124750-99-8

Basic information

• Product Name: Losartan potassium
• Synonyms: 2-BUTYL-4-CHLORO-1-[[2'-(1H-TETRAZOL-5YL)[1,1'-BIPHENYL]-4-YL]METHYL]-1H-IMIDAZOLE-5-METHANOL;2-butyl-4-chloro-1-[[2'-(1h-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1h-imidazole-5-methanol monopotassium salt;2-BUTYL-4-CHLORO-1-[[2'-(1H-TETRAZOLE-5-YL)[1,1'-BIPHENYL]-4-YL]METHYL]-1H-IMIDAZOLE-5-METHANOL, POTASSIUM SALT;COZAAR;DUP 753;LOSARTAN MONOPOTASSIUM SALT;LOSARTAN POTASSIUM;LOSARTAN POTASSIUM SALT
• CAS NO: 124750-99-8
• Molecular Formula: C₂₂H₂₂ClN₆O*K
• Molecular Weight: 462.01
• EINECS: 200-287-4
• Product Categories: Hypertension;Intermediates & Fine Chemicals;Pharmaceuticals;Losartan;APIS;Aromatics;Heterocycles;API Reference Standard;COZAAR;Cardiovascular APIs;API
• Mol File: 124750-99-8.mol
• Article Data: 40

Chemical Properties

• Melting Point: 263-265°C
• Boiling Point: 682 °C at 760mmHg
• Flash Point: 366.3 °C
• Appearance: white to off-white crystalline powder
• Density: 0.986g/mLat 25°C(lit.)
• Vapor Pressure: 1.55E-19mmHg at 25°C
• Storage Temp.: Desiccate at RT
• Solubility: Freely soluble in water and in methanol, slightly soluble in acetonitrile.
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
• Merck: 14,5583
• BRN: 5845770
• CAS DataBase Reference: Losartan potassium(CAS DataBase Reference)
• NIST Chemistry Reference: Losartan potassium(124750-99-8)
• EPA Substance Registry System: Losartan potassium(124750-99-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• WGK Germany: 3
• RTECS: NI6755100
• Hazardous Substances Data: 124750-99-8(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 124750-99-8 differently. You can refer to the following data:
1. As a angiotensin II receptor antagonist, Losartan Potassium is the potassium salt of losartan with antihypertensive activity, which is mainly used in the therapy of high blood pressure (hypertension) and diabetic nephropathy. It functions by relaxing blood vessels so that blood can flow more easily. It is also effective to help protect the kidneys from damage caused by diabetes and lower the risks of stroke in patients suffering from hypertension and myocardial enlargement. Besides, recent study has suggested that losartan is beneficial to reverse age related dysfunction in maintaining normal blood pressure and cellular energy usage on mitochondria and it can probably be used to treat left ventricular hypertrophy. It may also be used as an alternative agent for the treatment of systolic dysfunction, myocardial infarction, coronary artery disease, and heart failure.
2. Angiotensin II is a hormone that plays an important role in regulating blood pressure. Elevated levels of angiotensin II are implicated in inducing and maintaining hypertension, and also in the development of atherosclerosis. Both of these effects are mediated by the angiotensin II type 1 (AT1) receptor. Losartan is an AT1 receptor antagonist with a Ki value of 5-20 nM. It has an attenuating effect on vein graft atherosclerosis in rabbits and effectively reduces arterial blood pressure in rats. In humans, losartan controls hypertension while protecting renal function.
3. Losartan potassium is the first potent and selective non-peptide angiotensin II (AT II) AT1 receptor antagonist introduced to the market as a once-daily oral antihypertensive. It is efficacious and long lasting in controlling blood pressure in spontaneous hypertensive rats, in patients with essential hypertension in addition to those patients with renal impairment. Since losartan functions by competitive antagonism at the level of receptor, which represents the most direct way of selectively inhibiting the renin-angiotensin system (RAS) independent of the source of AT II, its use has been reported to be free of the coughing side effect exhibited by the ACE inhibitors. In contrast to calcium channel blockers, losartan does not appear to cause ankle edema, headache and tachycardia. It is also reported to be in clinical trials for the treatment of heart failure. Other reports indicate that losartan may have potential efficacy as an anxiolytic, an antiglaucoma agent, in addition to in providing protection against stroke and in preventing the myointimal proliferative response of the vascular wall after coronary angioplasty and surgery.

