43077-06-1Relevant articles and documents
Species- or Isozyme-Specific Enzyme Inhibitors. 7. Selective Effects in Inhibition of Rat Adenylate Kinase Isozymes by Adenosine 5'-Phosphate Derivatives.
Hai, Ton T.,Picker, Donald,Abo, Masanobu,Hampton, Alexander
, p. 806 - 812 (1982)
Monosubstituted derivatives of adenosine 5'-phosphate (AMP) with substituents of 1-3 atoms or group replacements at any of 11 positions have been synthesized and examined as substrates and inhibitors of the rat muscle adenylate kinase isozyme (AK-M), and the rat AK II and III isozymes predominant in poorly differentiated hepatoma tissue and normal liver tissue, respectively.Inhibition indexes of the compounds were expressed as KM(AMP)/Ki for competitive inhibition or as KM (AMP)/KM when only KM was available.Substituents at N(1), N6, or C(8) or on ionizable phosphate oxygen reduced inhibition below measurable levels; 2'-deoxy-AMP and adenosine 5'-sulfate had identical inhibition indexes with all three isozymes; compounds with substituents at C(2), O(2'), O(3'), C(4'), C(5'), or O(5') had higher inhibition indexes with AK-M than with AK II or III and the same or similar indexes for AK II and III.The most effective and / or selective inhibitors were 2-NHMe-AMP (index with AK-M, 0.2; index ratio, AK-M/AK III, 9.1), 2'-O-Me-AMP (index with AK-M, 0.14; index ratio, AK-M/AK III, 8.2), 2',3'-O-CMe2-AMP (index with AK-M, 0.25; index ratio, AK-M/AK II, 6.6), 4'-allyl-AMP (index with AK-M, 0.97; index ratio, AK-M/AK III, 8.1), and 5'(S)-Et-AMP (index with AK-M, 0.64; index ratio, AK-M/AK II, 11.2).The study provides additional evidence that the attachment of simple substituents to various atoms in turn of a substrate is a potentially useful approach in early stages of the attempted design of isozyme-selective inhibitors.
PROTEIN ARGININE N-METHYLTRANSFERASES INHIBITORS AND USES THEREOF
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Page/Page column 21; 33; 34; 35, (2018/01/15)
The present invention relates to a compound of following formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, notably for use thereof as a drug, notably in the treatment of cancer, or as a PRMT inhibitor. The present invention relates also to a pharmaceutical composition containing such a compound and to a method for the preparation of such a compound.
Hemisynthesis of deuteriated adenosylhopane and conversion into bacteriohopanetetrol by a cell-free system from Methylobacterium organophilum
Liu, Wenjun,Bodlenner, Anne,Rohmer, Michel
supporting information, p. 3393 - 3405 (2015/03/18)
Adenosylhopane is a putative precursor of the widespread bacterial C35 biohopanoids. A concise and flexible hemisynthesis of adenosylhopane has been developed including as key steps a cross metathesis between two olefins containing either the h
Analogues of the natural product sinefungin as inhibitors of EHMT1 and EHMT2
Devkota, Kanchan,Lohse, Brian,Liu, Qing,Wang, Ming-Wei,Staerk, Dan,Berthelsen, Jens,Clausen, Rasmus Praetorius
supporting information, p. 293 - 297 (2014/05/06)
A series of analogues of the natural product sinefungin lacking the amino acid moiety was synthesized and probed for their ability to inhibit EHMT1 and EHMT2. This study led to inhibitors 3b and 4d of methyltransferase activity of EHMT1 and EHMT2 and it demonstrates that such analogues constitute an interesting scaffold to develop selective methyltransferase inhibitors. Surprisingly, the inhibition was not competitive toward AdoMet.
Synthesis of 5′-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5′ and sulfur atoms replaced by a vinyl or halovinyl unit
Wnuk, Stanislaw F.,Sacasa, Pablo R.,Lewandowska, Elzbieta,Andrei, Daniela,Cai, Sumin,Borchardt, Ronald T.
