6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole

• ChemBase ID: 222
• Molecular Formular: C17H19N3O3S
• Molecular Mass: 345.41606
• Monoisotopic Mass: 345.11471248
• SMILES: S(=O)(Cc1ncc(c(OC)c1C)C)c1[nH]c2c(n1)ccc(OC)c2
• Canonical SMILES: COc1ccc2c(c1)[nH]c(n2)S(=O)Cc1ncc(c(c1C)OC)C
• InChI: InChI=1S/C17H19N3O3S/c1-10-8-18-15(11(2)16(10)23-4)9-24(21)17-19-13-6-5-12(22-3)7-14(13)20-17/h5-8H,9H2,1-4H3,(H,19,20)
• InChIKey: SUBDBMMJDZJVOS-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole; 5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole
• IUPAC Traditional name: 5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-3H-1,3-benzodiazole; 5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole; antra; omeprazole
• Brand Name: Nexiam; Nexium; Nexium IV; Lucen; Esopral; Axagon; Antra; Audazol; Aulcer; Belmazol; Ceprandal; Danlox; Demeprazol; Desec; Dizprazol; Dudencer; Elgam; Emeproton; Epirazole; Erbolin; Exter; Gasec; Gastrimut; Gastroloc; Gibancer; Indurgan; Inhibitron; Inhipump; Lensor; Logastric; Lomac; Losec; Mepral; Miol; Miracid; Mopral; Morecon; Nilsec; Nopramin; Ocid; Olexin; Omapren; Omebeta 20; Omed; Omegast; Omepral; Omeprazon; Omeprol; Omesek; Omezol; Omezolan; Omid; Omisec; Omizac; Ompanyt; Ortanol; Osiren; Ozoken; Paprazol; Parizac; Pepticum; Pepticus; Peptilcer; Prazentol; Prazidec; Prazolit; Prilosec; Procelac; Proclor; Prysma; Ramezol; Regulacid; Result; Sanamidol; Secrepina; Tedec Ulceral; Ulceral; Ulcesep; Ulcometion; Ulcozol; Ulcsep; Ulsen; Ultop; Ulzol; Victrix; Zefxon; Zegerid; Zepral; Zimor; Zoltum
• Synonyms: Esomeprazole Sodium; Esomperazole; esomeprazole; Esomeprazole; 6-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole; (±)-Omeprazole; Gastrogard; Gastroloc; Mepral; Mopral; Omepral; Zoltum; Audazol; Belmazol; Logastric; Omapren; Omeprazen; Parizac; 5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole; Omeprazol [INN-Spanish]; Omeprazolum [INN-Latin]; OMEP; OMZ; OMP; Omeprazole magnesium; omeprazole; Omeprazole; Prilosec; Zegerid; Prilosec OTC; 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole; Antra; Losec; Omeprazole; 5-methoxy-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazole; 5-methoxy-2-((4-methoxy-3,5-dimethyl-pyridin-2-yl)methylsulfinyl)-3h-benzoimidazole

Database IDs

• CAS Number: 161796-78-7; 73590-58-6; 131959-78-9
• MDL Number: MFCD00002233; MFCD00083192
• PubChem SID: 160963685; 46509065; 24897870
• PubChem CID: 4594

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.294158
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 2.361715
• LogD (pH = 7.4): 2.4276938
• Log P: 2.433509
• Molar Refractivity: 93.6623 cm^3
• Polarizability: 37.349922 Å^3
• Polar Surface Area: 77.1 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.66
• LOG S: -2.98
• Solubility (Water): 3.59e-01 g/l

PROPERTIES

Physical Property

• Solubility: 82.3 mg/L; Acetonitrile; DMSO; DMSO: >19 mg/mL; Ethanol; ethanol: soluble4.5 mg/mL; H2O: soluble0.5 mg/mL; Very slightly soluble in water
• Apperance: white solid; White to Off-White Solid
• Melting Point: 148-150°C (dec.)
• Hydrophobicity(logP): 0.6; 2.565

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: DD9087000
• European Hazard Symbols: Irritant (Xi)
• German water hazard class: 2
• Risk Statements: 36/37/38
• Safety Statements: 26-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H315-H319-H335
• GHS Precautionary statements: P261-P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: adrenergic receptor
• Gene Information: human ... ABCB1(5243), CYP1A2(1544)
• Mechanism of Action: Inhibits gastric acid secretion; Proton pump inhibitor

Product Information

• Purity: 95%; 98%
• Salt Data: Free Base
• Application(s): Antiulcer agent
• Pharmacopeia Traceability: traceable to BP 765; traceable to PhEur O0150000; traceable to USP 1478505
• Empirical Formula (Hill Notation): C17H19N3O3S

