HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Losartan
LOS · dup89 · LOSARTAN · Compound 89 · Losartan（base） · Losartan (DUP 89) · nyl)-4-yl)methyl)- · Losartan (DuP-753)
Identifikatoren & physikalische Daten
| CAS No. | 114798-26-4 |
|---|---|
| Summenformel | C22H23ClN6O |
| Durchschnittliche Molmasse | 422,9 g/mol |
| Monoisotopische Masse | 422,16218704 g/mol |
| SMILES | CCCCc1nc(Cl)c(CO)n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1 |
| InChIKey | PSIFNNKUMBGKDQ-UHFFFAOYSA-N |
| PubChem CID | 3961 |
| ChEMBL | CHEMBL191 |
| ChEBI | CHEBI:6541 |
| EC No. | 601-329-8 |
| DTXSID | DTXSID7023227 |
Chemische & physikalische Eigenschaften
| XLogP | 4,3 |
|---|---|
| Polarare Oberfläche (TPSA) | 92,5 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 5 |
| Frei drehbare Bindungen | 8 |
| Schwere Atome | 30 |
| Formalladung | 0 |
| Komplexität | 520 |
| Arzneimittel | Pharmaceuticals -> Used in SwitzerlandPharmaceuticals -> AntihypertensivesPharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | 6.12.53 |
| Color/Form | Light yellow solid |
| Löslichkeit | <1mg/mL4.70e-03 g/LDMSO (Slightly), Methanol (Slightly)4.8mg/L at 20℃ |
| Human Drugs | Breast FeedingLactationMilk, HumanAntihypertensive AgentsAngiotensin II Type 1 Receptor BlockersPharmaceuticalsAntihypertensive medicines |
| Decomposition | Hazardous decomposition products: Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas, potassium oxides. |
| Schmelzpunkt | 178-184183.5-184.5 °C183.5 - 184.5 °C183-184 C |
| Physical Description | Solid |
| Stability/Shelf Life | Stable under recommended storage conditions. |
| Dissociation Constants | 5.5pKa: 5-6 |
| Collision Cross Section | 201.6 Ų [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: APCI+Dataset: TOXCASTSource Identifier: DTXSID3044209]200.3 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]199.2 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]197.63 Ų [M+H]+ [CCS Type: TW200.49 Ų [M+H]+ |
| Other Experimental Properties | White to off-white free-flowing crystalline powder. Freely soluble in watersoluble in alcoholsslightly soluble in common organic solvents, such as acetonitrile, methyl ethyl ketone /Losartan monopotassium salt/ |
| Siedepunkt | 682.0±65.0 °C(Predicted) |
| Dichte | 1.35±0.1 g/cm3(Predicted) |
| Dampfdruck | 0.002Pa at 20℃ |
| Lagerbedingungen | under inert gas (nitrogen or Argon) at 2-8°C |
| Aggregatzustand | Solid |
| pKa (Säurekonstante) | 5-6(at 25℃) |
| Farbe | White to Off-White |
| InChI | 1S/C22H23ClN6O/c1-2-3-8-20-24-21(23)19(14-30)29(20)13-15-9-11-16(12-10-15)17-6-4-5-7-18(17)22-25-27-28-26-22/h4-7,9-12,30H,2-3,8,13-14H2,1H3,(H,25,26,27,28) |
| InChIKey | PSIFNNKUMBGKDQ-UHFFFAOYSA-N |
| SMILES | OCC1=C(Cl)N=C(CCCC)N1CC2=CC=C(C3=C(C4=NNN=N4)C=CC=C3)C=C2 |
| LogP (Verteilungskoeffizient) | 1.1 at 20℃ |
| CAS Datenbank | 114798-26-4(CAS DataBase Reference) |
| EPA chemische Informationen | 1H-Imidazole-5-methanol, 2-butyl-4-chloro-1-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]- (114798-26-4) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH315 (48.1%): Causes skin irritation [Warning Skin corrosion/irritation]P203, P260, P261, P263, P264, P264+P265, P270, P271, P272, P273, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 81 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 29-04-2013 https://echa.europa.eu/registration-dossier/-/registered-dossier/7457 |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including losartan potassium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Losartan potassium/ |
| Hazard Classes and Categories | Skin Irrit. 2 (48.1%) |
| Firefighting Hazards | Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), potassium oxides. |
| Brandbekämpfungsverfahren | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. |
| Lagerbedingungen | Store at 25 °C (77 °F)excursions permitted to 15-30 °C (59-86 °F). Keep container tightly closed. Protect from light.Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Store under inert gas. Moisture sensitive. |
| Reinigungsverfahren | Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapours, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.Waste treatment methods: Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product. |
| Preventive Measures | Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.Appropriate engineering controls: General industrial hygiene practice.Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker. |
| Personal Protective Equipment (PPE) | Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
