13523-86-9

Usage

Uses

Used in Pharmaceutical Industry:
Pindolol is used as an antihypertensive agent for treating arterial hypertension. It helps in managing high blood pressure by blocking the effects of adrenaline on the heart and blood vessels, leading to a decrease in heart rate and blood pressure.
Pindolol is used as an antianginal agent for preventing angina stress attacks. It works by reducing the workload on the heart and improving blood flow to the heart muscles, thus providing relief from chest pain and discomfort.
Pindolol is used as an antiarrhythmic agent for treating supraventricular tachycardia, tachysystolic form of atrial fibrillation, and superventricular extrasystole. It helps in regulating the heart's rhythm and preventing irregular heartbeats.
Pindolol is used as an antiglaucoma agent for managing increased intraocular pressure. It works by reducing the production of aqueous humor in the eye, thus lowering the pressure and preventing damage to the optic nerve.
Additionally, Pindolol is used as a nonselective β-adrenoblocker, similar to nadolol, and possesses antianginal, antihypertensive, and antiarrhythmic actions. It is available under the brand name Visken by Novartis.

Originator

Betadren, Lagap

Manufacturing Process

4-Hydroxyindole is obtained by debenzylation of 4-benzyloxyindole with hydrogen in the presence of a 5% palladium catalyst on aluminium oxide.10.0 g of 4-hydroxyindole and subsequently 7.4 ml of epichlorohydrin are added while stirring in an atmosphere of nitrogen to a solution of 2.73 g of sodium hydroxide in 65 ml of water. Stirring is effected at room temperaturefor a further 15 h, the reaction mixture is extracted 4 times with 50 ml of methylene chloride and the combined organic layers which have been dried over magnesium sulfate are evaporated at reduced pressure. So 3-chloro-1(4-indolyloxy)-2-propanol is obtained.The 3-chloro-1-(4-indolyloxy)-2-propanol is dissolved in 50 ml of toluene and 50 ml of isopropylamine and heated to the boil for 45 h. Evaporation to dryness is effected in a vacuum, the residue is shaken out thrice between ethyl acetate and a 1 N tartaric acid solution and a 5 N sodium hydroxide solution is then added to the combined tartaric acid phases until an alkaline reaction is obtained. The alkaline solution is shaken out thrice with 50 ml of methylene chloride, the extracts are dried over magnesium sulfate and the solvent evaporated in vacuum. The residue is crystallized from ethyl acetate/ether to give the 4-(2-hydroxy-3-isopropylaminopropoxy)indole.

Therapeutic Function

Beta-adrenergic blocker

Biological Activity

5-HT 1A/1B ? receptor antagonist, with roughly equal affinity for each subtype. A partial agonist at mouse and human β 3 -adrenoceptors.

Biochem/physiol Actions

β1-adrenoceptor antagonist; putative 5-HT1A serotonin receptor agonist; vasodilator.

Clinical Use

Beta-blocker: Hypertension Angina

Drug interactions

Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: NSAIDs antagonise hypotensive effect. Anti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone; increased risk of myocardial depression and bradycardia with flecainide. Antidepressants: enhanced hypotensive effect with MAOIs. Antihypertensives; enhanced hypotensive effect; increased risk of withdrawal hypertension with clonidine; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin. Antimalarials: increased risk of bradycardia with mefloquine. Antipsychotics: enhanced hypotensive effect with phenothiazines. Calcium-channel blockers: increased risk of bradycardia and AV block with diltiazem; hypotension and heart failure possible with nifedipine and nisoldipine; asystole, severe hypotension and heart failure with verapamil. Cytotoxics: possible increased risk of bradycardia with crizotinib. Diuretics: enhanced hypotensive effect. Fingolimod: possibly increased risk of bradycardia. Moxisylyte: possible severe postural hypotension. Sympathomimetics: severe hypertension with adrenaline and noradrenaline and possibly with dobutamine.

Metabolic pathway

Several metabolites of pindolol formed in vitro are detected after a 24 h incubation of human hepatocytes in both pure culture and co-culture by adding rat liver epithelial cells. The hepatocytes are able to oxidize the isopropyl amine moiety and the pyrrole ring of the indole moiety and conjugate pindolol as sulfates and glucuronides.

Metabolism

Pindolol (Visken) is extensively absorbed from the gastrointestinal tract. First-pass metabolism is estimated at about 15%, and its plasma half-life is on the order of 3 to 4 hours.The binding of pindolol to plasma proteins is approximately 50%.The metabolic fate of pindolol is not completely understood, although 50% of an administered dose is recovered, primarily in the urine, as unchanged drug.

