127776-75-4Relevant academic research and scientific papers
Synthesis of iminodiacetaldehyde derivatives as building blocks for pharmacologically active agents
Fricke, Yvonne,Kopp, Nicole,Wuensch, Bernhard
, p. 791 - 796 (2010)
The preparation of iminodiacetaldehyde derivatives is reported via oxidative cleavage of 3,4-dihydroxypyrrolidines with sodium periodate. High yields of iminodiacetaldehydes are obtained starting from N-acyl-protected pyrrolidines, whereas the basic N-benzyl-protected derivative does not yield the expected dialdehyde. A cis-configured dihydroxypyrrolidine, prepared from 2,5-dihydropyrrole, reacts considerably faster with sodium periodate than the corresponding trans-configured derivatives which are obtained in three steps from (R,R)-tartaric acid. Georg Thieme Verlag Stuttgart.
Synthesis and pharmacological evaluation of conformationally restricted κ-opioid receptor agonists
Wenker, Yvonne,Soeberdt, Michael,Daniliuc, Constantin,St?nder, Sonja,Schepmann, Dirk,Wünsch, Bernhard
, p. 2368 - 2380 (2016)
In order to obtain novel polar κ agonists the κ-pharmacophoric ethylenediamine structural element was embedded in a rigid bicyclic scaffold. The pyridooxazine system was selected since it contains polar O- and N-atoms in the 1- and 7-positions, respectively. An axially oriented pyrrolidine ring was attached at the 5-position and the dichlorophenylacetyl moiety was introduced at N-4. The key steps of the 11-step synthesis are a double Henry reaction of iminodiacetaldehyde 7 with nitromethane and the introduction of the azido moiety of 13 by Mitsunobu reaction of the alcohol 11 with Zn(N3)2·(pyridine)2. The X-ray crystal structure analysis of 17b shows a dihedral angle N(acyl)-C-C-N(pyrrolidine) of ?60.8(2)°, which is close to the postulated optimal angle. Moderate κ affinity was found for the secondary amine 17a (Ki = 132 nM) and the methyl derivative 17b (Ki = 266 nM). In the [35S]GTPγS assay the secondary amine 17a showed 28% agonistic activity compared to U-69,593. Although 17a and 17b contain all crucial κ-pharmacophoric elements, their κ affinity is rather low, which might be attributed to the unfavorable cis-orientation of the pyrrolidine ring and the dichlorophenylacetamido moiety and/or the additional O- and N-atoms in the 1- and 7-positions.
