title: Metabolites of orally active NO-independent pyrazolopyridine stimulators of soluble guanylate cyclase.
abstract: 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.
authors.affiliation: Institute of Medicinal Chemistry, Pharma Research Centre, Bayer AG, D-42096, Wuppertal, Germany. alexander.straub.as@bayer-ag.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Straub
authors.forename: Jordi
authors.initials: J
authors.lastname: Benet-Buckholz
authors.forename: Rita
authors.initials: R
authors.lastname: Fröde
authors.forename: Armin
authors.initials: A
authors.lastname: Kern
authors.forename: Christian
authors.initials: C
authors.lastname: Kohlsdorfer
authors.forename: Peter
authors.initials: P
authors.lastname: Schmitt
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
authors.forename: Hans Martin
authors.initials: HM
authors.lastname: Siefert
authors.forename: Johannes Peter
authors.initials: JP
authors.lastname: Stasch
mesh_terms: 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
chemical_list: 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