Preparation of tetrahydroimidazo[2,1-a]isoquinolines and their use as inhibitors of gastric acid secretion.
A series of novel tetrahydroimidazo[2,1-a]isoquinolines was prepared based on a hetero Diels-Alder reaction between an enamine and 1,2,4-triazine as key step. A structure-activity relationship was established focussing on the influence of the substitution pattern in position 3 and 6 of the heterocycle on antisecretory activity, lipophilicity, and pK(a) value. Potent inhibitors of the gastric acid pump were identified.
Palmer
Andreas Marc
AM
NYCOMED GmbH, Byk-Gulden-Str. 2, D-78467 Konstanz, Germany.
Grobbel
Burkhard
B
Brehm
Christof
C
Zimmermann
Peter Jan
PJ
Buhr
Wilm
W
Feth
Martin Philipp
MP
Holst
Hans Christof
HC
Simon
Wolfgang Alexander
WA
D004353:Drug Evaluation, Preclinical; D005744:Gastric Acid / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000187:drug effects; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry
D005765:Gastrointestinal Agents; D007093:Imidazoles; D007546:Isoquinolines; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D014227:Triazines; C117197:imidazolone; C093444:1,2,4-triazine