Discovery of Novel Tetrahydroisoquinoline Derivatives as Potent and Selective Factor Xa Inhibitors.

Abstract

A series of 17 novel tetrahydroisoquinoline derivatives, e.g. (I), is prepared. Among these derivatives, the 4-pyridinyl derivative (Ie) as well as its mesylate salt possess the most promising anti-FXa activity. Importantly, the derivatives not containing a carboxylate group at the piperidine ring show high acute toxicity. -(UENO, H.; YOKOTA, K.; HOSHI, J.-I.; YASUE, K.; HAYASHI, M.; UCHIDA, I.; AISAKA, K.; HASE, Y.; KATOH, S.; CHO*, H.; Bioorg. Med. Chem. Lett. 15 (2005) 1, 185-189; Cent. Pharm. Res. Inst., Japan Tobacco Inc., Takatsuki, Osaka 569, Japan; Eng.) -Mischke 18-136

Imaging of parastomal hernia using three-dimensional intrastomal ultrasonography (Br J Surg 2011: 98: 1026–1029)

“…Benzimidazoles are a class of privileged core structures that are found in a broad spectrum of biologically active compounds such as nonpeptide luteinizing hormone‐releasing hormone (LHRH) antagonist,1 lymphocyte specific kinase (Lck) inhibitor,2 N ‐methyl‐ D ‐aspartate (NMDA) antagonist,3 neuropeptide Y Y1 receptor antagonist,4 nonpeptide thrombin inhibitor,5 5‐lipoxygenase inhibitor,6 factor Xa (FXa) inhibitor,7 and poly(ADP‐ribose)polymerase (PRAP) inhibitor 8. Benzimidazoles have also been widely used in fungicides, herbicides, and other veterinary application 9.…”

Synthesis and evaluation of novel 2,4-diaminopyrimidines bearing bicyclic aminobenzazepines for anaplastic lymphoma kinase (ALK) inhibitor

“…Nitrobenzazepinone 7 was prepared by nitration with KNO 3 from benzazepinone 6, which was synthesized from the corresponding 1-tetralone by applying Schmidt reaction with NaN 3 /HCl. [22] Reduction of amide group in compound 7 by treatment of BH 3 /THF provided benzoazepine 8, which was treated with trifluoroacetic anhydride (TFAA) to afford compound 9.…”

Synthesis, characterization, and antimicrobial activities of clubbed [1,2,4]‐oxadiazoles with fluorobenzimidazoles

“…So by this idea in view, synthesis of fluorobenzimidazole is the interesting area of research. Interest in benzimidazole containing structure stems not only because of exhibiting broad spectrum of pharmacological activity [3] but also displaying significant activities against several viruses such as casein kinase 2 [4], factor Xa [5], hepatitis C virus [6].…”