- Peptide deformylase inhibitors
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The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhibition of bacterial peptide deformylase (PDF) activity.
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Page/Page column
(2014/12/09)
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- PEPTIDE DEFORMYLASE INHIBITORS
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The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhi-bition of bacterial peptide deformylase (PDF) activity
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Page/Page column
(2014/02/15)
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- 8-(2-Furyl)adenine derivatives as A2A adenosine receptor ligands
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Selective adenosine receptor modulators are potential tools for numerous therapeutic applications, including cardiovascular, inflammatory, and neurodegenerative diseases. In this work, the synthesis and biological evaluation at the four human adenosine receptor subtypes of a series of 9-substituted 8-(2-furyl)adenine derivatives are reported. Results show that 8-(2-furyl)-9-methyladenine is endowed with high affinity at the A2A subtype. Further modification of this compound with introduction of arylacetyl or arylcarbamoyl groups in N6-position takes to different effects on the A2A affinity and in particular on the selectivity versus the other three adenosine receptor subtypes. A molecular modelling analysis at three different A2A receptor crystal structures provides an interpretation of the obtained biological results.
- Dal Ben, Diego,Buccioni, Michela,Lambertucci, Catia,Thomas, Ajiroghene,Klotz, Karl-Norbert,Federico, Stephanie,Cacciari, Barbara,Spalluto, Giampiero,Volpini, Rosaria
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p. 525 - 535
(2013/11/19)
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- 8-Bromo-9-alkyl adenine derivatives as tools for developing new adenosine A2A and A2B receptors ligands
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Importance of making available selective adenosine receptor antagonists is boosted by recent findings of adenosine involvement in many CNS dysfunctions. In the present work a series of 8-bromo-9-alkyl adenines are prepared and fully characterized in radio
- Lambertucci, Catia,Antonini, Ippolito,Buccioni, Michela,Dal Ben, Diego,Kachare, Dhuldeo D.,Volpini, Rosaria,Klotz, Karl-Norbert,Cristalli, Gloria
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experimental part
p. 2812 - 2822
(2009/09/08)
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- Purines. LXXV. Dimroth rearrangement, hydrolytic deamination, and pyrimidine-ring breakdown of 7-alkylated 1-alkoxyadenines: N(1)-C(2) versus N(1)-C(6) bond fission
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On treatment with boiling H2O for 5-6h, 1-alkoxy-7-alkyladenines (13) underwent hydrolytic cleavage of the N(1)-C(2) and the N(1)-C(6) bonds to produce the imidazole-5-carboxamidines (14) in 53-60% yields and the imidazole-5-carboxamides (18) i
- Itaya, Taisuke,Ito, Nobuaki,Kanai, Tae,Fujii, Tozo
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p. 832 - 841
(2007/10/03)
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- Electrophilic amination of adenines. Formation and characteristics of N-aminoadenines
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Amination of adenine with H2N-O-SO3H in alkaline media afforded 1-, 3-, 7- and 9-aminoadenine isomers at a ratio of about 1:1:3:1. In neutral media, the product ratio of the isomers changed to about 3:1:1:0. These results were different from the regioselectivity obtained by methylation of adenine with dimethyl sulfate under similar conditions. Amination of adenine with dinitrophenoxyamine in DMF gave 1-aminoadenine as the main product and this regioselectivity was also different from that of methylation with CH3I. Chemical characteristics of these N-amino adenines are described.
