55142-85-3

Usage

Uses

Used in Cardiovascular Applications:
Ticlopidine is used as an antiplatelet drug for the treatment of ischemic heart diseases. It suppresses the aggregation of thrombocytes and possesses antiaggregant activity, which is believed to be connected to its effect on thrombocyte membranes and the reduction in the quantity of released adenosine diphosphate and serotonin, which facilitate thrombocyte aggregation. In clinical trials, ticlopidine has demonstrated advantages over aspirin in treating cardiovascular conditions.
Used in Cerebrovascular Applications:
Ticlopidine is used in the secondary prevention of stroke, helping to reduce the risk of cerebrovascular events in patients with a history of stroke or transient ischemic attack (TIA). Its antiplatelet properties contribute to its effectiveness in this application.

Therapeutic Function

Platelet aggregation inhibitor

World Health Organization (WHO)

Ticlopidine, an inhibitor of platelet aggregation, was introduced in 1978 for use as an antithrombotic agent. By 1982 its use had been associated with cases of agranulocytosis, severe leucopenia and impaired haemostasis. The drug remains available in most countries in which it was approved with appropriate warnings in the product information.

Synthesis

Ticlopidine, 5-(o-chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (24.2.1), is synthesized in many different ways. The first way consists of N-alkylation of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine with 2-chlorobenzylchloride.

InChI:InChI=1/C14H14ClNS/c15-13-4-2-1-3-11(13)9-16-7-5-14-12(10-16)6-8-17-14/h1-4,6,8H,5,7,9-10H2

Upstream product

• 54903-50-3 4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 611-19-8 1-chloro-2-(chloromethyl)benzene 
• 79714-07-1 5-(2-chloro-benzyl)-5,6-dihydro-4H-thieno[3,2-c]pyridin-7-one; hydrochloride 
• 34846-44-1 3-Bromomethylthiophene 
• 79714-11-7 [(Thiophen-3-ylmethyl)-amino]-acetic acid ethyl ester 
• 88720-42-7 N-<(2-chlorophenyl)methyl>glycine ethyl ester 
• 79714-00-4 N-<(2-chlorophenyl)methyl>-N-(3-thenyl)glycine ethyl ester 
• 79714-04-8 [(2-Chloro-benzyl)-thiophen-3-ylmethyl-amino]-acetic acid; hydrochloride 
• 41661-47-6 piperidin-4-one 
• 135576-51-1 1-(2-chlorobenzyl)-4-piperidone 
• 865187-82-2 2-(2-bromoethyl)-3-(bromomethyl)thiophene 
• 89-97-4 2-CHLOROBENZYLAMINE 
• 128988-10-3 1-[(2-chlorophenyl)methyl]-4-oxo-3-piperidine acetaldehyde 
• 50-00-0 formaldehyd 

Downstream Products

• 73099-83-9 2-chloro-5-(2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine 
• 90997-36-7 2-(2-Chloro-benzyl)-8-[5-(2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-2-yl]-6-eth-(E)-ylidene-7-methyl-2,3,4,6-tetrahydro-1H-cyclopenta[4,5]thieno[3,2-c]pyridine 
• 90997-27-6 1-[5-(2-Chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-2-yl]-propan-1-one 
• 90997-25-4 1-[5-(2-Chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-2-yl]-ethanone 
• 90997-29-8 1-[5-(2-Chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-2-yl]-butan-1-one 
• 90997-31-2 1-[5-(2-Chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-2-yl]-heptan-1-one 
• 68559-55-7 5-(2-chloro-benzyl)-6,7-dihydro-5H-thieno[3,2-c]pyridin-4-one 
• 1056463-57-0 5-(o-chlorobenzyl)-2-formyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 1056463-59-2 dimethyl (E)-2-[(o-chlorobenzyl)-2-(3-methoxymethylthiophen-2-yl)ethylamino]but-2-ene-1,4-dioate 
• 444728-11-4 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridine-5(4H)-yl)acetonitrile 
• 83427-51-4 5-(2-Chlorobenzyl)-5,6,7,7a-tetrahydro-4H-thieno(3,2-c)-pyridin-2-one 
• 90997-72-1 [5-(2-Chloro-benzyl)-2-ethyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-3-yl]-[4-(2-dibutylamino-ethoxy)-phenyl]-methanone 
• 90997-70-9 [5-(2-Chloro-benzyl)-2-ethyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-3-yl]-[4-(2-diethylamino-ethoxy)-phenyl]-methanone 

Relevant academic research and scientific papers

Inhibition of platelet activation, aggregation and/or adhesion by hypothermia

A method for treating acute coronary syndromes (i.e., unstable angina or non-Q-wave MI) or transient ischemic attacks in a human or animal patient by placing a heat exchange apparatus in the patient's vasculature and using that heat exchange apparatus to cool the patient to a temperature (e.g. 30-36 degrees C.) at which platelet inhibition (i.e., inhibition of platelet activation and/or aggregation and/or adhesion) occurs. Anti-shivering drugs or anesthesia may be administered to patients whose body temperature is cooled below that patient's shivering threshold (typically approximately 35.5 degrees C.). If it is determined that platelet inhibition is no longer desirable, such as when the patient is about to undergo a surgical or interventional procedure wherein bleeding could be problematic, the hypothermia-induced platelet inhibition may be rapidly reversed by using the intravascular heat exchange apparatus to re-warm the patient's body to normothermia or near normothermia.

