1197-18-8 Usage
Uses
Used in Pharmaceutical Quality Control:
Amstat is used as a secondary standard for ensuring the quality and consistency of pharmaceutical products. It helps in the development and validation of analytical methods, as well as in the preparation of in-house working standards.
Used as a Lysine Analogue:
Amstat is used as a lysine analogue to characterize binding sites in plasminogen. This application aids in understanding the interactions between plasminogen and other molecules, which can be crucial for the development of new therapeutic strategies.
Used in Fibrinolysis Inhibition:
Amstat is used in the inhibition of fibrinolysis, the cleavage of fibrin by plasmin, which is a normal step in the dissolution of fibrin clots after wound repair. It acts as a lysine mimetic, binding to the lysine binding site in plasmin and blocking its interaction with fibrin. Antifibrinolytic agents, like Amstat, are valuable when fibrinolytic activity is abnormally high or when coagulation is impaired.
Used in Different Industries:
Amstat may have various applications in different industries, such as pharmaceuticals, biotechnology, and medical research. Each industry may utilize Amstat for different purposes based on its specific needs and requirements.
Properties
Amstat is an antifibrinolytic drug, commonly called Tranexamic acid. Tranexamic acid is a white crystalline powder. It is freely soluble in water and in glacial acetic acid and is very slightly soluble in ethanol and practically insoluble in ether.
Coagulation and hemostasis drugs
Tranexamic acid is a derivative of aminomethylbenzoic acid, and a kind of antifibrinolytic drugs to stop bleeding. The hemostasis mechanism of tranexamic acid is similar to aminocaproic acid and aminomethylbenzoic acid, but the effect is stronger. The strength is 7 to 10 times of aminocaproic acid, 2 times of aminomethylbenzoic acid, but toxicity is similar.
The chemical structure of tranexamic acid is similar to lysine, competitive inhibition of plasmin original in fibrin adsorption, to prevent their activation, protection fiber protein not to degrade by plasmin and dissolve, eventually achieve hemostasis. Applicable in the treatment of acute or chronic, localized or systemic primary fiber fibrinolytic hyperthyroidism caused by bleeding, such as obstetric hemorrhage, renal hemorrhage, hemorrhage of hypertrophy of the prostate, hemophilia, pulmonary tuberculosis hemoptysis, stomach bleeding, after operation of liver, lung, spleen and other viscera hemorrhage; also can be used in surgery when abnormal bleeding etc..
Clinical tranexamic acid has effect significantly to insect bites disease, dermatitis and eczema, simple purpura, chronic urticaria, artificial sex urticaria, toxic eruption and eruption. And also has a certain effect on erythroderma, scleroderma, systemic lupus erythematosus (SLE), Erythema multiforme, shingles and alopecia areata. Treatment of hereditary angioedema effect is also good. In the treatment of Chloasma, general medicine is effective about 3 weeks, markedly effective 5 weeks, a course of 60 days. Given orally in doses of 0.25 ~ 0.5 g, a day 3 ~ 4 times. A few patients can nausea, fatigue, pruritus, abdominal discomfort, and diarrhea side effects after withdrawal symptoms disappear.
Indications
Various bleedings caused by acute or chronic, localized or systemic primary hyperfibrinolysis; secondary hyperfibrinolytic state caused by disseminated intravascular coagulation. Generally do not use this product before heparinization.
Trauma or surgical bleeding in tissue and organs with abundant plasminogen activators such as prostate, urethra, lung, brain, uterus, adrenal glands, and thyroid.
An antagonist of tissue plasminogen activator (t-PA), streptokinase, and urokinase.
Fibrinolytic hemorrhage caused by artificial abortion, early placental detachment, stillbirth and amniotic fluid embolism; and increased menorrhagia caused by pathological intrauterine fibrinolysis.