DETAILS

DrugBank - DB00338

• Drug Groups: approved; investigational
• Description: A highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers and zollinger-ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in the proton pump of gastric parietal cells. [PubChem]
• Indication: For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastroinetestinal bleeds with NSAID use.
• Pharmacology: Omeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Omeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H^+/K^+ ATPase at the secretory surface of the gastric parietal cell. As a result, it inhibits acid secretion into the gastric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
• Toxicity: Symptoms of overdose include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, and dry mouth.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic.
• Absorption: Absorption is rapid, absolute bioavailability (compared to intravenous administration) is about 30-40% at doses of 20-40 mg.
• Half Life: 0.5-1 hour
• Protein Binding: 95%
• Elimination: Urinary excretion is a primary route of excretion of omeprazole metabolites.
• Clearance: * total body cl=500-600 mL/min [healthy]; * 250 mL/min [Geriatric]; * 70 mL/min [Hepatic Impairment]; * 10 - 62 mL/min/1.73 m2 [Renal Impairment]
• References: Yang YX, Lewis JD, Epstein S, Metz DC: Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

DrugBank - DB00736

• Drug Groups: approved; investigational
• Description: A highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers and zollinger-ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in the proton pump of gastric parietal cells. [PubChem]
• Indication: For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastroinetestinal bleeds with NSAID use.
• Pharmacology: Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H^+/K^+ ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
• Toxicity: Blurred vision, confusion, drowsiness, dry mouth, flushing headache, nausea, rapid heartbeat, sweating
• Affected Organisms: Humans and other mammals
• Biotransformation: Mainly hepatic. Esomeprazole is completely metabolized by the cytochrome P450 system via CYP2C19 and CYP3A4. Metabolism produces inactive hydroxy and desmethyl metabolites, which have no effect on gastric acid secretion. Less than 1% of the parent drug is excreted in urine.
• Absorption: 90%
• Half Life: 1-1.5 hours
• Protein Binding: 97%
• Elimination: Approximately 80% of the administered dose of esomeprazole is excreted as metabolites in urine and the remaining 20% is excreted in feces.
• Distribution: * 16 L [healthy volunteers]
• References: Lind T, Rydberg L, Kyleback A, Jonsson A, Andersson T, Hasselgren G, Holmberg J, Rohss K: Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000 Jul;14(7):861-7. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1389

Research Area: Gastro-oesophageal reflux
Biological Activity:
Omeprazole(Prilosec) is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD), laryngopharyngeal reflux (LPR), and Zollinger-Ellison syndrome. [1]

Sigma Aldrich - O104

Biochem/physiol Actions
Binds covalently to proton pump; inhibits gastric secretion.
Caution
Hygroscopic, photosensitive

Toronto Research Chemicals - O635000

Binds covalently to proton pump. It inhibits gastric secretion. Used as an anttiulcerative.

REFERENCES

• Yang YX, Lewis JD, Epstein S, Metz DC: Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53. Pubmed
• Lind T, Rydberg L, Kyleback A, Jonsson A, Andersson T, Hasselgren G, Holmberg J, Rohss K: Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000 Jul;14(7):861-7. Pubmed
• http://en.wikipedia.org/wiki/Omeprazole
• Muller, P., et al.: Arzneimittel-Forsch., 33, 1685 (1983)
• Wallmark, B., et al.: Biochim. Biophys. Acta., 778, 549 (1983)
• Morii, M., et al.: J. Biol. chem., 268, 21553 (1983)
• Ritter, M., et al.: Br. J. Pharmacol., 124, 627 (1998)
• Eur. Pat., 1979, Aktiebolag Haessle, 5 129; CA, 92, 198396z, (synth, pharmacol)
• Adams, M.H. et al., Clin. Pharm., 1988, 7, 725, (rev)
• Brndstrom, A. et al., Acta Chem. Scand., 1989, 43, 536; 549; 569; 577; 587; 595, (props, bibl)
• Ohishi, H. et al., Acta Cryst. C, 1989, 45, 1921, (cryst struct)
• Maton, P.N., N. Engl. J. Med., 1991, 324, 965, (rev)
• Hetzel, D.J., Digestion, Suppl. 1, 1992, 51, 35, (clin trials, rev)
• Ferner, R.E. et al., Human Exp. Toxicol., 1993, 12, 541, (tox, human)
• Massoomi, F. et al., Pharmacotherapy (Carlisle, Mass.), 1993, 13, 46, (rev)
• Yeomans, N.D., Adverse Drug React. Toxicol. Rev., 1994, 13, 145, (tox, rev)
• Creutzfeldt, W., Drug Saf., 1994, 10, 66, (rev)
• Wilde, M.I. et al., Drugs, 1994, 48, 91, (rev)
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 7th edn., Akademie-Verlag, 1994, 5818, (synonyms)
• Unge, S. et al., Tetrahedron: Asymmetry, 1997, 8, 1967-1970, (bibl, resoln, abs config)
• Langtry, H.D. et al., Drugs, 1998, 56, 447-486, (rev)