, p. 5424 - 5433 (2008/12/21)
Adenosine and uridine analogues functionalized with alkenyl or fluoroalkenyl chain at C5′ were prepared employing cross-metathesis, Negishi couplings, and Wittig reactions. Metathesis of the protected 5′-deoxy-5′-methyleneadenosine or uridine analogues wi
Nucleoside 5′-C-phosphonates: reactivity of the α-hydroxyphosphonate moiety
Králíková, ?árka,Budě?ínky, Milo?,Masojídková, Milena,Rosenberg, Ivan
, p. 4917 - 4932 (2007/10/03)
We found that various dialkyl phosphites, dialkyl trimethylsilyl phosphites, and tris-trimethylsilyl phosphite reacted smoothly with nucleoside 5′-aldehydes to afford epimeric nucleoside 5′-C-phosphonates in high yields. A number of these compounds in bot
Stereoselective adenylate deaminase (5′-adenylic acid deaminase, AMPDA)-catalyzed deamination of 5′-alkyl substituted adenosines: A comparison with the action of adenosine deaminase (ADA)
Ciuffreda, Pierangela,Loseto, Angela,Santaniello, Enzo
, p. 203 - 206 (2007/10/03)
The enzymes adenylate deaminase (AMPDA) and adenosine deaminase (ADA) are able to catalyze the stereoselective hydrolytic deamination of (5′R,S)-methyl-2′,3′-isopropylidene adenosine, but the 5′-butyl analog is a substrate only for AMPDA, which stereospec
Oligonucleosides with a nucleobase-including backbone: Part 12 - Synthesis of mixed ethynylene-linked uridine- and adenosine-derived tetramers
Eppacher, Simon,Bhardwaj, Punit Kumar,Bernet, Bruno,Gala, Jose Luis Bravo,Knoepfel, Thomas,Vasella, Andrea
, p. 2969 - 2986 (2007/10/03)
In contradistinction to the corresponding Grignard reagent, bis[(trimethylsilyl)ethynyl]zinc reacted with the 5′-oxoadenosine 3 diastereoselectively to the β-D-allo-hept-6-ynofuranosyladenine 5. Lithiation/iodination of the monomeric propargyl alcohol 5 a
Sugar-modified conjugated diene analogues of adenosine and uridine: Synthesis, interaction with S-adenosyl-L-homocysteine hydrolase, and antiviral and cytostatic effects
Wnuk, Stanislaw F.,De Clercq, Erik,Ro, Bong-Oh,Valdez, Carlos A.,Lewandowska, Elzbieta,Valdez, Neida X.,Sacasa, Pablo R.,Yin, Dan,Zhang, Jinsong,Borchardt, Ronald T.
, p. 2651 - 2658 (2007/10/03)
Moffatt oxidation of 2′,3′-O-isopropylideneuridine (1a) and treatment of the crude 5′-aldehyde with formylmethylene-stabilized Wittig reagent gave the vinylogously extended 7′-aldehyde 2a. Condensation of 2a with ethoxycarbonyl- or dibromomethylene phosph
Oligonucleosides with a nucleobase-including backbone. Part 2. Synthesis and structure determination of adenosine-derived monomers
Gunji, Hiroki,Vasella, Andrea
, p. 1331 - 1345 (2007/10/03)
The synthesis and structure determination of adenosine-derived monomeric building blocks for new oligonucleosides are described. Addition of Me3Si- acetylide to the aldehyde derived from the known partially protected adenosine 1 led to the epimeric propargylic alcohols 2 and 3, which were oxidised to the same ketone 4, while silylation and deprotection led to 7 and 9 (Scheme 1). Introduction of an I substituent at C(8) of the propargylic silyl ethers 10 and 11 was not satisfactory. The protected adenosine 12 was, therefore, transformed in high yield into the 8-chloro derivative 13 by deprotonation and treatment with PhSO2CI; the iodide 15 was obtained in a similar way (Scheme 2). The 8-Cl and the 8-I derivatives 13 and 15 were transformed into the propargylic alcohols 17, 18, 25, and 26, respectively (Scheme 3). The propargylic derivatives 2, 10, 17, 19, 23, 25, and 27 were correlated, and their (5'R) configuration was determined on the basis of NOEs of the anhydro nucleoside 19; similarly, correlation of 3, 11, 18, 20, 24, 26, and 28, and NOE's of 20 evidenced their (5'S)-configuration.
