Losartan potassium CAS 124750-99-8
Introduction：Basic information about Losartan potassium CAS 124750-99-8, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Losartan potassium Basic informationDescription References Background
| 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;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 |
| CAS: | 124750-99-8 |
| MF: | C22H23ClKN6O |
| MW: | 462.01 |
| EINECS: | 200-287-4 |
| Product Categories: | API;Cardiovascular APIs;Aromatics;Heterocycles;API Reference Standard;COZAAR;APIS;Hypertension;Intermediates & Fine Chemicals;Pharmaceuticals;Losartan;124750-99-8 |
| Mol File: | 124750-99-8.mol |
Losartan potassium Chemical Properties
| 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 |
| Water Solubility | H2O: 2mg/mL, clear |
| 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 Information
| Hazard Codes | Xi |
| Risk Statements | 36/37/38 |
| Safety Statements | 26-36/37/39 |
| WGK Germany | 3 |
| RTECS | NI6755100 |
| HS Code | 2933290000 |
| Storage Class | 11 - Combustible Solids |
| 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 |
| Description | 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- |
| Description | 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 oralantihypertensive. It is efficacious and long lasting in controlling blood pressure inspontaneous hypertensive rats, in patients with essential hypertension in addition tothose patients with renal impairment. Since losartan functions by competitiveantagonism at the level of receptor, which represents the most direct way ofselectively inhibiting the renin-angiotensin system (RAS) independent of the sourceof AT II, its use has been reported to be free of the coughing side effect exhibited bythe ACE inhibitors. In contrast to calcium channel blockers, losartan does notappear to cause ankle edema, headache and tachycardia. It is also reported to be inclinical trials for the treatment of heart failure. Other reports indicate that losartanmay have potential efficacy as an anxiolytic, an antiglaucoma agent, in addition to in providing protection against stroke and in preventing the myointimal proliferativeresponse of the vascular wall after coronary angioplasty and surgery. |
| 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 aflash chromatography in 1:1 hexane/ethyl acetate over silica gel. Theregioisomeric 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 (30mmol) were mixed in DMF (150 mL) under N2 at 100°C for 2 days, afterwhich the temperature was raised to 120°C for 6 days. The reaction wascooled and 3 more equivalents each of ammonium chloride and sodium azidewere added. The reaction was again heated for 5 days at 120°C. The reactionwas cooled, the inorganic salts filtered, and the filtrate solvent removed invacuo. Water (200 mL) and ethyl acetate (200 mL) were added to the residueand the layers were separated. The aqueous layer was extracted with ethylacetate, the organic layers were collected, dried (MgSO4) and the solventremoved in vacuo, to yield a dark yellow oil. The product was purified by flashchromatography in 100% ethyl acetate to 100% ethanol over silica gel toyield 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 acetonitrileyielded 4.36 g of light yellow crystals which still melted broadly. The crystalswere taken up in 100 mL of hot acetonitrile. The solid that did not dissolvewas filtered off to yield 1.04 g of product as a light yellow solid, melting pointof 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. |
| storage | RT (desiccate) |
| Background | Losartan is a known angiotensin II receptor antagonist by selectively and competitively blocking the binding of the angiotensin II hormone. In clinical settings, it is useful as an antihypertensive agent and also displays neuroprotective effects against chronic fatigue stress. Losartan inhibits collagen I synthesis and induces sirtuin 1 expression and activity. |
| References | [1] [2] A T CHIU. Nonpeptide angiotensin II receptor antagonists. VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent.[J]. Journal of Pharmacology and Experimental Therapeutics, 1990, 252 2: 711-718. [3] M. MCINTYRE . Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of its efficacy and safety in essential hypertension[J]. Pharmacology & Therapeutics, 1997, 74 2: Pages 181-194. DOI:10.1016/s0163-7258(97)82002-5 [4] BENJAMIN DIOP-FRIMPONG. Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108 7: 2909-2914. DOI:10.1073/pnas.1018892108 [5] EIRINI PANTAZI. Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation.[J]. World Journal of Gastroenterology, 2015, 21 26: 8021-8031. DOI:10.3748/wjg.v21.i26.8021 [6] ANIL KUMAR. Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress.[J]. Inflammopharmacology, 2015, 23 6: 291-305. DOI:10.1007/s10787-015-0238-z [7] J. L. MIGUEL-CARRASCO. Mechanisms underlying the cardiac antifibrotic effects of losartan metabolites[J]. Scientific Reports, 2017. DOI:10.1038/srep41865 |
Losartan potassium Preparation Products And Raw materials
| Raw materials | Thionyl chloride-->4′-Methylbiphenyl-2-carboxylic acid methyl ester-->2-n-Butyl-4-Chloro-5-Hydroxymethyl Imidazole-->Potassium hydroxide-->Sodium azide-->Ammonium hydroxide-->Des[2'-(1H-tetrazol-5-yl)] 2-Cyanolosartan Carboxaldehyde-->Losartan-->2-Butyl-4-chloro-5-formylimidazole-->4’-[(2-butyl-4-chloro-5-hydroxymethyl)-1H-imidazol-1-yl)methyl]-[1,1’-Biphenyl]-2-carbonitrile-->4-Bromomethyl-2-cyanobiphenyl |
| Preparation Products | N-Trityl Losartan Carboxylic Acid |
