Spiro(imidazo[1,2-a]pyrano[2,3-c]pyridine-9-indenes) as inhibitors of gastric acid secretion.
Asymmetric and symmetric spiro(imidazo[1,2-a]pyrano[2,3-c]pyridine-9-indenes) were prepared using a synthetic approach that comprised a cross-metathesis reaction and an acid-catalyzed cycloisomerisation as key steps. The target compounds constitute potent inhibitors of the gastric proton pump enzyme with inhibitory activity comparable to potassium-competitive acid blockers (P-CABs) belonging to the known 9-aryl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine series. Spiro(imidazo[1,2-a]pyrano[2,3-c]pyridine-9,2'-indenes) represent the first example for P-CABs, in which the distance between the heterocyclic scaffold and the aryl residue has been modified, and are promising candidates for further development as anti-ulcer drugs.
Palmer
Andreas Marc
AM
NYCOMED GmbH, Byk-Gulden-Str. 2, D-78467 Konstanz, Germany. andreas.palmer@nycomed.com
Chrismann
Sandra
S
Münch
Gabriela
G
Brehm
Christof
C
Zimmermann
Peter Jan
PJ
Buhr
Wilm
W
Senn-Bilfinger
Jörg
J
Feth
Martin Philipp
MP
Simon
Wolfgang Alexander
WA
D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007192:Indenes / Q000138:chemical synthesis / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D007093:Imidazoles; D007192:Indenes; D054328:Proton Pump Inhibitors; D013141:Spiro Compounds