Antiviral Carbocyclic Nucleoside

1995 ◽  
Vol 60 (9) ◽  
pp. 2902-2905 ◽  
Author(s):  
Gregory S. Bisacchi ◽  
Janak Singh ◽  
Jollie D. Godfrey ◽  
Thomas P. Kissick ◽  
Toomas Mitt ◽  
...  
Keyword(s):  
Tetraalkylammonium Salts ◽  
Carbocyclic Nucleoside

scholarly journals #Nitrosocarbonyls 1: Antiviral Activity ofN-(4-Hydroxycyclohex-2-en-1-yl)quinoline-2-carboxamide against the Influenza A Virus H1N1

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Dalya Al-Saad ◽  
Misal Giuseppe Memeo ◽  
Paolo Quadrelli
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Small Molecules ◽  
Influenza A ◽  
Nucleoside Analogues ◽  
Virus H1n1 ◽  
Antiviral Activities ◽  
Synthetic Approaches ◽  
Carbocyclic Nucleoside

Influenza virus flu A H1N1 still remains a target for its inhibition with small molecules. Fleeting nitrosocarbonyl intermediates are at work in a short-cut synthesis of carbocyclic nucleoside analogues. The strategy of the synthetic approaches is presented along with thein vitroantiviral tests. The nucleoside derivatives were tested for their inhibitory activity against a variety of viruses. Promising antiviral activities were found for specific compounds in the case of flu A H1N1.

An application of quinic acid to the synthesis of cyclic homochiral molecules: A common route to some interesting carbocyclic nucleoside precursors.

1993 ◽  
Vol 34 (49) ◽  
pp. 7985-7988 ◽  
Author(s):  
Christopher D. Maycock ◽  
M.Teresa Barros ◽  
António G. Santos ◽  
Lício S. Godinho
Keyword(s):  
Quinic Acid ◽  
Carbocyclic Nucleoside

ChemInform Abstract: Asymmetric Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Potential Antiviral and Antitumor Agent

ChemInform ◽  
2008 ◽  
Vol 39 (11) ◽  
Author(s):  
Lak Shin Jeong ◽  
Jeong A. Lee ◽  
Hyung Ryong Moon ◽  
Hea Ok Kim ◽  
Kang Man Lee ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Antitumor Agent ◽  
Nucleoside Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

A Novel Approach to Khantiokerically Pure Carbocyclic Nucleoside Analogues

1987 ◽  
Vol 6 (1-2) ◽  
pp. 233-237 ◽  
Author(s):  
Michael Bodenteich ◽  
Kurt Faber ◽  
Gerhard Penn And ◽  
Herfried Griengl
Keyword(s):  
Nucleoside Analogues ◽  
Novel Approach ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues

Asymmetric Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Potential Antiviral and Antitumor Agent

2007 ◽  
Vol 26 (6-7) ◽  
pp. 721-724 ◽  
Author(s):  
Lak Shin Jeong ◽  
Jeong A. Lee ◽  
Hyung Ryong Moon ◽  
Hea Ok Kim ◽  
Kang Man Lee ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Antitumor Agent ◽  
Nucleoside Analogues ◽  
Carbocyclic Nucleoside ◽  
Carbocyclic Nucleoside Analogues
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