168017-85-4

Upstream product

• 168017-83-2 Acetic acid 3-[3-((R)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-ureido]-benzyl ester 
• 153825-72-0 1-(3-Hydroxymethyl-phenyl)-3-((R)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-urea 
• 2949-22-6 Glycine ethyl ester isocyanate 

Downstream Products

• 168017-89-8 {3-[3-((R)-1-Methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-ureido]-benzyloxycarbonylamino}-acetic acid 

Relevant academic research and scientific papers

Synthesis and biological evaluation of a new reversely linked type of dual histamine H2 and gastrin receptor antagonist

In an attempt to improve the low oral absorbability of previously reported dual histamine H2 and gastrin receptor antagonists, compounds of a different type were synthesized and evaluated for biological activity. These new compounds bear a histamine H2 receptor antagonist (H2A) pharmacophore moiety attached to a gastrin receptor antagonist (GA) pharmacophore moiety in a reversed manner, namely the head-to-head manner, different from the previously reported head-to-tail manner. These new hybrid compounds were classified into three types: type 1, the regular amide type bearing a roxatidine moiety; type II, the reversed amide type bearing a roxatidine moiety: and type III, hybrid compounds bearing a famotidine moiety directly connected to a GA moiety without a spacer. Among them, only (R)-1-[3-(N'- {4-[2-(N-aminosulfonylamidino)ethylthiomethyl]thiazol-2- yl}guanidinomethyl)phenyl]-3(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4- benzodiazepin-3-yl)urea (42), belonging to type III, shorted a weak but distinct histamine H2 receptor-antagonistic activity as well as a modest gastrin receptor-antagonistic activity. Of most importance was the finding that this compound showed a weak but clearly improved in vivo oral antigastric acid secretory activity as a result of the structural changes, including the decreased molecular weight.

Synthesis and pharmacological evaluation of highly potent dual histamine H2 and gastrin receptor antagonists

The chemical modification of the dual histamine H2 and gastrin receptor antagonists described in our preceding paper, particularly the modification of spacers as well as the alteration of their connecting bonds at the gastrin receptor antagonist site (GA) from the amide bond to the carbamate bond, significantly improved not only their dual activity but also the GA versus CCK-A receptor selectivity.