145013-05-4Relevant articles and documents
Preparation of N,N'-bis-tert-butoxycarbonylthiourea
Iwanowicz,Poss,Lin
, p. 1443 - 1445 (1993)
The preparation of N,N'-bis-tert-butoxycarbonylthiourea from thiourea and di-tert-butyl dicarbonate in tetrahydrofuran is described.
Di-aryl guanidinium derivatives: Towards improved α2-Adrenergic affinity and antagonist activity
McMullan, Michela,Kelly, Brendan,Mihigo, Helene B.,Keogh, Aaron P.,Rodriguez, Fernando,Brocos-Mosquera, Iria,García-Bea, Aintzane,Miranda-Azpiazu, Patricia,Callado, Luis F.,Rozas, Isabel
supporting information, (2020/11/05)
Compounds with excellent receptor engagement displaying α2-AR antagonist activity are useful not only for therapeutic purposes (e.g. antidepressants), but also to help in the crystallization of this particular GPCR. Therefore, based on our broad experience in the topic, we have prepared eighteen di-aryl (phenyl and/or pyridin-2-yl) mono- or di-substituted guanidines and 2-aminoimidazolines. The in vitro α2-AR binding affinity experiments in human brain tissue showed the advantage of a 2-aminoimidazolinium cation, a di-arylmethylene core, a conformationally locked pyridin-2-yl-guanidine and a di-substituted guanidinium to achieve good α2-AR engagement. After different in vitro [35S]GTPγS binding experiments in human prefrontal cortex tissue, it was possible to identify that compounds 7a, 7b and 7c were α2-AR partial agonist, whereas 8h was a potent α2-AR antagonist. Docking and MD studies with a model of α2A-AR and two crystal structures suggest that antagonism is achieved by compounds carrying a di-substituted guanidine which substituent occupy a pocket adjacent to TM5 without engaging S2005.42 or S2045.46, and a mono-substituted cationic group, which favorably interacts with E942.65.
α-Amino Acid-Isosteric α-Amino Tetrazoles
Zhao, Ting,Kurpiewska, Katarzyna,Kalinowska-T?us?cik, Justyna,Herdtweck, Eberhardt,D?mling, Alexander
supporting information, p. 3009 - 3018 (2016/03/26)
The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field.
INHIBITORS OF BETA-SECRETASE
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Paragraph 0182; 0183, (2014/03/24)
The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.