InChI:InChI=1/C14H20N2O2/c1-10(2)16-8-11(17)9-18-14-5-3-4-13-12(14)6-7-15-13/h3-7,10-11,15-17H,8-9H2,1-2H3/p+1/t11-/m1/s1

Upstream product

• 76989-08-7 1-<1-(4-methylphenyl)sulfonyl-4-indolyloxy>-3-(2-propylamino)-2-propanol 
• 75-31-0 isopropylamine 
• 76989-09-8 1-chloro-3-<1-(4-methylphenyl)sulfonyl-4-indolyloxy>-2-propanol 
• 144024-32-8 4-<1-(4-methylphenyl)sulfonyl-3-pyrrolyl>-4-oxobutanal 
• 96-24-2 3-monochloro-1,2-propanediol 
• 74088-78-1 3-isopropyl-5-(4-indolyloxymethyl)-oxazolidin-2-one 
• 23694-87-3 N-[3-(4-indolyloxy)-2-hydroxypropyl]amine 
• 81745-07-5 5-[2-((E)-2-Dimethylamino-vinyl)-3-nitro-phenoxymethyl]-3-isopropyl-oxazolidin-2-one 
• 74088-75-8 3-isopropyl-5-(2-methyl-3-nitrophenoxymethyl)-oxazolidin-2-one 
• 81132-32-3 <2R>-(+)-1-isopropylamino-3-(2-methyl-3-nitrophenoxy)-2-propanol 
• 81102-68-3 Toluene-4-sulfonic acid (S)-2-hydroxy-3-(2-methyl-3-nitro-phenoxy)-propyl ester 
• 81102-65-0 (S)-2,2-Dimethyl-4-(2-methyl-3-nitro-phenoxymethyl)-[1,3]dioxolane 
• 81102-66-1 <2R>-3-(2-methyl-3-nitrophenoxy)-1,2-propanediol 

Downstream Products

• 26328-11-0 (S)-pindolol 
• 68374-35-6 (+)-Pindolol 
• 2380-94-1 1H-indol-4-ol 

Related news

Effect of single doses of Pindolol (cas 13523-86-9) and d-fenfluramine on flumazenil-induced anxiety in panic disorder patients08/10/2019

The effects of the 5-HT1A receptor blocker pindolol and the 5-HT releasing and uptake blocking agent d-fenfluramine, both used as indirect serotonin agonists, on flumazenil-induced acute anxiety reactions were studied in panic disorder patients to test the hypothesis that serotonin (5-HT) inhibi...detailed

Relevant academic research and scientific papers

Synthetic method of pindolol medicine intermediate (I)-4-(2-hydroxyl-3-isopropyl amino propoxy)indole

The invention relates to a synthetic method of pindolol medicine intermediate (I)-4-(2-hydroxyl-3-isopropyl amino propoxy)indole. The synthetic method comprises the following steps: adding 0.17 mol of 4-Hydroxyindole, 0.18 mol of sodium sulfite and 230 to 260 ml of sodium chloride solution into a reaction vessel with a stirrer and a thermometer, controlling a stirring speed at 110 to 130 rpm, dropwise adding 0.176 to 0.179 mol of (I) epoxy amine propane, then continuously stirring for 16 to 18 h, extracting by virtue of cyclohexane, merging extraction solutions, dehydrating by virtue of phosphorus pentoxide, steaming out a solvent, adding 230 to 260 ml of acetonitrile and 90 to 130 ml of isopropylamine into the remainder, increasing the temperature of the solution to 90 to 95 DEG C, performing the reaction for 26 to 29 h, concentrating and steaming, extracting for 6 to 8 times by virtue of trichloro ethylene, merging the trichloro ethylene layers, adding a sodium hydrogen sulfite solution, adjusting the pH of the solution to 9 to 10, extracting the solution by virtue of methylbenzene, dehydrating by virtue of a dehydrating agent, decompressing and concentrating, adding the remainder into chlorobenzene, increasing the temperature of the solution to 40 to 45 DEG C, concentrating a filtrate, precipitating crystals, and re-crystallizing for 7 to 9 times in the chlorobenzene to obtain (I)-4(2-hydroxyl-3-isopropyl amino propoxy)indole.

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.

THERAPY FOR COMPLICATIONS OF DIABETES

A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.

ANTIHYPERTENSIVE THERAPY

A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.