References

Different sources of media describe the References of 124750-99-8 differently. You can refer to the following data:
1. https://en.wikipedia.org/wiki/Losartan https://www.drugbank.ca/drugs/DB00678 https://pubchem.ncbi.nlm.nih.gov/compound/11751549#section=Top http://www.medicinenet.com/losartan-oral/article.htm
2. 1) Merck 14:5583 2) Chiu et al. (1990), Nonpeptide angiotensin II receptor antagonists. VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent; J. Pharmacol. Exp. Ther., 252 711 3) McIntyre et al. (1997), Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of it’s efficacy and safety in essential hypertension; Pharmacol. Ther., 74 181 4) Diop-Frimpong et al. (2011), Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors; Proc. Natl. Acad. Sci. USA, 108 2909 5) Pantazi et al. (2015), Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation; World J. Gastroenterol., 21 8021 6) Kumar et al. (2015), Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress; Inflammopharmacology, 23 291 7) Miguel-Carrasco et al. (2017), Mechanisms underlying the cardiac antifibrotic effects of losartan metabolites; Sci. Rep. 7 41865

Chemical Properties

White to Off-White Crystalline Powder

Originator

DuPont Merck (U.S.A.)

Uses

Different sources of media describe the Uses of 124750-99-8 differently. You can refer to the following data:
1. A nonpeptide angiotensin II AT1-receptor antagonist. Antihypertensive.
2. antihypertensive, AT1 angiotensin II antagonist
3. Coronary vasodilator used in the diagnosis of coronary heart disease (adenosine A2A agonist).

Therapeutic Function

Antihypertensive

Biological Activity

Selective non-peptide angiotensin AT 1 receptor antagonist. Inhibits the contractile effects of angiotensin II on rabbit aorta and jugular vein (pA 2 = 8.27). Orally active antihypertensive agent.

Clinical Use

#N/A

Drug interactions

Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: antagonism of hypotensive effect and increased risk of renal impairment with NSAIDs; hyperkalaemia with ketorolac and other NSAIDs. Antihypertensives: increased risk of hyperkalaemia, hypotension and renal impairment with ACE-Is and aliskiren. Ciclosporin: increased risk of hyperkalaemia and nephrotoxicity. Diuretics: enhanced hypotensive effect; hyperkalaemia with potassium-sparing diuretics. ESAs: increased risk of hyperkalaemia; antagonism of hypotensive effect. Lithium: reduced excretion (possibility of enhanced lithium toxicity). Potassium salts: increased risk of hyperkalaemia. Tacrolimus: increased risk of hyperkalaemia and nephrotoxicity.

InChI:InChI=1/C22H22ClN6O.K/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;/h4-7,9-12H,2-3,8,13-14H2,1H3,(H,25,26,27,28);/q-1;+1

Synthetic route

lorsartan (114798-26-4) → losartan potassium (124750-99-8)

Conditions	Yield
With potassium hydroxide In methanol; isopropyl alcohol at 20℃; for 0.5h;	90%
With potassium hydroxide In methanol for 4h; Heating / reflux;	33%
With potassium hydroxide In methanol for 1h; pH=9; Reflux;

2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)methyl]imidazole-5-carboxaldehyde (124750-67-0) → losartan potassium (124750-99-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate / methanol; N,N-dimethyl acetamide / 1 h / 5 - 20 °C 2.1: sodium azide; triethylamine hydrochloride / N,N-dimethyl acetamide / 16 h / 120 °C 2.2: 80 °C / pH 4.0 3.1: potassium hydroxide / methanol; isopropyl alcohol / 0.5 h / 20 °C View Scheme

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → losartan potassium (124750-99-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl acetamide / 5 h / 20 °C 2.1: sodium tetrahydroborate / methanol; N,N-dimethyl acetamide / 1 h / 5 - 20 °C 3.1: sodium azide; triethylamine hydrochloride / N,N-dimethyl acetamide / 16 h / 120 °C 3.2: 80 °C / pH 4.0 4.1: potassium hydroxide / methanol; isopropyl alcohol / 0.5 h / 20 °C View Scheme

4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile (114772-54-2) → losartan potassium (124750-99-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl acetamide / 5 h / 20 °C 2.1: sodium tetrahydroborate / methanol; N,N-dimethyl acetamide / 1 h / 5 - 20 °C 3.1: sodium azide; triethylamine hydrochloride / N,N-dimethyl acetamide / 16 h / 120 °C 3.2: 80 °C / pH 4.0 4.1: potassium hydroxide / methanol; isopropyl alcohol / 0.5 h / 20 °C View Scheme