- Saga, Tetsuya,Kaiya, Toyo,Asano, Shoji,Kohda, Kohfuku
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p. 219 - 233
(2007/10/03)
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- Purines. LXI. An attempted synthesis of 2'-deoxy-7-methyladenosine: Glycosidic hydrolyses of the N6-methoxy derivative and 2'-deoxy-N(x)- methyladenosines
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In an attempt to synthesize 2'-deoxy-7-methyladenosine (5b), 2'-deoxy- N6-methoxyadenosine (13b) was treated with MeI in AcNMe2 at 0°C for 7h to give the 2'-deoxy-N6-methoxy-7-methyladenosine salt (14b), which was unstable and easily underwent glycosidic hydrolysis in H2O at 16-18°C to form N6-methoxy-7-methyladenine (15). On account of such instability, hydrogenolysis of 14b in H2O using hydrogen and Raney Ni catalyst failed to afford the desired nucleoside (5b). 2'-Deoxy-N6-methyladenosine (2b), 2'- deoxy-1-methyladenosine (3b), and 14b were found to undergo glycosidic hydrolysis in 0.1 N aqueous HCl at 25°C at rates of 7.92 x 10-2 min-1 (half-life 87.5 min), 5.02 x 10-3min-1 (half-life 138 min), and 2.31 x 10-2 min-1 (half-life 30.0 min), respectively, while the rate in the case of 5h was roughly estimated to be ca. 2 min-1 (half-life 0.35 min).
- Fujii,Saito,Iguchi
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p. 495 - 499
(2007/10/02)
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- The Prominent Effect of N6-Acyl Groups on the Reactivity of 9-Substituted Adenines: A New Method for the Chemical Modification of Adenines
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The effect of various N6-substituents on the C(8)-hydrogen exchange of 9-substituted adenines has been estimated.The kinetic data clearly demonstrate that the N6-acyl groups significantly accelerate the C(8)-hydrogen exchange.This fa
- Maki, Yoshifumi,Kameyama, Keiji,Suzuki, Mikio,Sako, Magoichi,Hirota, Kosaku
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p. 3601 - 3654
(2007/10/02)
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- Heterocyclic Ambident Nucleophiles. III* The Alkylation of Sodium Adenide
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The alkylation of sodium adenide in HCONMe2 (30 deg) with various alkylating agents was analysed by 1H n.m.r. spectroscopy.Widely varying N3:N7:N9 alkylation patterns were observed, depending on the alkylating agent.These patterns are interpreted in terms of the electrostatic, thermodynamic and steric factors involved in the different SN2 transition states appropriate to each alkylating agent.Hydrogen bonding association between the 6-amino group and certain carbonyl containing alkylating agents is proposed to explain the enhancedN7-alkylation in some cases.Support for this latter proposal was obtain from a comparison of the adenine alkylation results with the corresponding alkylation patterns of 6-pivaloylamino- and 6-chloro-purine.
- Rasmussen, Malcolm,Hope, Janet M.
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p. 525 - 534
(2007/10/02)
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- SYNTHESIS AND GLYCOSIDIC BOND CLEAVAGE OF 7-METHYL- AND 7-ETHYL-ADENOSINES: AN ALTERNATIVE SYNTHESIS OF 7-ALKYLADENINES
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7-Methyladenosine perchlorate (VIIa: X = ClO4) was prepared in pure and crystalline form from N6-methoxyadenosine (I) by methylation with MeI at the 7-position followed by catalytic hydrogenolysis of the N6-methoxy group. 7-Ethyladenosine perchlorate (VIIb: X = ClO4) was also synthesized from N6-benzyloxyadenosine (II) in an analogous manner.On treatment with H2O at 98-100 deg C for 40 min, VIIa (X = ClO4) and VIIb (X = ClO4) produced 7-methyladenine (VIIIa) and 7-ethyladenine (VIIIb) in 84percent and 55percent yields.In 0.1 N aqueous HCl at 25 deg C, VIIa (X = ClO4) and VIIb (X = ClO4) were hydrolyzed in similar manners at rates of 2.22E-3 min-1 and 1.69E-3 min-1, respectively.Comparison of these rate conctants with those of other three N-methyladenosine isomers X, XI, and XII has revealed that the relative ease of the hydrolysis of the glycosidic bond is in the order of 3- (XI) > 7- (VIIa) >> N6- (X) >/= 1-methyladenosine (XII).
- Fujii, Tozo,Saito, Tohru
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p. 117 - 123
(2007/10/02)
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