| Wechselwirkungen | ... This study was undertaken to evaluate how the chronic administration of deoxycortisone acetate (DOCA) modifies the effects of losartan on BP, renal injury, and other variables in /N(G)-nitro-L-arginine methyl ester (L-NAME)/ hypertensive rats. The following groups were used: Control, DOCA, L-NAME, L-NAME + losartan, L-NAME + DOCA, and L-NAME + DOCA + losartan. Tail systolic BP was measured twice a week. After 4-wk evolution, mean arterial pressure and metabolic, morphologic, and renal variables were measured. The final mean arterial pressure values were 116 +/- 6 mm Hg for control, 107 +/- 2 mmHg for DOCA, 151 +/- 5 mmHg for L-NAME, 123 +/- 2 mmHg for L-NAME + losartan, 170 +/- 3 mm Hg for L-NAME + DOCA, and 171 +/- 5.5 mmHg for L-NAME + DOCA + losartan. Losartan prevented microalbuminuria, hyaline arteriopathy, and glomerulosclerosis of L-NAME hypertension but was ineffective in L-NAME + DOCA-treated rats. ... Plasma renin activity was suppressed in the DOCA (0.55 +/- 0.2) and L-NAME + DOCA (0.60 +/- 10.2) groups but unsuppressed in the L-NAME + DOCA + losartan group (5.8 +/- 1). The conclusion is that DOCA blocks the preventive effect of losartan on the increased BP and renal injury of L-NAME hypertension ... These data also suggest that losartan prevents L-NAME hypertension by blocking the activity of systemic Ang II. /Salt not specified/NSAIDs are known to attenuate the effects of some antihypertensive medications ... A multicenter study assessing the effect of indomethacin on the antihypertensive effects of losartan and captopril /was conducted/. After 4 weeks of placebo washout, hypertensive patients received 6 weeks of active antihypertensive therapy with ... 50 mg losartan once daily (n=111) ... This was followed by 1 week of concomitant therapy with indomethacin (75 mg daily). The primary outcome measure was the change in mean 24-hour ambulatory diastolic blood pressure after the addition of indomethacin. ... Losartan significantly lowered ambulatory diastolic blood pressure (losartan -5.3 mm Hg, P:<0.001 ...) after 6 weeks of therapy. Indomethacin significantly attenuated the 24-hour ambulatory diastolic blood pressure for ... losartan (2.2 mm Hg, P:<0.05) ... Changes in daytime diastolic blood pressure (7:00 AM to 11:00 PM) were similar to the 24-hour response in both groups. Nighttime diastolic blood pressure (11:01 PM to 6:59 AM) ... with losartan was unaffected (0.4 mm Hg). Thus, concurrent treatment with indomethacin similarly attenuates the 24-hour antihypertensive response to losartan ... /Salt not specified/Potential pharmacologic interaction (attenuated hypotensive effects) when angiotensin II receptor antagonists are used concomitantly with nonsteroidal anti-inflammatory agents (NSAIAs), including selective cyclooxygenase-2 (COX-2) inhibitors. Possible deterioration of renal function in geriatric, volume-depleted (including those receiving concomitant diuretic therapy), or renally impaired patientsrenal function should be monitored periodically in patients receiving concomitant therapy with losartan and an NSAIA, including selective COX-2 inhibitors.Decreased plasma concentrations of losartan and its active metabolite observed when losartan potassium is used concomitantly with rifampin.For more Interactions (Complete) data for Losartan (20 total), please visit the HSDB record page. |
| Hepatotoxicity | Losartan has been associated with a low rate of serum aminotransferase elevations ( |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.4X10+5(SRC), determined from a structure estimation method(2), indicates that losartan is expected to be immobile in soil(SRC). The pKa of losartan is 5.05(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of losartan from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.3X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Losartan is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-18 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2014).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.4X10+5(SRC), determined from a structure estimation method(2), indicates that losartan is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.3X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 110(SRC), from an estimated log Kow of 4.01(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Biodegradation data in water were not available(SRC, 2014).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), losartan, which has an estimated vapor pressure of 5.4X10-18 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase losartan may be removed from the air by wet and dry deposition(SRC). Losartan contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| Unerwünschte Wirkungen | The primary adverse effects of losartan, including hyperkalemia, renal insufficiency, and angioedema, are reported. |
