22190-35-8Relevant articles and documents
Fast and Efficient Nickel(II)-catalysed Transfer Hydrogenation of Quinolines with Ammonia Borane
Vermaak, Vincent,Vosloo, Hermanus C. M.,Swarts, Andrew J.
supporting information, p. 5788 - 5793 (2020/12/01)
Herein we report the first Ni(II)-catalysed transfer hydrogenation of quinolines using ammonia borane (AB) as hydrogen (H2) source. An in situ generated Ni(II)-bis(pyrazolyl)pyridine pre-catalyst could hydrogenate quinoline and its derivatives in excellent yields of up to 90% at 25 °C in 30 minutes. Spectroscopic studies revealed that a Ni(II)-hydride is responsible for the transfer hydrogenation of quinoline to 1,2,3,4-tetrahydroquinoline via a 1,4-dihydroquinoline intermediate. (Figure presented.).
Design, structure-activity relationship, and pharmacokinetic profile of pyrazole-based indoline factor Xa inhibitors
Varnes, Jeffrey G.,Wacker, Dean A.,Jacobson, Irina C.,Quan, Mimi L.,Ellis, Christopher D.,Rossi, Karen A.,He, Ming Y.,Luettgen, Joseph M.,Knabb, Robert M.,Bai, Steven,He, Kan,Lam, Patrick Y.S.,Wexler, Ruth R.
, p. 6481 - 6488 (2008/03/18)
A new series of pyrazole-based factor Xa inhibitors have been identified as part of our ongoing efforts to optimize previously reported clinical candidate razaxaban. Concern over the possible formation of primary aniline metabolites via amide hydrolysis led to the replacement of the primary amide linker between the pyrazole and phenyl moieties with secondary amides. This was accomplished by replacing the aniline with a variety of heterobicycles, of which indolines were the most potent. The indoline series demonstrated subnanomolar factor Xa binding Kis, modest to high selectivity versus other serine proteases, and good in vitro clotting activity. A small number of indoline fXa inhibitors were profiled in a dog pharmacokinetic model, one of which demonstrated pharmacokinetic parameters similar to that of clinical candidate razaxaban.
Nitrogen containing heterobicycles as factor Xa inhibitors
-
, (2008/06/13)
This invention relates generally to nitrogen containing heterobicycles of formulas A and B: which are inhibitors of trypsin-like serine protease enzymes, especially factor Xa, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.