| Identification | More | [Name]
Losartan potassium | [CAS]
124750-99-8 | [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
MK 954
1h-imidazole-5-methanol,2-butyl-4-chloro-1-((2’-(1h-tetrazol-5-yl)(1,1’-biphe
2-butyl-4-chloro-1-(2’-(tetrazol-5-yl)biphenyl-4-ylmethyl)-1h-imidazole-5-me
dupont753
l-158086
mk-0954
thanolpotassium
2-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol,monopotassium salt
MK-95
LOSARTANPOTASSIUM(SUBJECTTOPATENTFREE)
2-Butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-
Aradois | [EINECS(EC#)]
200-287-4 | [Molecular Formula]
C22H23ClKN6O | [MDL Number]
MFCD02092704 | [Molecular Weight]
462.01 | [MOL File]
124750-99-8.mol |
| Chemical Properties | Back Directory | [Appearance]
White to Off-White Crystalline Powder | [Melting point ]
263-265°C | [storage temp. ]
Inert atmosphere,Room Temperature | [solubility ]
Freely soluble in water and in methanol, slightly soluble in acetonitrile. | [form ]
powder or crystals | [color ]
Off-white | [Usage]
A nonpeptide angiotensin II AT1-receptor antagonist | [Merck ]
14,5583 | [BRN ]
5845770 | [BCS Class]
1 | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months. | [InChI]
InChI=1S/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;/h4-7,9-12,30H,2-3,8,13-14H2,1H3;/q-1;+1 | [InChIKey]
OXCMYAYHXIHQOA-UHFFFAOYSA-N | [SMILES]
C1(C=CC=CC=1C1=CC=C(CN2C(CO)=C(Cl)N=C2CCCC)C=C1)C1=NN=NN1[K] | [CAS DataBase Reference]
124750-99-8(CAS DataBase Reference) |
| Safety Data | Back Directory | [Hazard Codes ]
Xi | [Risk Statements ]
R36/37/38:Irritating to eyes, respiratory system and skin . | [Safety Statements ]
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice .
S36/37/39:Wear suitable protective clothing, gloves and eye/face protection . | [WGK Germany ]
3 | [RTECS ]
NI6755100 | [HS Code ]
2933290000 | [Hazardous Substances Data]
124750-99-8(Hazardous Substances Data) |
| Questions And Answer | Back Directory | [Description]
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. | [References]
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
|
| Hazard Information | Back Directory | [Chemical Properties]
White to Off-White Crystalline Powder | [Originator]
DuPont Merck (U.S.A.) | [Uses]
A nonpeptide angiotensin II AT1-receptor antagonist. Antihypertensive. | [Uses]
antihypertensive, AT1 angiotensin II antagonist | [Uses]
Coronary vasodilator used in the diagnosis of coronary heart disease (adenosine A2A agonist). | [Manufacturing Process]
2-Butyl-4-chloro-1-(2'-(tetrazol-5-yl)biphenyl-4-ylmethyl)-1H-imidazole-5- methanolpotassium was synthesized in 5 stages.
1. Methyl 4'-methylbiphenyl-2-carboxylate (44.2 mmol), 0.5 N KOH in methanol (133 mmol), and water (50 mL) were mixed and refluxed under nitrogen. After 5 hours, the solvent was removed in vacuo and water (200 mL) and ethyl acetate (200 mL) added. The aqueous layer was acidified with concentrated hydrochloric acid to a pH of 3 and the layers were separated. The aqueous phase was extracted with ethyl acetate, the organic layers collected, dried (MgSO4) and the solvent removed in vacuo to yield 8.71 g of a 4'-methylbiphenyl-2-carboxylic acid, melting point 140.0-145.0°C.
2. 4'-Methylbiphenyl-2-carboxylic acid (41 mmol) and thionyl chloride (411 mmol) were mixed and refluxed for 2 hours. The excess thionyl chloride was removed in vacuo and the residue was taken up in toluene. The toluene was removed by rotary evaporation. The crude acid chloride was then added slowly to cold (0°C) concentrated NH4OH (50 mL) so that the temperature was kept below 15°C. After 15 minutes of stirring, water (100 mL) was added and solids precipitated. These were collected, washed with water and dried under high vacuum over P2O5 to yield 7.45 g of a white solid, melting point 126.0-128.5°C. The above product amide (35 mmol) and thionyl chloride (353 mmol) were mixed and refluxed for 3 hours. The thionyl chloride was removed using the same procedure as described above. The residue was washed with a little hexane to yield 6.64 g of 4'-methyl-2-cyanobiphenyl, melting point 44.0- 47.0°C.
3. 4'-Methyl-2-cyanobiphenyl (5.59 g) was brominated using benzoyl peroxide as an initiator. The product was recrystallized from ether to yield 4.7 g of 4'- bromomethyl-2-cyanobiphenyl, melting point 114.5-120.0°C.
4. 4'-Bromomethyl-2-cyanobiphenyl (4.6 g) was alkylated onto 2-n-butyl-4-
chloro-5-(hydroxymethyl)-imidazole. For separation of the product was used a
flash chromatography in 1:1 hexane/ethyl acetate over silica gel. The
regioisomeric products yielded 2.53 g of the faster eluting isomer.
Recrystallization from acetonitrile yielded 1.57 g of analytically pure 2-n-butyl4-chloro-1-[2'-cyanobiphenyl-4-yl)methyl]-5-(hydroxymethyl)-imidazole,
melting point 153.5 -155.5°C.
5. 2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)-methyl]-5-(hydroxymethyl)-
imidazole (10 mmole), sodium azide (10 mmol), and ammonium chloride (30
mmol) were mixed in DMF (150 mL) under N2 at 100°C for 2 days, after
which the temperature was raised to 120°C for 6 days. The reaction was
cooled and 3 more equivalents each of ammonium chloride and sodium azide
were added. The reaction was again heated for 5 days at 120°C. The reaction
was cooled, the inorganic salts filtered, and the filtrate solvent removed in
vacuo. Water (200 mL) and ethyl acetate (200 mL) were added to the residue
and the layers were separated. The aqueous layer was extracted with ethyl
acetate, the organic layers were collected, dried (MgSO4) and the solvent
removed in vacuo, to yield a dark yellow oil. The product was purified by flash
chromatography in 100% ethyl acetate to 100% ethanol over silica gel to
yield 5.60 g of a light yellow 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1Htetrazol-5-yl)biphenyl-4-yl)methyl]imidazole. Recrystallization from acetonitrile
yielded 4.36 g of light yellow crystals which still melted broadly. The crystals
were taken up in 100 mL of hot acetonitrile. The solid that did not dissolve
was filtered off to yield 1.04 g of product as a light yellow solid, melting point
of 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-
yl)methyl]imidazole 183.5-184.5°C.
2-n-Butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-
yl)methyl]imidazole may be converted to potassium salt. | [Brand name]
Cozaar (Merck). | [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. | [storage]
Store at -20°C |
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