Cerebral neuropathy mild bleeding, such as subarachnoid hemorrhage and intracranial aneurysm hemorrhage, the effect of Amstat in this condition is better than that of other anti-fibrinolytic agents. Special attention must be paid to the risk of cerebral edema or cerebral infarction. ?For severe patients with surgical indications, this product can only be used as an adjuvant drug.
For the treatment of hereditary angioneurotic edema, it can reduce the number and severity of episodes.
Used in patients with hemophilia for their active hemorrhage in combination with others drug.
Hemophilia patients with factor VIII or factor IX deficiency in their tooth extraction or oral surgery in case of operating bleeding.
Mechanism of action
Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin’s matrix structure.
Mechanism of action
Tranexamic acid can also be viewed as a structural analog of lysine. It is presumed that it
works by the same mechanism as aminocaproic acid; however, it is 6–10 times more
active. It inhibits action of a plasmin and plasminogen inhibitor, and has a hemostatic
effect.
Pharmacokinetics
After a single oral administration of two 650 mg tablets of LYSTEDA, the peak plasma concentration (Cmax ) occurred at approximately 3 hours (Tmax ). The absolute bioavailability of LYSTEDA in women aged 18-49 is approximately 45%. Following multiple oral doses (two 650 mg tablets three times daily). administration of LYSTEDA for 5 days, the mean C max increased by approximately 19% and the mean area under the plasma concentration-time curve (AUC) remained unchanged, compared to a single oral dose administration (two 650 mg tablets). Plasma concentrations reached steady state at the 5th dose of LYSTEDA on Day 2.
Side effects
The table below contains some of the side-effects associated with tranexamic acid, although these occur only rarely.
▼▲
Tranexamic acid side-effects
What can I do if I experience this?
Feeling or being sick
Stick to simple meals avoid rich and spicy food. If you are not already doing so, try taking the tablets after meals
Diarrhoea
Drink plenty of water to replace the lost fluids
Eyesight problems (such as problems with your colour vision)
Let your doctor know about this as soon as possible as your treatment will need to be reviewed
Originator
Anvitoff,Knoll,W. Germany,1967
Manufacturing Process
In an autoclave, 2 grams of a mixture of cis- and trans-4-
aminomethylcyclohexane-1-carboxylic acid, which is obtained by catalytic
reduction of p-aminomethylbenzoic acid in the presence of platinum catalyst
and contains 60% by weight of cis-isomer was reacted at 200°C, for 8 hours
with 20 ml of ethyl alcohol in which 0.44 gram of sodium metal had been
dissolved. After cooling, the reaction solution was concentrated under a
reduced pressure to give a white residue. This residue was dissolved in 40 ml
of water and passed through a column of a strongly acidic cation ion_x0002_exchanger resin (NH4+). The eluate was concentrated under reduced pressure
to form a white mass. An adequate amount of acetone was added thereto and
1.95 grams of white powder was obtained. This powder was recrystallized
from water-acetone to give 1.85 grams (yield, 92.5%) of white crystalline
powder having a melting point of 380° to 390°C (decomposition). This
product was identified as trans-4-aminomethylcyclohexane-1-carboxylic acid
by means of infrared spectrum.
Therapeutic Function
Coagulant
Flammability and Explosibility
Notclassified
Clinical Use
Haemostatic agent
Synthesis
Tranexamic acid, trans-4-(aminomethyl)cyclohexane carboxylic acid
(24.4.5), is synthesized from 4-methylbenzonitrile. Oxidation of the methyl group gives
the mononitrile of terephthalic acid 24.4.2. The cyano group in Amstat is reduced
by hydrogen using Raney nickel as a catalyst. The benzene ring of the resulting 4-
aminomethylbenzoic acid (24.4.3) is reduced to a cyclohexane moiety by hydrogen and a
platinum catalyst, which forms an isomeric mixture of 4-aminomethylcyclohexane carboxylic
acids (24.4.4), and the desired trans-isomer 24.4.5 is isolated by crystallization of
the mixture of its sodium salts.
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Tranexamic acid is excreted as unchanged drug mainly by urinary excretion via glomerular filtration.
