63590-64-7

Usage

Uses

1. Hypertension Treatment:
Terazosin is used as an antihypertensive agent for the treatment of high blood pressure. It works by blocking the action of the hormone adrenaline, which causes blood vessels to narrow, thus allowing for better blood flow and reducing blood pressure.
2. Benign Prostatic Hyperplasia (BPH):
Terazosin is used as a medication for the treatment of BPH, a condition where the prostate gland becomes enlarged, causing difficulty in urinating. It helps to relax the muscles in the prostate and bladder neck, improving urine flow.
3. Once-a-Day Administration:
One of the advantages of Terazosin is its long-lasting effect, which allows it to be administered once a day. This makes it a more convenient option for patients compared to other medications that may require multiple daily doses.
4. Cardiovascular Applications:
Terazosin is used as a vasodilator in the cardiovascular industry, helping to improve blood flow and reduce the workload on the heart. This can be beneficial for patients with heart conditions or those at risk of developing cardiovascular diseases.

Clinical Use

Alpha-adrenoceptor blocker: Hypertension Benign prostatic hyperplasia (BPH)

Synthesis

Terazosin, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)- piperazine (12.2.13), only differs from prazosin in that the furyl radical is replaced with a tetrahydrofuryl radical. It is synthesized in exactly the same manner except using 1-(2-tetrahydrofuroyl)piperazine instead of 1-(2-furoyl)piperazine [48–51].

Drug interactions

Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Antidepressants: enhanced hypotensive effect with MAOIs. Avanafil, vardenafil, sildenafil and tadalafil: enhanced hypotensive effect - avoid concomitant use. Beta-blockers: enhanced hypotensive effect; increased risk of first dose hypotensive effect. Calcium-channel blockers: enhanced hypotensive effect; increased risk of first dose hypotensive effect. Diuretics: enhanced hypotensive effect; increased risk of first dose hypotensive effect. Moxisylyte: possibly severe postural hypotension when used in combination.

Metabolism

Terazosin is metabolised in the liver; one of the metabolites has antihypertensive activity. Terazosin is excreted in faeces via the bile, and in the urine, as unchanged drug and metabolites.

InChI:InChI=1/C19H25N5O4.ClH.2H2O/c1-26-15-10-12-13(11-16(15)27-2)21-19(22-17(12)20)24-7-5-23(6-8-24)18(25)14-4-3-9-28-14;;;/h10-11,14H,3-9H2,1-2H3,(H2,20,21,22);1H;2*1H2/p-1

Synthetic route

tetrahydro-2-furancarboxylic acid (16874-33-2) + 4-amino-6,7-dimethoxy-2-piperazin-1-ylquinazoline (60547-97-9) → terazosin (63590-64-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; ethyl cyanoglyoxylate-2-oxime In N,N-dimethyl-formamide at 20℃;	65%

prazosin hydrochloride (19237-84-4) → terazosin (63590-64-7)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol; water at 20℃;

2-chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4) + N-(tetrahydro-2-furoyl)-piperazine (63074-07-7) → terazosin (63590-64-7)

Methyl Cellosolve (ethylene glycol monomethyl ether) + ammonium hydroxide + 2-chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4) + N-(tetrahydro-2-furoyl)-piperazine (63074-07-7) → terazosin (63590-64-7)

Conditions	Yield
In water	84 grams (87%)
In water	90.8 grams (94%)
With triethylamine In water

1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-4-[[(2RS)2,3,4,5-tetrahydrofuran-2-yl]carbonyl]piperazine hydrochloride hydrobromide (943644-21-1) → terazosin (63590-64-7)

Conditions	Yield
With ammonia In water at 25 - 45℃; for 1h; pH=8.4;

terazosin (63590-64-7) → terazosin hydrochloride

Conditions	Yield
With hydrogenchloride for 2.86667h;
With hydrogenchloride In ethanol; water at 60 - 65℃; for 0.25h;

Upstream product

• 23680-84-4 2-chloro-6,7-dimethoxyquinazolin-4-amine 
• 63074-07-7 N-(tetrahydro-2-furoyl)-piperazine 
• 16874-33-2 tetrahydro-2-furancarboxylic acid 
• 60547-97-9 4-amino-6,7-dimethoxy-2-piperazin-1-ylquinazoline 
• 943644-21-1 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-4-[[(2RS)2,3,4,5-tetrahydrofuran-2-yl]carbonyl]piperazine hydrochloride hydrobromide 
• 19237-84-4 prazosin hydrochloride 

Relevant academic research and scientific papers

A facile synthesis of [tetrahydrofuran-3H] terazosin

An efficient synthesis of [3H] terazosin at high specific activity from prazosin is described.

Targeting Influenza A Virus RNA Promoter

The emergence of drug-resistant strains of influenza virus makes exploring new classes of inhibitors that target universally conserved viral targets a highly important goal. The influenza A viral genome is made up of eight single-stranded RNA-negative segments. The RNA promoter, consisting of the conserved sequences at the 3′ and 5′ end of each RNA genomic segment, is universally conserved among influenza A virus strains and in all segments. Previously, we reported on the identification and NMR structure of DPQ (6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine) (compound 1) in complex with the RNA promoter. Here, we report on additional screening and SAR studies with compound 1, including ex vivo anti-influenza activity assays, resulted in improved cellular activity against influenza A virus in the micromolar range.

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.

Process for the preparation of terazosin hydrocloride dihydrate

The present invention relates to an improved process for the preparation of 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-4-[[(2RS)-2,3,4,5-tetrahydrofuran-2-yl]carbonyl]piperazine hydrochloride dihydrate of Formula I, through an intermediate 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-4-[[(2RS)-2,3,4,5-tetrahydrofuran-2-yl]carbonyl]piperazine hydrochloride/hydrobromide (V).

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.

Preparation of amides and quinazoline derivatives

The present invention relates to a process for the preparation of amides, comprising reacting amines with carboxylic acids in the presence of silicon amines. The present invention further relates to a process for the preparation of quinazoline derivatives, comprising reacting amines with carboxylic acids in the presence of silicon amines to obtain amides and contacting the resultant amides with quinazoline.

Process and intermediate for the preparation of terazosin hydrochloride dihydrate

A process for the preparation of 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)piperazine hydrochloride (terazosin hydrochloride dihydrate comprises the steps of reacting 4-amino-2-chloro-6,7-dimethoxy-quinazoline with N-(2-tetrahydrofuroyl)piperazine in an anhydrous polar organic solvent in the absence of an added acid scavenger to produce anhydrous 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)piperazine hydrochloride (Form IV) and thereafter converting the product of that step to 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)-piperazine hydrochloride dihydrate.

Terazosin polymorph and pharmaceutical composition

A process for preparing a novel anhydrous crystalline polymorph of anhydrous 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(tetrahydro-2-furoyl)piperazine monohydrochloride comprises contacting the known amorphous, crystalline dihydrate, or crystalline anhydrous form I of the compound with a polar organic solvent.

1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)piperazine hydrochloride dihydrate

An improved anti-hypertensive agent, the hydrochloride salt of 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)piperazine dihydrate.