180181-02-6Relevant articles and documents
Isotopically labelled and unlabelled β-peptides with geminal dimethyl substitution in 2-position of each residue: Synthesis and NMR investigation in solution and in the solid state
Seebach, Dieter,Sifferlen, Thierry,Bierbaum, Daniel J.,Rueping, Magnus,Jaun, Bernhard,Schweizer, Bernd,Schaefer, Jacob,Mehta, Anil K.,O'Connor, Robert D.,Meier, Beat H.,Ernst, Matthias,Glaettli, Alice
, p. 2877 - 2917 (2002)
The preparation of (S)-β2.2.3-amino acids with two Me groups in the α-position and the side chains of Ala, Val, and Leu in the β-position (double methylation of Boc-β-HAla-OMe, Boc-β-Val-OMe, and Boc-β-Leu-OMe, Scheme 2) is described. These β-amino acids and unlabelled as well as specifically 13C- and 15N-labelled 2,2-dimethyl-3-amino acid (β2.2-HAib) derivatives have been coupled in solution (Schemes 1, 3 and 4) to give protected (N-Boc, C-OMe), partially protected (N-Boc/C-OH, N-H/C-OMe), and unprotected β2.2- and β2.2.3.-hexapeptides, and β2.2- and β2.2.3-heptapeptides 1-7. NMR Analyses in solution (Tables 1 and 2, and Figs. 2-4) and in the solid state (2D-MAS NMR measurements of the fully labelled Boc-(β2.2-HAib)6-OMe ([13 C30, 15N6]-1e; Fig. 5), and TEDOR/REDOR NMR investigations of mixtures (Fig. 6) of the unlabelled Ac-(β2.2-HAib)7-OMe (4) and of a labelled derivative ([13C4,15N2]-5; Figs. 7-11, and 19), a molecular-modeling study (Figs. 13-15), and a search in the Cambridge Crystallographic Data Base (Fig. 16) allow the following conclusions: i) there is no evidence for folding (helix or turn) or for aggregation to sheets of the geminally dimethyl substituted peptide chains in solution; ii) there are distinct conformational preferences of the individual β2.2- and β2.2.3-amino acid residues: close to eclipsing around the C(O)-C(Me2(CHR)) bond (τ1.2), almost perfect staggering around the C(2)-C(3) ethane bond (τ2.3), and antiperiplanar arrangement of H(C3) and H(N) (τ3,N; Fig. 12) in the solid state; iii) the β2.2-peptides may be part of a turn structure with a ten-membered H-bonded ring; iv) the main structure present in the solid state of F3CCO(β2.2-HAib)7-OMe is a nonfolded chain (> 30 A between the termini and > 20 A between the N-terminus and the CH2 group of residue 5) with all C=O bonds in a parallel alignment (± 10°). With these structural parameters, a simple modelling was performed producing three (maybe four) possible chain geometries: one fully extended, two with parallel peptide planes (with zick-zack and crankshaft-type arrangement of the peptide bonds), and (possibly) a fourth with meander-like winding (D - G in Figs. 17 and 18).
NOVEL COMPOUND HAVING ABILITY TO INHIBIT 11B-HSD1 ENZYME OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, METHOD FOR PRODUCING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT
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, (2015/08/04)
The present invention relates to a novel compound or a pharmaceutically acceptable salt thereof inhibiting 11β-HSD1 enzyme activity, a preparation method of the same, and a pharmaceutical composition comprising the same as an active ingredient. Since the compound of the present invention selectively inhibits the activity of 11β-HSD1 (11β-Hydroxysteroid dehydrogenase type 1), the compound of the invention can be effectively used as a therapeutic agent for the treatment of diseases caused by the over-activation of 11β-HSD1 such as non-insulin dependent type II diabetes, insulin resistance, obesity, lipid disorder, metabolic syndrome, and other diseases or condition mediated by the excessive activity of glucocorticoid.
SELECTIVE CALCIUM CHANNEL MODULATORS
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Page/Page column 47, (2011/04/19)
Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted T- type calcium channel activity are disclosed using a series of compounds containing N-acylated cyclic amines linked to an aπl ring as shown in formula (I).
