86604-74-2Relevant articles and documents
Diversified synthesis of novel quinoline and dibenzo thiazepine derivatives using known active intermediates
Sharada,Satyanarayana Reddy,Sammaiah,Sumalatha
, p. 7959 - 7966 (2013/09/23)
The novel drug development to control resisting infections in conventional drug therapy is a need of today. Few antiulcer relative derivatives developed by approaching convergent synthesis. The derivatives synthesized successfully are dibenzo thiazepine-pyridine (SLN11-SLN15) and benzimidazole-hydroquinoline based derivatives (SLN16-SLN20). It involved the coupling through microwave, sonication and conventional techniques at final step. The efficient technology identified as sonication technique basically time and yield. The reported compounds were structural characterized by elemental analysis and spectral studies such as 1H, 13C NMR and MS.
Identification and synthesis of potential impurities of rabeprazole sodium
Pingili, R. Reddy,Jambula, M. Reddy,Ganta, M. Reddy,Ghanta, M. Reddy,Sajja,Sundaram,Boluggdu, V. Bhaskar
, p. 814 - 818 (2007/10/03)
Rabeprazole sodium (1, Achiphex) is a gastric proton pump inhibitor. It causes dose-dependent inhibition of acid secretion and is useful as an anti-ulcer agent. In the process for the preparation of 1, two potential unknown impurities were identified in HPLC at levels ranging from 0.05-0.8%. Based on mass spectral data vide LC-MS, the two impurities were characterized as 2-{[(4-chloro-3-methyl-2-pyridinyl) methyl] sulfinyl}-1H-bezimidazole (2, chloro analogue of rabeprazole) and 2-[{(4-methoxy-3-methyl-2-pyridinyl)methyl} sulfinyl]-1H-benzimidazole (3, methoxy analogue of rabeprazole). The structures were unambiguously established by independently synthesizing them and co-injecting in HPLC. To our knowledge, the compounds 2 and 3 have not been reported as process impurities elsewhere.
Structure-activity relationship of omeprazole and analogues as Helicobacter pylori urease inhibitors
Kuhler,Fryklund,Bergman,Weilitz,Lee,Larsson
, p. 4906 - 4916 (2007/10/03)
Helicobacter pylori urease belongs to a family of highly conserved urea- hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K+-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K+- ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pK(a)-value of the pyridine, the pK(a)-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of β- mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 μmol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 μmol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.
(H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate
Kohl,Sturm,Senn-Bilfinger,Simon,Kruger,Schaefer,Rainer,Figala,Klemm
, p. 1049 - 1057 (2007/10/02)
[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to undergo the acid-catalyzed transformation is dependent on the nucleophilic/electrophilic properties of the functional groups involved in the formation of 2 since this step is both rate-determining and pH-dependent. The aim of this study was to identify compounds with high (H+,K+)-ATPase inhibitory activity in stimulated gastric glands possessing acidic pH, but low reactivity (high chemical stability) at neutral pH as reflected by in vitro (Na+,K+)-ATPase inhibitory activity. The critical influence of substituents flanking the pyridine 4-methoxy substituent present in all derivatives was carefully studied. The introduction of a 3-methoxy group gave inhibitors possessing a combination of high potency, similar to omeprazole and lansoprazole, but increased stability. As a result of these studies, compound 1a (INN pantoprazole) was selected as a candidate drug and is currently undergoing phase III clinical studies.
[1,3]-Dioxolo[4,5-f]benzimidazoles and [1,4]-dioxino[2,3-f]benzimidazoles
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, (2008/06/13)
Tricyclic ethers of the general formula I STR1 wherein R represents a bond and R1 represents a 1-2C-alkylene radical which is completely or partly substituted by fluorine, or a chlorotrifluoroethylene radical, or R and R1 each represent a difluoromethylene radical, R2 represents hydrogen or a 1-3C-alkyl radical, R3 represents hydrogen or a 1-3C-alkyl or 1-3C-alkoxy radical, R4 represents hydrogen or a 1-3C-alkyl radical and n represents the number 0 or 1, and their salts are new compounds with a marked protective effect on the stomach.
