Non-peptidic inhibitors of human leukocyte elastase. 4. Design, synthesis, and in vitro and in vivo activity of a series of .beta.-carbolinone-containing trifluoromethyl ketones
作者:Chris A. Veale、James R. Jr. Damewood、Gary B. Steelman、Craig Bryant、Bruce Gomes、Joseph Williams
DOI:10.1021/jm00001a014
日期:1995.1
A novel series of humanleukocyteelastase (HLE) inhibitors containing the beta-carbolinone ring system are reported. The design of these trifluoromethyl ketone-based inhibitors used a combination of structural information obtained from X-ray crystallography and molecular modeling investigations. The beta-carbolinone ring in these compounds serves as a highly efficient peptidiomimetic for the P2-P3
The synthesis of deuterium-labeled N-nitrosodiethanolamine and N-nitroso-2-hydroxymorpholine
作者:Richard N. Loeppky、Heping Xiong
DOI:10.1002/jlcr.2580341114
日期:1994.11
Two deuterated derivatives of N-nitrosodiethanolamine and two deuterated derivatives of N-Nitroso-2-hydroxymorpholine were prepared. 1,1,1′,1′-2H4-N-Nitrosodiethanolamine 1a was prepared in 99% isotopic purity by simple base catalyzed H-D exchange. 2,2,2′,2′-2H4-N-Nitrosodiethanolamine 1b was synthesized in 98% isotopic purity by the LiAlD4 reduction of dimethyl iminodiethanoate, followed by acid catalyzed nitrosation. 5,5-2H2-N-Nitroso-2-hydroxymorpholine 2a was prepared in 99% isotopic purity through a series of steps involving 1) the selective base catalyzed H-D exchange of the CH2 adjacent to the ester function of 2,2-diethoxyethylcarboethoxymethylnitrosamine, 2) its reduction with diisobutylaluminum hydride at −8°C followed by 3) acid catalyzed hydrolysis of the acetal and cyclization to the hemiacetal. 2-2H-N-Nitroso-2-hydroxymorpholine 2b (98% isotopic purity) was prepared through the LiAlD4 reduction of 2-hydroxyethylcorboethoxymethylnitrosamine at −78°C.
Synthesis of Optically Active <b><i>C</i></b>-Allylglycine Derivatives and Conversion into Isoquinolones
作者:Udo Nubbemeyer、Nong Zhang
DOI:10.1055/s-2002-19804
日期:——
synthesized via an auxiliary controlled diastereoselective aza-Claisen rearrangement. The stereodirecting unit is placed on an auxiliary derived from commercially available (S)-proline. After N-allylation. the obtained optically active allylamines were reacted with various N-protected glycyl fluorides to give the (2R)-C-allylglycyl amides in good yields. The diastereoselectivity of the asymmetric allylation
This invention relates to tricyclic compounds having spiro union represented by the following formula (I) or its salt which is useful as a drug, and in particular, as an inhibitor for activated blood coagulation factor X, which can be administered orally and which exhibits strong anticoagulation action.
1
The invention also relates to a pharmacophore which was derived from the compound and is useful in molecular designing of the FXa inhibitor.
Synthesis of 15-azayohimban, a new heterocyclic ring system
作者:Nativitat Vails、Víctor M. Segarra、Maillo Luisa C、Joan Bosch
DOI:10.1016/s0040-4020(01)80944-3
日期:1991.1
Two synthetic routes to the 15-azayohimban ringsystem have been studied. The first one, based on a Pictet-Spengler condensation between tryptamine and piperidine acetal 4, gave very low yields of pentacycles 2a. The second, more efficient route involves as the crucial step a cyclization of a N-acyliminium cation generated from imide 11. The different course of the Pictet-Spengler reaction from amino