- Axially chiral Ni(II) complexes of α-amino acids: Separation of enantiomers and kinetics of racemization
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Herein we present design, synthesis, chiral HPLC resolution, and kinetics of racemization of axially chiral Ni(II) complexes of glycine and di-(benzyl)glycine Schiff bases. We found that while the ortho-fluoro derivatives are configurationally unstable, t
- Zhang, Wenzhong,Ekomo, Romuald Eto,Roussel, Christian,Moriwaki, Hiroki,Abe, Hidenori,Han, Jianlin,Soloshonok, Vadim A.
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- Improved and scalable methods for the synthesis of midazolam drug and its analogues using isocyanide reagents
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Abstract: In this research, two improved and scalable methods for the synthesis of midazolam and its analogues have been described. Midazolam has been synthesized using isocyanide reagents in satisfactory yield. In this methodology, imidazobenzodiazepine intermediates can be easily prepared via an improved process. One-pot condensation of benzodiazepines with mono-anion of tosylmethyl isocyanide or ethyl isocyanoacetate under mild condition led to formation of imidazobenzodiazepine. In the first method, tosylmethyl isocyanide (Tos-MIC) is used and the number of synthetic steps are decreased in comparison to previous report. In the second method, ethyl isocyanoacetate which is commonly used for the synthesis of some imidazobenzodiazepines, is consumed to generate midazolam. The latter, a relatively different method for the synthesis of midazolam analogues has been reported. Graphical abstract: [Figure not available: see fulltext.].
- Taghizadeh, Mohammad Javad,malakpouri, Gholam reza,Javidan, Abdollah
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p. 785 - 794
(2019/03/27)
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- Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists
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Since its discovery in 1988 by Yanagisawa et al., endothelin (ET), a potent vasoconstrictor, has been widely implicated in the pathophysiology of cardiovascular, cerebrovascular, and renal diseases. Many research groups have embarked on the discovery and development of ET receptor antagonists for the treatment of such diseases. While several compounds, e.g., ambrisentan 2, are in late clinical trials for various indications, one compound (bosentan, Tracleer) is being marketed to treat pulmonary arterial hypertension. Inspired by the structure of ambrisentan 2, we designed a novel class of ET receptor antagonists based on a 1,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-one scaffold. Here, we report on the preparation as well as the in vitro and in vivo structure-activity relationships of these derivatives. Potent dual ET A/ETB receptor antagonists with affinities in the low nanomolar range have been identified. In addition, several compounds efficiently reduced arterial blood pressure after oral administration to Dahl salt sensitive rats. In this animal model, the efficacy of the benzo[e] [1,4]diazepin-2-one derivative rac-39au was superior to that of racemic ambrisentan, rac-2.
- Bolli, Martin H.,Marfurt, Judith,Grisostomi, Corinna,Boss, Christoph,Binkert, Christoph,Hess, Patrick,Treiber, Alexander,Thorin, Eric,Morrison, Keith,Buchmann, Stephan,Bur, Daniel,Ramuz, Henri,Clozel, Martine,Fischli, Walter,Weller, Thomas
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p. 2776 - 2795
(2007/10/03)
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- Synthesis and spectral properties of 2-[(o- and p-substituted)aminophenyl]-3H-5-[(o- and p-substituted)phenyl]-7-chloro-1,4-benzodiazepines
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A series of twelve new 2-[(o- and p-substituted)aminophenyl]-3H-5-[(o- and p-substituted)phenyl]-7-chloro-1,4-benzodiazepines, which have possible pharmacological properties has been obtained. The synthesis was carried out following six steps. The structure of all products was corroborated by ir, 1H nmr, 13C nmr and ms. In addition for the compound 2-(o-chloroaminophenyl)-3H-5-(o-fluorophenyl)-7-chloro-1,4-benzodiazepine 7, its structure was confirmed by X-ray diffraction.
- Cortes Cortes,Salazar Franco,Garcia Mellado
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p. 663 - 669
(2007/10/03)
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