FLUORESCENCE BASED DETECTION OF SUBSTANCES

A method for the fluorescent detection of a substance, the method comprising providing particles comprising a metal or a metal oxide core, wherein one or more optionally fluorescently tagged antibodies or human specific peptide nucleic acid (PNA) oligomers for binding to a substance is/are bound, directly or indirectly, to the surface of the metal or metal oxide; contacting a substrate, which may or may not have the substance on its surface, with the particles for a time sufficient to allow the antibody/PNA oligomer to bind with the substance; removing those particles which have not bound to the substrate; if the antibodies or PNA oligomers are not fluorescently tagged, contacting the substrate with one or more fluorophores that selectively bind with the antibody and/or substance, then optionally washing the substrate to remove unbound fluorophores; and illuminating the substrate with appropriate radiation to show the fluorophores on the substrate.

Method for treating resistant hypertension

A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.

New, concise route to indoles bearing oxygen or sulfur substituent at the 4-position. Synthesis of (±)- and (S)-(-)-pindolol and (±)-chuangxinmycin

A new method for the synthesis of 4-alkoxy- and 4-[alkyl (or aryl)thio]indoles has been developed by using the indolone 3 as a common intermediate. The indolone 3 was prepared from N-(phenylsulfonyl)pyrrole (7) and the α-chlorosulfide 8 in four steps. Heating of a mixture of 3 and an appropriate alcohol in the presence of p-toluenesulfonic acid and cupric chloride afforded the 4-alkoxyindoles 11a-d. The method was applied to the synthesis of (±)-pindolol (19) and (S)-(-)-pindolol (20). Thiols also reacted with 3 in the presence of boron trifluoride to give 4-[aryl (or alkyl)thio]indoles 12, 21a, b, and 22a-d. The (indol-4-ylthio)acetate 22c was employed as a key intermediate for a concise total synthesis of (±)- chuangxinmycin (27).

Preparation of alkyl-substituted indoles in the benzene portion. Part 8. Improved practical synthesis of 4,4-dialkoxy-1-(1-arylsulfonyl-3-pyrrolyl)-1-butanone and 4-(1-arylsulfonyl-3-pyrrolyl)-4-oxobutanal, and a novel synthetic procedure for 4-alkoxyindole derivatives

Important precursors (1 and 2) for the synthesis of 4-substituted indole derivatives were readily obtained by acid treatment of a tosylamide (13), which was prepared in a single operation by treatment of 10 with N-tosyl-N',N'-dimethylformamidine (TsN=CHNMe2). Compound (10) was effectively synthesized from nitromethane and acrolein by way of a nitro compound (15). A novel indole formation reaction from the tosyl-amide (13) to gain short access to 4-alkoxyindoles, such as 16, 17, 19, and 21 is presented.

Preparation of alkyl-substituted indoles in the benzene portion. Part 7. Synthesis of (±)- and (S)-(-)-pindolol

A new, short-step synthesis of a β-adrenergic blocking agent, pindolol, 1-(4-indolyloxy)-3-(2-propylamino)-2-propanol, is described. The acid-catalyzed indole cyclization reaction of 4-[1-(4-methylphenyl)sulfonyl-3-pyrrolyl]-4-oxobutanal (14) in the presence of (±)-3-chloro-1,2-propanediol (12) and (R)-1-O-[(4-methylphenyl)sulfonyl]glycerol (24) afforded (±)-1-chloro-3-[1-(4-methylphenyl)sulfonyl-4-indolyloxy]-2-propanol (15) and (R)-(-)-3-[1-(4-methylphenyl)sulfonyl-4-indolyloxy]-1-[(4-methylphenyl sulfonyloxy]-2-propanol (25). Reaction of these with isopropylamine and removal of the protecting group at the indole nitrogen gave (±)- and (S)-(-)-pindolol (3 and 4), thus constituting an efficient three-step synthesis of 3 and 4 from the readily available aldehyde (14).

4-hydroxyindole derivatives, the process for preparation thereof and their use

The invention relates to new 4-hydroxyindole derivatives of general formula: STR1 in which R represents a labile protective group and R1 can represent hydrogen, a C1 -C6 alkyl radical, a C3 -C6 cycloalkyl radical, a lower alkoxy radical, a lower hydroxyalkyl radical, a lower (lower alkoxy) alkyl radical, a phenyl radical optionally substituted with a halogen atom or a lower alkyl or lower alkoxy radical, a cyano radical, a radical of formula STR2 in which R2 and R3, which may be identical or different, each represent hydrogen or a lower alkyl radical, R4 represents a hydroxy group, a lower alkyl or lower alkoxy radical or a radical STR3 in which R2 and R3 have the same meaning as above, R5 represents a lower alkyl radical and Alk represents a single bond or a straight- or branched-chain alkylene radical having from 1 to 4 carbon atoms. The invention also relates to a process for preparing 4-(3-amino-2-hydroxypropoxy)indole derivatives from the said 4-hydroxyindole derivatives.