128972-02-1Relevant articles and documents
5-(HETEROCYCLYLALKANOYL)AMINO-4-HYDROXYPENTANAMIDES
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, (2008/06/13)
This invention concerns novel nitrogen derivatives of the formula I STR1 (and their pharmaceutically-acceptable salts), together with pharmaceutical compositions containing them. The nitrogen derivatives are inhibitors of the catalytic action of renin. Th
1,2,4-Triazolopyrazine Derivatives with Human Renin Inhibitory Activity. 1. Synthesis and Biological Properties of Alkyl Alcohol and Statine Derivatives
Roberts, David A.,Bradbury, Robert H.,Brown, David,Faull, Alan,Griffiths, David,et al.
, p. 2326 - 2334 (2007/10/02)
A series of 1,2,4-triazolopyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) transition-state mimetics, have been prepared.Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-pyrazin-3-yl>-3-(3-pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen.Compounds 12m, 12o, and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration.On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion.The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.
AN EFFICIENT SYNTHESIS OF 3-ALKYL-5-ARYL-2(1H)-PYRAZINONES
Bradbury, Robert H.,Griffiths, David,Rivett, Janet E.
, p. 1647 - 1653 (2007/10/02)
The preparation of several 3-alkyl-5-aryl-2(1H)-pyrazinones is described.The regiochemical outcome of the condensation reaction between amine acid amides and phenylglyoxal is discussed and alternative, more efficient route is reported, involving ring-clos