| Milk Concentrations | EXPERIMENTAL: It is not known whether losartan is excreted in human milk, but significant levels of losartan and its active metabolite were shown to be present in rat milk. |
| Toxizitätsübersicht | IDENTIFICATION AND USE: Losartan is a light yellow solid that is formulated into oral tablets. Losartan is an angiotensin II type 1 (AT1) receptor antagonist. It is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. It is also used to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy and for the treatment of diabetic nephropathy in patients with type 2 diabetes and a history of hypertension. HUMAN EXPOSURE AND TOXICITY: The most likely manifestations of losartan overdose include hypotension and tachycardiabradycardia could be encountered if parasympathetic (vagal) stimulation occurs. The use of lorsartan during pregnancy is contraindicated. While use during the first trimester does not suggest a risk of major anomalies, use during the second and third trimester may cause teratogenicity and severe fetal and neonatal toxicity. Fetal toxic effects may include anuria, oligohydramnios, fetal hypocalvaria, intrauterine growth restriction, premature birth, and patent ductus arteriosus. Anuria-associated oligohydramnios may produce fetal limb contractures, craniofacial deformation, and pulmonary hypoplasia. Severe anuria and hypotension that is resistant to both pressor agents and volume expansion may occur in the newborn following in utero exposure to losartan. ANIMAL STUDIES: Losartan potassium was not carcinogenic when administered at maximally tolerated dosages to rats and mice. Female rats given losartan had a slightly higher incidence of pancreatic acinar adenoma. Also, fertility and reproductive performance were not affected in studies with male rats given oral doses of losartan. The administration of toxic dosage levels in females was associated with a significant decrease in the number of corpora lutea/female, implants/female, and live fetuses/female at C-section. The relationship of these findings to drug-treatment is uncertain since there was no effect at these dosage levels on implants/pregnant female, percent post-implantation loss, or live animals/litter at parturition. Losartan has been shown to produce adverse effects in rat fetuses and neonates, including decreased body weight, delayed physical and behavioral development, mortality and renal toxicity. With the exception of neonatal weight gain doses associated with these effects exceeded 25 mg/kg. These findings are attributed to drug exposure in late gestation and during lactation. Losartan was negative in the microbial mutagenesis and V-79 mammalian cell mutagenesis assays and in the in vitro alkaline elution assay and in vitro and in vivo chromosomal aberration assays. In addition, the active metabolite showed no evidence of genotoxicity in the microbial mutagenesis, in vitro alkaline elution assay, and in vitro chromosomal aberration assays.In a recent case report, a female patient aged 34 with a medical history of asthma, hypertension, and chronic respiratory failure had an overdose of losartan. She intentionally ingested 30 tablets of 25 mg of losartan in a suicide attempt. Illicit substance use was ruled out through a negative urine drug screen. During her hospitalization, the patient developed acute kidney injury and hyperkalemia. Based on the patient's complaint of diffuse abdominal pain, elevated lipase levels (161 U/L), and computed tomography (CT) imaging findings, acute pancreatitis was diagnosed. Supportive care, including fluid resuscitation, pain management, and continuous monitoring of laboratory parameters, was provided, gradually improving her condition. The healthcare team should be mindful of the possibility of drug-induced acute pancreatitis following an overdose of losartan from acute kidney injury and hyperkalemia. |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of losartan can be estimated to be 1.4X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that losartan is expected to be immobile in soil. The pKa of losartan is 5.50(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ In this preliminary, single-dose, open-label, cross-over