- Understanding the Conformational Behavior of Fluorinated Piperidines: The Origin of the Axial-F Preference
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Gaining an understanding of the conformational behavior of fluorinated compounds would allow for expansion of the current molecular design toolbox. In order to facilitate drug discovery efforts, a systematic survey of a series of diversely substituted and protected fluorinated piperidine derivatives has been carried out using NMR spectroscopy. Computational investigations reveal that, in addition to established delocalization forces such as charge–dipole interactions and hyperconjugation, solvation and solvent polarity play a major role. This work codifies a new design principle for conformationally rigid molecular scaffolds.
- Nairoukh, Zackaria,Strieth-Kalthoff, Felix,Bergander, Klaus,Glorius, Frank
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p. 6141 - 6146
(2020/05/18)
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- A practical synthesis of enantiopure 7-alkoxy-4-aryl- tetrahydroisoquinoline, a dual serotonin reuptake inhibitor/histamine H 3 antagonist
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An efficient synthesis of compound 1 featuring a novel sequential Friedel-Crafts alkylation strategy to construct the 4-aryl- tetrahydroisoquinoline core structure has been developed. Resolution with (D/L)-di-p-toluoyl-tartaric acid is utilized to provide the enantiomerically pure material. Overall, the route is concise and amenable for large-scale synthesis.
- Deng, Xiaohu,Liang, Jimmy T.,Liu, Jing,McAllister, Heather,Schubert, Garsten,Mani, Neelakandha S.
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p. 1043 - 1050
(2012/12/30)
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- INHIBITORS OF 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE 1
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The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salts or solvates thereof, wherein n, X, Y, R1, R2, R3 and R4 are as described in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating conditions that are mediated by the modulation of 11 βHSD1 , the method comprising administering to a mammal an effective amount of a compound of formula (I).
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Page/Page column 45
(2010/11/25)
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- CYCLOHEXYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel cyclohexylalanine derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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- γ-amino-substituted analogues of 1-[(S)-2,4-diaminobutanoyl]piperidine as highly potent and selective dipeptidyl peptidase II inhibitors
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Using 1-[(S)-2,4-diaminobutanoyl]piperidine as lead compound, we developed a large series of highly potent and selective dipeptidyl peptidase II (DPP II) inhibitors. γ-Amino substitution with arylalkyl groups, for example, a 2-chlorobenzyl moiety, resulted in a DPP II inhibitor with an IC50 = 0.23 nM and a high selectivity toward DPP IV (IC50 = 345 μM). Furthermore, it was shown that the basicity of the γ-amino is important and that α-amino substitution is not favorable. Piperidine-2-nitriles did not show an increase in potency but rather reduced the selectivity. Introduction of a 4-methyl or a 3-fluorine on piperidine improved selectivity and preserved the high potency.
- Senten, Kristel,Van Der Veken, Pieter,De Meester, Ingrid,Lambeir, Anne-Marie,Scharpé, Simon,Haemers, Achiel,Augustyns, Koen
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p. 2906 - 2916
(2007/10/03)
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