Metabolites of orally active NO-independent pyrazolopyridine stimulators of soluble guanylate cyclase.
The pyrazolopyridine stimulators of soluble guanylate cyclase BAY 41-2272 and 41-8543 were oxidised in rats and dogs at their 5-pyrimidinyl-cyclopropyl and -morpholino residue. These metabolites activate the soluble guanylate cyclase, induce vasoelaxation and thereby may contribute to the in vivo activity of BAY 41-2272 and BAY 41-8543.
Straub
Alexander
A
Institute of Medicinal Chemistry, Pharma Research Centre, Bayer AG, D-42096, Wuppertal, Germany. alexander.straub.as@bayer-ag.de
Benet-Buckholz
Jordi
J
Fröde
Rita
R
Kern
Armin
A
Kohlsdorfer
Christian
C
Schmitt
Peter
P
Schwarz
Thomas
T
Siefert
Hans Martin
HM
Stasch
Johannes Peter
JP
D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D018360:Crystallography, X-Ray; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D009025:Morpholines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014664:Vasodilation / Q000187:drug effects
C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; C450679:BAY 41-8543; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; C118531:pyrazolopyridine; D009569:Nitric Oxide; D006162:Guanylate Cyclase