study conducted in 12 healthy volunteers, psychomotor assessment was carried out by four tests: Simple reaction time (SRT), multiple choice reaction time test (MCRT), critical flicker fusion frequency threshold test (CFFT), and tracking performance test (TPT). Each volunteer received a single dose of each of the three test drugs with a washout period of 10 days between different test sessions and then evaluated for post-drug scores at 2-hr intervals up to 12 hr and then at 24 hr. The changes from the baseline scores by the test drug were statistically analyzed. All the three antihypertensive drugs caused significant improvement in a similar fashion on SRT, MCRT calculated as error index, CFFT, and TPT. Aliskiren caused numerically more improvement than the other two test drugs, suggesting better cognitive profile. However, inter-drug comparisons were nonsignificant. The results of the study highlight improvement of the cognitive functions equally by ramipril, losartan, and aliskiren. The results of the study could be of immense clinical utility in ambulatory hypertensive patients especially engaged in sensory-motor coordination tasks like driving and operating on mechanical tools./SIGNS AND SYMPTOMS/ Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardiabradycardia could occur from parasympathetic (vagal) stimulation./CASE REPORTS/ The fetotoxic effects of angiotensin converting enzyme inhibitors when used during the second half of pregnancy are well known. The more recently developed angiotensin II receptor antagonists appear to yield similar fetal abnormalities. We report a premature infant born to a 41-year-old mother with a long history of infertility who had received losartan therapy for hypertension throughout an undetected pregnancy. Ultrasound examination 2 days prior to delivery identified a single fetus at 29 weeks gestation, anhydramnios, and an empty fetal bladder. The neonatal course was complicated by oliguria, hyperkalemia, marked renal dysfunction, respiratory failure, joint contractures, and a large anterior fontanelle with widely separated sutures. Hypotension (mean arterial pressure <25 torr) on day 1 responded to volume expansion, dopamine, and hydrocortisone. Serum creatinine reached a maximum of 2.7 mg/dL on day 6 and decreased to 0.4 by day 56. No formal urinalysis was performed, but the urine was reported to be visually clear throughout the course. Although a renal ultrasound on day 2 was normal, a follow-up study at 7 months revealed bilateral generalized parenchymal echogenicity, consistent with medical renal disease. Since then, weight and length have been at the 5th percentile or less, with apparent renal tubular acidosis necessitating the addition of sodium citrate supplements. .../CASE REPORTS/ A case of losartan-induced azotemia in a 46-yr-old male diabetic recipient of a kidney transplant who received treatment with 50-100 mg/day of losartan for unsatisfactory blood pressure control is reported. The patient was first on enalapril, but was changed to losartan when renal function deteriorated. On losartan, the patient also had increased serum creatinine concentration and renal insufficiency.For more Human Toxicity Excerpts (Complete) data for Losartan (12 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Losartan's production and use as an antihypertensive(1) may result in its release to the environment through various waste streams(SRC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)losartanDILI PositiveOralDOI:10.1016/j.drudis.2019.09.022 |
| Environmental Bioconcentration | An estimated BCF of 110 was calculated in fish for losartan(SRC), using an estimated log Kow of 4.01(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC). |
| Volatilization from Water/Soil | The Henry's Law constant for losartan is estimated as 3.3X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that losartan is expected to be essentially nonvolatile from water and moist soil surfaces(2). Losartan is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-18 mm Hg(SRC), determined from a fragment constant method(3). |
| Wassergefährdungsklasse (WGK) | WGK 3 |
| R-Sätze (R) | 36/37/38 |
| Gefahrensymbole | Xi |
| Sicherheitshinweise (S) | 26-36 |
| Lagerklasse | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Gefahrstoffdaten | 114798-26-4(Hazardous Substances Data) |
| Gefahrenklasse | Lact.Repr. 1BSkin Sens. 1 |
Anwendungen & Verwendung
Verwenden
Losartan is a nonpeptide angiotensin II AT1-receptor antagonist. Antihypertensive.