Check Digit Verification of cas no
The CAS Registry Mumber 1197-18-8 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,1,9 and 7 respectively; the second part has 2 digits, 1 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1197-18:
(6*1)+(5*1)+(4*9)+(3*7)+(2*1)+(1*8)=78
78 % 10 = 8
So 1197-18-8 is a valid CAS Registry Number.
InChI:InChI=1/C8H15NO2/c9-5-6-1-3-7(4-2-6)8(10)11/h6-7H,1-5,9H2,(H,10,11)/t6-,7-
1197-18-8Relevant articles and documents
Method for synthesizing formic acid
-
, (2022/04/03)
The invention discloses a synthesis process of tranexamic acid (I), which comprises the following steps of: performing esterification reaction on 3-cyclohexene formic acid (V) serving as a raw material to obtain an intermediate 3-cyclohexene formate (IV); carrying out carbonyl insertion reaction on the intermediate (IV) and carbon monoxide/hydrogen mixed gas or synthesis gas in the presence of a catalyst to obtain an intermediate 4-formyl cyclohexane-1-formate (III) with high selectivity; carrying out reductive amination on the intermediate (III) to obtain an intermediate 4-aminomethyl cyclohexane formate (II); and finally hydrolyzing and transforming the intermediate (II) to obtain tranexamic acid (I). The raw materials are cheap and easy to obtain, the carbon monoxide carbonyl insertion reaction is green and environment-friendly, the route is simple and efficient, and a new method is provided for synthesis of tranexamic acid (I).
READY-TO-USE TRANEXAMIC ACID INTRAVENOUS SOLUTION
-
, (2020/04/09)
Ready-to-use, stable aqueous intravenous tranexamic acid compositions are provided.
A 4-acetamidomethyl methyl cyclohexyl method for producing methyl formate
-
Paragraph 0051-0053, (2017/02/28)
The invention relates to a preparation method of methyl 4-acetylaminomethyl hexahydrobenzoate. The method comprises the following steps: adding methyl paracyanobenzoate into a reaction kettle, adding a metal catalyst I and a cocatalyst II, heating while stirring to react under hydrogen gas conditions for 6-10 hours by using acetic anhydride as a solvent, filtering, and distilling to obtain the methyl acetylaminomethyl benzoate; and adding the obtained methyl acetylaminomethyl benzoate into a reaction kettle, adding a solvent V, a metal catalyst III and a cocatalyst IV, heating while stirring to completely react under hydrogen gas conditions, filtering, and distilling to recover the solvent, thereby obtaining the methyl 4-acetylaminomethyl hexahydrobenzoate. The synthesis technique of preparing the methyl 4-acetylaminomethyl hexahydrobenzoate from the initial raw material methyl paracyanobenzoate has the advantages of accessible raw materials, low cost, high yield and the like, and is simple to operate and suitable for industrial production. The product can be further used for preparing the trans-4-aminomethylcyclohexyl formic acid, and has huge application potential.
Design, synthesis and in vitro kinetic study of tranexamic acid prodrugs for the treatment of bleeding conditions
Karaman, Rafik,Ghareeb, Hiba,Dajani, Khuloud Kamal,Scrano, Laura,Hallak, Hussein,Abu-Lafi, Saleh,Mecca, Gennaro,Bufo, Sabino A.