2-Chlorophenyl zinc bromide: A convenient nucleophile for the mannich-related multicomponent synthesis of clopidogrel and ticlopidine

A methodological study devoted to the Mannich-like multicomponent synthesis of the antiplatelet agent (±)-clopidogrel (7) and the ethyl ester analogue 6 is described. The process involves the formation of 2-chlorophenyl zinc bromide (2) and its subsequent reaction with an alkyl glyoxylate and 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (3). We demonstrate that the organozinc reagent 2 also constitutes a very convenient nucleophile for the multicomponent synthesis of the benzylamine core of ticlopidine (9).

METHOD OF PREPARING THIENO[3,2-C]PYRIDINE DERIVATIVES AND INTERMEDIATES USED THEREIN

Ticlopidine and clopidogrel having high blood platelet aggregation inhibitory and anti-thrombotic activities are simply prepared by reacting a substituted thiophene derivative with a 2-chlorobenzylamine derivative.

MEDICINAL COMPOSITION

A pharmaceutical composition containing a drug (A), a waxy substance (B), and synthetic aluminum silicate and/or hydrous silicon dioxide (C). The invention provides a granular pharmaceutical composition suitable for providing a pharmaceutical characterized in that adhesion of granules thereof onto a granulation apparatus during granulation is minimized and caking of the granules is suppressed.

MEDICINAL COMPOSITIONS

The present invention relates to a granular pharmaceutical composition comprising a drug having a disagreeable taste, a wax and a sugar alcohol; a method for preparing the same; and a pharmaceutical product for oral administration, comprising the granular composition. The product excellently masks a disagreeable taste possessed by a drug and provides good sensation upon oral administration, and therefore is easily ingested by even the elderly, children, and patients suffering dysphagia. Moreover, the product is suitable for administration using tube.

Preparation of 2-(2-thienyl) ethylamine and synthesis of thieno [3,2-C] pyridine derivatives therefrom

Compounds of the formulae:and wherein:, R1, R2, R3 and R4 are independently hydrogen, lower alkyl of one to six carbon atoms, aryl or substituted aryl;, are advantageously converted to isocyanurate compounds, 2-(2-thienyl)ethylamine compounds and thieno[3,2-c]pyridine derivatives and the pharmaceutically acceptable salts thereof, particularly ticlopidine hydrochloride.

2-thienylglycidic derivative, process for its preparation and its use as synthesis intermediate

The invention relates to isopropyl 2-thienylglycidate of formula: STR1 obtained by reaction of 2-thienylcarboxaldehyde with an isopropyl haloacetate. It is employed as a synthesis intermediate in the preparation of 2-thienylacetaldoxime and of medications derived from thieno[3,2-c]pyridine.

Carbamate salts of 2-(2'-thienyl)alkylamines

The carbamate salt of 2-(2'-thienyl)-alkylamines and particularly the ethylamine and its method of synthesis are disclosed. The carbamate salt of 2-(2'-thienyl)ethylamine is a stable, easily transportable crystalline material that can be converted to 2-(2'-thienyl)ethylamine, a useful intermediate in the synthesis of 5[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno-[3,2-c]pyridine hydrochloride, also known as ticlopidine hydrochloride. The synthesis is carried out by reacting an amine of formula (I): STR1 with CO2 in a hydrocarbon solvent to obtain the carbamate salt of formula II: STR2

USE OF MERCAPTOACETALDEHYDE DIMER IN A NOVEL THIENOANNELATION SEQUENCE. A SHORT SYNTHESIS OF TICLOPIDINE

A short synthesis of ticlopidine (1) was achieved by condensation of mercaptoacetaldehyde dimer (2) with piperidone (3b) in the presence of lithium diisopropylamide followed by dehydration.

2-(2-nitrovinyl)thiophene reduction and synthesis of thieno[3,2-c]pyridine derivatives

An improved process for the reduction of 2-(2-nitrovinyl)thiophene to form 2-(2-thienyl)ethylamine employs a boron-containing reducing agent, preferably diborane. The 2-(2-thienyl)ethylamine produced by this process is advantageously converted to ticlopidine.