5105-78-2Relevant articles and documents
Total Synthesis of the 7,10-Epimer of the Proposed Structure of Amphidinolide N, Part I: Synthesis of the C1-C13 Subunit
Ochiai, Koji,Kuppusamy, Sankar,Yasui, Yusuke,Okano, Tsubasa,Matsumoto, Yasunobu,Gupta, Nishant R.,Takahashi, Yohei,Kubota, Takaaki,Kobayashi, Jun'ichi,Hayashi, Yujiro
, p. 3282 - 3286 (2016)
Amphidinolide N, the structure of which has been recently revised, is a 26-membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10-epimer of the proposed structure of amphidinolide N, we have synthesized the C1-C13 subunit enantio- and diastereoselectively. Key reactions include an l-proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao-Fleming oxidation. To aid late-stage manipulations, we also developed the 4-(N-benzyloxycarbonyl-N-methylamino)butyryl group as a novel ester protective group for the C9 alcohol.
Abolishing Dopamine D2long/D3Receptor Affinity of Subtype-Selective Carbamoylguanidine-Type Histamine H2Receptor Agonists
Tropmann, Katharina,Bresinsky, Merlin,Forster, Lisa,M?nnich, Denise,Buschauer, Armin,Wittmann, Hans-Joachim,Hübner, Harald,Gmeiner, Peter,Pockes, Steffen,Strasser, Andrea
supporting information, p. 8684 - 8709 (2021/06/30)
3-(2-Amino-4-methylthiazol-5-yl)propyl-substituted carbamoylguanidines are potent, subtype-selective histamine H2receptor (H2R) agonists, but their applicability as pharmacological tools to elucidate the largely unknown H2R functions in the central nervous system (CNS) is compromised by their concomitant high affinity toward dopamine D2-like receptors (especially to the D3R). To improve the selectivity, a series of novel carbamoylguanidine-type ligands containing various heterocycles, spacers, and side residues were rationally designed, synthesized, and tested in binding and/or functional assays at H1-4and D2long/3receptors. This study revealed a couple of selective candidates (among others31and47), and the most promising ones were screened at several off-target receptors, showing good selectivities. Docking studies suggest that the amino acid residues (3.28, 3.32, E2.49, E2.51, 5.42, and 7.35) are responsible for the different affinities at the H2- and D2long/3-receptors. These results provide a solid base for the exploration of the H2R functions in the brain in further studies.
CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES
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Page/Page column 133; 136; 161, (2020/01/31)
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
