| 1. |
- Artacho Ruiz, Josep, et al.
(författare)
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The synthesis and characterization of all diastereomers of a linear symmetrically fused tris-Troger's base analogue: New chiral cleft compounds
- 2006
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Ingår i: Chemistry: A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 12:10, s. 2692-2701
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and characterization of all diastereomers of a linear symmetrically fused tris-Troger's base analogue are described. The diastereomers are unambiguously assigned as syn-anti 1a, anti-anti 1b, and syn-syn 1c isomers, by using X-ray diffraction analysis and NMR spectroscopy. For the first time, the anti-anti and the syn-syn diastereomers of a linear symmetrically fused tris-Troger's base analogue have been synthesized. Molecules 1a and 1c are new cleft compounds and analysis of compound 1a in the solid state shows inclusion of one molecule of CH2Cl2 in the larger aromatic cleft, whereas in isomer 1c disordered solvent molecules are trapped in the extended aromatic cleft. Furthermore, in the solid state, isomer 1c forms infinite open channels along one of the crystallographic axes and perpendicular to this axis there are infinitely extending "wedged-ravines". Importantly, each of the diastereomers 1a-c is resistant to inversion at the stereogenic nitrogen atoms under strongly and weakly acidic conditions in the range from room temperature (RT) to 95 degrees C. This observed configurational stability at the stereogenic nitrogens of 1a-c is unique for analogues of Troger's base in general to date. Finally, the ratio of cleft compounds 1a and 1c significantly increased relative to cavity compound 1b when ammonium chloride was used as an additive in the Troger's base condensation to 1a-c suggesting a templating effect of the ammonium ion.
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| 2. |
- Mårtensson, Ulrika, et al.
(författare)
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Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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