- COMPOUNDS AND COMPOSITIONS AS MODULATORS OF GPR119 ACTIVITY
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The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119.
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Page/Page column 127-128
(2009/04/25)
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- Process for making 3-amino-pyrolidine derivatives
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The invention is concerned with a process for making a compound of formula STR1 wherein R1 is hydrogen, alkyl, cyclo-alkyl, alkenyl, aryl or an amino protecting group; and R2, R3 each independently is hydrogen, alkyl, cyclo-alkyl, alkenyl or aryl; by reacting a compound of the formula STR2 wherein X is a protected hydroxy group; with R1 NH2 to form a compound of formula STR3 wherein X and R1 are described herein above; and then reacting the compound of formula III with R2 R3 NH under pressure to form the compound of formula I. These compounds are valuable intermediates useful in making cephalosporin derivatives.
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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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