2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)-methyl]-5-(hydroxymethyl)imidazole (114772-55-3) → losartan potassium (124750-99-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium azide; triethylamine hydrochloride / N,N-dimethyl acetamide / 16 h / 120 °C 1.2: 80 °C / pH 4.0 2.1: potassium hydroxide / methanol; isopropyl alcohol / 0.5 h / 20 °C View Scheme

losartan potassium (124750-99-8) → 2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylic acid (124750-92-1)

Conditions	Yield
Stage #1: losartan potassium With pyridine; potassium permanganate; tetrabutyl-ammonium chloride In water; acetone at 40 - 50℃; for 1h; Stage #2: With hydrogenchloride In water; acetone Product distribution / selectivity;	72%
Stage #1: losartan potassium With potassium hydroxide In water at 2℃; for 2h; Stage #2: With sodium periodate; ruthenium trichloride In water at 4 - 6.5℃; for 19h;

trityl chloride (76-83-5) + losartan potassium (124750-99-8) → 2-Butyl-4-chloro-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol (124751-00-4)

Conditions	Yield
With triethylamine In dichloromethane; water

cis-Pt(ethylenediamine)nitrate-chloride (468724-95-0) + losartan potassium (124750-99-8) → losartan-cisULS

Conditions	Yield
In N,N-dimethyl-formamide at 60℃; for 72h;

losartan potassium (124750-99-8) → 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxylic acid monohydrate (913611-27-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium hydroxide / water / 2 h / 2 °C 1.2: 19 h / 4 - 6.5 °C 2.1: hydrogenchloride / acetic acid 3.1: water / 72 h / centrifuge tube View Scheme

Upstream product

• 124750-67-0 2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)methyl]imidazole-5-carboxaldehyde 
• 114772-54-2 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile 
• 114772-53-1 2-Cyano-4'-methylbiphenyl 
• 114772-55-3 2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)-methyl]-5-(hydroxymethyl)imidazole 
• 155884-01-8 (2-(2H-tetrazol-5-yl)phenyl)boronic acid 
• 151012-31-6 2-n-Butyl-4-chloro-1-(4-bromobenzyl)-1H-imidazole-5-methanol 
• 67-56-1 methanol 
• 124751-00-4 2-Butyl-4-chloro-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol 
• 114798-26-4 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole 
• 133909-99-6 2-n-butyl-4-chloro-1-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-imidazole-5-methanol 
• 114798-26-4 lorsartan 
• 1310-58-3 potassium hydroxide 
• 83857-96-9 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde 

Downstream Products

• 114798-26-4 lorsartan 
• 124751-00-4 2-Butyl-4-chloro-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol 
• 727718-93-6 2-butyl-4-chloro-5-(azidomethyl)-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4yl)methyl]-1H-imidazole 
• 1200445-39-1 1-(((3R,3aR,6R,6aR)-6-(5,6-bis(nitrooxy)hexanoyloxy)hexahydrofuro[3,2-b]furan-3-yloxy)carbonyloxy)ethyl 2-butyl-4-chloro-1-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-imidazole-5-carboxylate 
• 1200445-28-8 1-(((3R,3aR,6R,6aR)-6-(5,6-bis(nitrooxy)hexanoyloxy)hexahydrofuro[3,2-b]furan-3-yloxy)carbonyloxy)ethyl 1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-4-chloro-1H-imidazole-5-carboxylate 
• 1196117-80-2 (3S,3aR,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl 2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylate 
• 1186124-18-4 1-[({[(R)-5-(nitrooxy)hexyl]oxy}carbonyl)oxy]ethyl 2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylate 
• 1186123-58-9 1-[({[(R)-5-(nitrooxy)hexyl]oxy}carbonyl)oxy]ethyl 2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylate 
• 947331-10-4 2-butyl-4-chloro-1-((2'-(2-trityl-2H-tetrazol-5-yl)[biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylic acid 
• 913611-27-5 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxylic acid monohydrate 
• 133909-99-6 2-n-butyl-4-chloro-1-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-imidazole-5-methanol 

Relevant articles and documents

COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE

To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.

NOVEL ZINC AZIDE COMPLEX AND A PROCESS FOR PREPARING TETRAZOLE DERIVATIVES USING THE SAME

The present invention relates to a novel zinc azide complex. The present invention also relates to a process for preparing 5-substituted-1H-tetrazole derivatives from nitrile derivatives by using the zinc azide complex. According to the present invention, in particular, pharmaceutically active compounds for treating hypertension or intermediates useful for preparation thereof can be prepared effectively.

AN IMPROVED PROCESS FOR PREPARING LOSARTAN POTASSIUM

The present invention relates to an improved process for preparing Losartan Potassium of formula (I).