Chapter 19 Agents for the Treatment of Peptic Ulcer Disease

Bauer, R. F.; Collins, Paul W.; Jones, Peter H.

doi:10.1016/s0065-7743(08)61167-7

Cited by 7 publications

(3 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20). The activity of compounds depends on the nature of both the "Het" and "Y" groups [185]. In the 1990s, a small series of compounds was reported with 2-, 3-or 4-pyridyl as Het group and a derivative of 2-cyano-1,1-iminodiamine or 2-nitro-1,1-ethenediamine as Y group; in these compounds the terminal nitrogen of Y was incorporated into a 1,4-dihydropyridine ring [186,187].…”

Section: 4-dhps As H 2 -Histamine Receptor Antagonistsmentioning

confidence: 99%

1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives (Part 1): Action in Ion Channels and GPCRs

Ioan¹,

Carosati²,

Micucci³

et al. 2011

CMC

View full text Add to dashboard Cite

Since the pioneering studies of Fleckenstein and co-workers, L-Type Calcium Channel (LTCC) blockers have attracted large interest due to their effectiveness in treating several cardiovascular diseases. Medicinal chemists achieved high potency and tissue selectivity by decorating the 1-4-DHP nucleus, the most studied scaffold among LTCC blockers. Nowadays it is clear that the 1,4-DHP nucleus is a privileged scaffold since, when appropriately substituted, it can selectively modulate diverse receptors, channels and enzymes. Therefore, the 1,4-DHP scaffold could be used to treat various diseases by a single-ligand multi-target approach. In this review, we describe the structure-activity relationships of 1,4-DHPs at ion channels, G-protein coupled receptors, and outline the potential for future therapeutic applications.

show abstract

Section: 4-dhps As H 2 -Histamine Receptor Antagonistsmentioning

confidence: 99%

1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives (Part 1): Action in Ion Channels and GPCRs

Ioan¹,

Carosati²,

Micucci³

et al. 2011

CMC

View full text Add to dashboard Cite

show abstract

“…These have included a search for more useful H2-receptor antagonists for the treatment of peptic ulcer with gastric hyper acidity (5)(6)(7). A H2-receptor antagonist with the imidazole group in its structure, cimeti dine, was the first drug to be used for the clini cal treatment of ulcer patients.…”

Section: Abstract 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-mentioning

confidence: 99%

“…Since then, H2-receptor antagonists, ranitidine (8) and famotidine (9), which do not have the imida zole group in their structure have been used, and a series of diaminothiadiazole oxide and dioxides (10,11) have been reported. Recent ly, new H2-receptor antagonists, L-643,441, lamtidine (AH 22216), loxitidine (AH 23844) and BMY-25368 (SK&F 94482), which contain a piperidinomethylphenyl moiety in their structure have been reported (6,7,12). These compounds produced unsurmountable antago nism in guinea pig atria and showed very po tent and long lasting inhibition of gastric acid secretion.…”

Section: Abstract 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-mentioning

confidence: 99%

Time-Dependent Interaction of a New H2-Receptor Antagonist, IT-066, with the Receptor in the Atria of Guinea Pig

Muramatsu

Hirose-Kijima

Aihara

et al. 1991

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

3-Amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-butenylamino] 3-cyclobutene-1,2-dione hydrochloride (IT-066) showed a highly potent and long last ing H2-receptor blocking action in guinea pig atria. The inhibitory effect of IT-066 on the histamine-induced positive chronotropic response increased concentration and time-dependently. A short period of treatment with IT-066 shifted the concentration response curve of histamine to the right in parallel, without decreasing the maximal response to histamine. With prolongation of the treatment, the concentration-response curve shifted further to the right with time-dependent suppression of the maximal re sponse to histamine. The inhibitory effect of IT-066 was irreversible. The dissociation constant for histamine (KA) was not changed by prolongation of the time of incuba tion with IT-066. The dissociation constant for IT-066 (KB) was decreased with the prolongation of the treatment. Kinetic analysis of the time-dependent inhibition showed a two-step reaction: the first was reversible and the second was irreversible. Preincubation of the atria with ranitidine, however, protected the H2-receptor from the apparently irreversible antagonism of IT-066. These results suggest that IT-066 has a time-dependent and irreversible interaction with the H2-receptor and that the in teraction may be responsible for the potent and long lasting H2-receptor blocking ac tion of IT-066.The discovery of burimamide, a prototype H2-receptor antagonist (1), has prompted in tensive investigations to clarify the physiologi cal and pharmacological involvement of his tamine in the regulation of gastric acid secre tion (2-4). These have included a search for more useful H2-receptor antagonists for the treatment of peptic ulcer with gastric hyper acidity (5-7). A H2-receptor antagonist with the imidazole group in its structure, cimeti dine, was the first drug to be used for the clini cal treatment of ulcer patients. Since then, H2-receptor antagonists, ranitidine (8) and famotidine (9), which do not have the imida zole group in their structure have been used, and a series of diaminothiadiazole oxide and dioxides (10, 11) have been reported. Recent ly, new H2-receptor antagonists, L-643,441, lamtidine (AH 22216), loxitidine (AH 23844) and BMY-25368 (SK&F 94482), which contain a piperidinomethylphenyl moiety in their structure have been reported (6,7,12). These compounds produced unsurmountable antago nism in guinea pig atria and showed very po tent and long lasting inhibition of gastric acid secretion. The mechanism, however, has not

show abstract