- Synthesis and evaluation of novel ligands for the histamine H4 receptor based on a pyrrolo[2,3-d]pyrimidine scaffold
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Starting from a known H4R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH4R (Ki = 0.5 μM), its lacks selectivity with a K i value for the hH3R of 1 μM. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show Ki values of less than 1 μM at the hH4R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH4R ligands.
- Gao, Ling-Jie,Schwed, J. Stephan,Weizel, Lilia,De Jonghe, Steven,Stark, Holger,Herdewijn, Piet
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p. 132 - 137
(2013/02/23)
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- Novel angular benzophenazines: Dual topoisomerase I and topoisomerase II inhibitors as potential anticancer agents
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A series of substituted angular benzophenazines were prepared using a new synthetic route via a novel regiocontrolled condensation of 1,2-naphthoquinones and 2,3-diaminobenzoic acids. The synthesis and biological activity of this new series of substituted
- Vicker, Nigel,Burgess, Luke,Chuckowree, Irina S.,Dodd, Rory,Folkes, Adrian J.,Hardick, David J.,Hancox, Timothy C.,Miller, Warren,Milton, John,Sohal, Sukhjit,Wang, Shouming,Wren, Stephen P.,Charlton, Peter A.,Dangerfield, Wendy,Liddle, Chris,Mistry, Prakash,Stewart, Alistair J.,Denny, William A.
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p. 721 - 739
(2007/10/03)
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- An efficient conversion of chiral α-amino acids to enantiomerically pure 3-amino cyclic amines
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Enantiomerically pure 3-amino cyclic amines such as 3-amino pyrrolidine, 3-amino piperidine, and 2,3,4,5,6,7-hexahydro-1H-azepine have been synthesized in high yields from the optically active natural α-amino acids such as L-aspartic acid, L-glutamic acid, L-2-aminoadipic acid, and their enantiomers.
- Moon, Sung-Hwan,Lee, Sujin
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p. 3919 - 3926
(2007/10/03)
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- Quinobenzoxazine, antineoplastic agents
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Quinobenzoxazine, derivatives of the formula STR1 as well as the pharmaceutically acceptable salts, esters, amides and prodrugs thereof are disclosed, wherein R1 is hydrogen or a carboxy-protecting group, R2 and R3 are substitutents, A is oxygen, Z is a halogen or a nitrogen-containing group, X is hydrogen, halogen or alkyl, and W is hydrogen, alkyl, amino or halogen. The compounds have potent antineoplastic activity.
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- Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3- amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity
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A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1- pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl- 6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3- quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3- quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparative solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S- (R*,R*)]-7-[3-[(2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl- 6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).
- Sanchez,Domagala,Heifetz,Priebe,Sesnie,Trehan
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p. 1764 - 1773
(2007/10/02)
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- (S)-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid
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The novel (S)-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-n phthyridine-3-carboxylic acid, lower alkyl esters and pharmaceutically acceptable salts thereof are described as well as a method for its manufacture, formulation, and use in treating bacterial infections.
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- Naphthyridine antibacterial agents containing an α-amino acid in the side chain of the 7-substituent
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Novel quinolone and naphthyridine antibacterial agents are herein described having improved in vivo activity both orally and subcutaneously where the 7-side chain of such compounds contain an α-amino acid; also described are its corresponding optical isomers, methods of preparation as well as compositions and methods of treating infections diseases.
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