, p. 615 - 635 (2013/09/02)
Based on density functional theory (DFT) calculations for the acid-catalyzed hydrolysis of several maleamic acid amide derivatives four tranexamic acid prodrugs were designed. The DFT results on the acid catalyzed hydrolysis revealed that the reaction rate-limiting step is determined on the nature of the amine leaving group. When the amine leaving group was a primary amine or tranexamic acid moiety, the tetrahedral intermediate collapse was the rate-limiting step, whereas in the cases by which the amine leaving group was aciclovir or cefuroxime the rate-limiting step was the tetrahedral intermediate formation. The linear correlation between the calculated DFT and experimental rates for N-methylmaleamic acids 1-7 provided a credible basis for designing tranexamic acid prodrugs that have the potential to release the parent drug in a sustained release fashion. For example, based on the calculated B3LYP/6-31G(d,p) rates the predicted t1/2 (a time needed for 50 % of the prodrug to be converted into drug) values for tranexamic acid prodrugs ProD 1-ProD 4 at pH 2 were 556 h [50.5 h as calculated by B3LYP/311+G(d,p)] and 6.2 h as calculated by GGA: MPW1K), 253 h, 70 s and 1.7 h, respectively. Kinetic study on the interconversion of the newly synthesized tranexamic acid prodrug ProD 1 revealed that the t1/2 for its conversion to the parent drug was largely affected by the pH of the medium. The experimental t1/2 values in 1 N HCl, buffer pH 2 and buffer pH 5 were 54 min, 23.9 and 270 h, respectively. Graphical Abstract: [Figure not available: see fulltext.]
NOVEL MULTIMERIC MOLECULES, A PROCESS FOR PREPARING THE SAME AND THE USE THEREOF FOR MANUFACTURING MEDICINAL DRUGS
-
, (2010/06/16)
The invention relates to a compound of the formula (I): in which k and j are independently 0 or 1, Y is a macrocycle in which the cycle includes 9 to 36 carbon atoms and is functionalised by three amino functions and by a chain for attaching the spacer arm Z via an X bond, Rc is a binding pattern with a receptor of the TNF superfamily, X is a chemical function for binding the Y group to the space arm, and Z is a bi-, tri- or tetra-functional spacer arm.
NOVEL MULTIMERIC CD40 LIGANDS, METHOD FOR PREPARING SAME AND USE THEREOF FOR PREPARING DRUGS
-
, (2010/08/07)
The invention concerns a compound of formula (I), wherein Y represents a macrocycle whereof the cycle comprises 9 to 36 atoms, and is functionalized by three amine or COOH functions; Rc represents a group of formula H—Xa—Xb—Xc—Xd—Xe—(Xf)i—, wherein i represents 0 or 1, Xn is in particular selected among lysine, arginine, ornithine residues, Xb is in particular selected among glycine, asparagine, L-proline or D-proline residues, Xc et Xd are in particular selected among tyrosine, phenylalanine or 3-nitrotyrosine residues, Xe et Xf are in particular selected among the following amino acid residues: NH2—(CH2)n—COOH, n ranging from 1 to 10 or NH2—(CH2—CH2—O)m—CH2CH2COOH, m ranging from 3 to 6, provided that one at least of the amino acid residues Xa, Xb, Xc and Xd is different from the corresponding amino acid in the sequence of the natural CD40 143Lys-Gly-Tyr-Tyr146 fragment
2-aminopyridine derivatives and combinatorial libraries thereof
-
, (2008/06/13)
The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.
Method for the production of trans-4-aminomethyl cyclohexane-1-carboxylic acid
-
, (2008/06/13)
Disclosed is a method for producing trans-4-aminomethyl cyclohexane-1-carboxylic acid by heating and isomerizing cis-4-aminoethyl cyclohexane-1-carboxylic acid hydrochloride or a mixture of cis-4-aminomethyl cyclohexane-1-carboxylic acid hydrochloride with trans-4-aminomethyl cyclohexane-1-carboxylic acid hydrochloride in an atmosphere of hydrogen chloride gas and in the absence of a solvent.
Trans-4-aminomethylcyclohexane-1-carboxylic acid
-
, (2008/06/13)
A trans isomer of 4-cyanoncyclohexane-1-carboxylic acid or its lower alkyl ester is reduced in a solvent in the presence of a hydrogenating catalyst, and hydrolyzing the produced ester in case the starting trans-isomer is a lower alkyl ester, then the trans-4-aminomethyl-cyclohexane-1-carboxylic acid is recovered from the reaction mixture.
