| Identification | More | [Name]
4'-[[1,4'-Dimethyl-2'-propyl(2,6'-bi-1H-benzimidazol)-1'-yl]-methyl]-1,1'-biphenyl-2-carboxylic acid 1,1-dimethylethyl ester | [CAS]
144701-48-4 | [Synonyms]
RITOR
TU-199
MICARDIS
BIBR 277
Telmisaran
TIMISHATAN
BIBR 277SE
21829-25-4
TELMISARTAN
TIMETAZIDINE
TelMisartan API
Telmisartan99.5%
4'-[[1,4'-Dimethyl-2
Telmisartan (150 mg)
TelmisartanC33H30N402
TelMisartan (Micardis)
4'-(1,7'-Dimethyl-2'-propyl-1H-
4-chloromethyl-5-methyl-1,3-dioxol-2-tone | [EINECS(EC#)]
620-494-7 | [Molecular Formula]
C16H18N4O3S | [MDL Number]
MFCD00929085 | [Molecular Weight]
346.4 | [MOL File]
144701-48-4.mol |
| Chemical Properties | Back Directory | [Appearance]
White or off white crystalline powder | [Melting point ]
261-263°C | [Boiling point ]
771.9±70.0 °C(Predicted) | [density ]
1.16 | [RTECS ]
DV2037500 | [storage temp. ]
2-8°C | [solubility ]
DMSO: >5 mg/mL at 60 °C
| [form ]
solid
| [pka]
3.86±0.36(Predicted) | [color ]
white
| [Water Solubility ]
insoluble | [Usage]
An angiotensin II receptor antagonist | [Merck ]
14,9129 | [BCS Class]
2 | [Stability:]
Hygroscopic | [InChIKey]
RMMXLENWKUUMAY-UHFFFAOYSA-N | [SMILES]
C1(C2=CC=C(CN3C(CCC)=NC4=C(C)C=C(C5N(C)C6=CC=CC=C6N=5)C=C43)C=C2)=CC=CC=C1C(O)=O | [CAS DataBase Reference]
144701-48-4(CAS DataBase Reference) |
| Safety Data | Back Directory | [Hazard Codes ]
Xi | [Risk Statements ]
R36/37/38:Irritating to eyes, respiratory system and skin . | [Safety Statements ]
S22:Do not breathe dust .
S24/25:Avoid contact with skin and eyes .
S36:Wear suitable protective clothing .
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice . | [WGK Germany ]
2
| [HS Code ]
2933995300 | [Hazardous Substances Data]
144701-48-4(Hazardous Substances Data) |
| Hazard Information | Back Directory | [Description]
Telmisartan(cas:144701-48-4) was launched in the US for the treatment of hypertension.
It can be prepared in eight steps starting with methyl 4-amino-3-methyl
benzoate; the first and second cyclization into a benzimidazole ring occur at
steps 4 and 6 respectively. Telmisartan blocks the action of angiotensin II (Ang
II), the primary effector molecule of the renin-angiotensin-aldosterone system
(RAAS). It is the sixth of this class of 《sartans》 to be marketed after the lead
compound Losartan. Its long lasting effect (24h half-life) could be the main
difference with other angiotensin II antagonists. Unlike several other agents in
this category, its activity does not depend upon transformation into an active
metabolite, the 1-O-acylglucuronide being the principal metabolite found in
humans. Telmisartan is a potent competitive antagonist of AT1 receptors that mediate most of the important effects of angiotensin II while lacking affinity for
the AT2 subtypes or other receptors involved in cardiovascular regulation. In
several clinical studies, Telmisartan, at a once daily dosage, produced effective
and sustained blood-pressure lowering effects with a low incidence of side
effects (particularly treatment-related cough associated with ACE inhibitors in
elderly patients).
| [Originator]
Boehringer Ingelheim (Germany) | [Uses]
Telmisartan is an angiotensin II receptor antagonist that is primarily used for the treatment of hypertension. It can be used alone or in combination with other antihypertensive medications. Additionally, telmisartan is effective in treating diabetic nephropathy in hypertensive patients with type 2 diabetes mellitus. It is also utilized in the treatment of congestive heart conditions. | [Definition]
ChEBI: A member of the class of benzimidazoles used widely in the treatment of hypertension. | [Manufacturing Process]
A solution of 2.0 g (6.9 mMol) of 2-n-propyl-5-(1-methylbenzimidazol-2-yl)-
benzimidazole and 0.91 g (7.5 mmol) of potassium tert-butoxide in 50 ml of
dimethylsulfoxide is stirred for 90 min at room temperature, then 2.6 g (7.5
mMol) of tert-butyl 4'-bromomethyl-biphenyl-2-carboxylate are added and the
mixture is stirred for a further 15 h at room temperature. The mixture is then
poured onto 300 ml of water and extracted three times with 50 ml of ethyl
acetate. The crude product obtained after evaporation of the organic phase is
purified by column chromatography (300 g silica gel; eluant:methylene
chloride/methanol = 30:1). In this way, 2.7 g (70%) of an isomer mixture are
obtained (by NMR spectroscopy), contains about 1.18 g of tert-butyl-4'-[(2-npropyl-
5-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl)-methyl]biphenyl-2-
carboxylate and about 1.52 g of tert-butyl 4'-[(2-n-propyl-6-(1-
methylbenzimidazol-2-yl)-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate).
2.70 g of the isomer mixture obtained above are dissolved in 100 ml of
methylene chloride, mixed with 40 ml of trifluoroacetic acid and stirred for 4 h
at room temperature. The mixture is then evaporated to dryness in vacuo, the
residue is dissolved in 100 ml of 2 N sodium hydroxide solution, the solution
is washed with 50 ml of diethylether and the product mixture is precipitated
by acidifying the aqueous phase with acetic acid. By column chromatography
(400 g of silica gel, eluant:methylene chloride/methanol = 15:1) of the solid
thus obtained 0.9 g (74%) of 4'-[[2-n-propyl-6-(1-methylbenzimidazol-2-yl)-
benzimidazol-1-yl]methyl]biphenyl-2-carboxylate, melting point 217°-218°C.
| [Brand name]
Micardis (Boehringer Ingelheim). | [Therapeutic Function]
Antihypertensive | [General Description]
Telmisartan, 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid (Micardis, 144701-48-4), does not appear to bear any structuralrelationship to this class, but there is actually a great dealof overlap in the chemical architecture with other agents. Thefirst, and most significant, difference is the replacement of theacidic tetrazole system with a simple carboxylic acid. Thisacid, like the tetrazole, plays a role in receptor binding. Thesecond difference is the lack of a carboxylic acid near the imidazolenitrogen that also contributes to receptor binding.As with irbesartan, however, there is not a need for this groupto be acidic but, rather, to be one that participates in receptorbinding. The second imidazole ring, much like a purine basein deoxyribonucleic acid (DNA), can hydrogen bond with theangiotensin II receptor.
| [Biochem/physiol Actions]
Telmisartan is a non-peptide AT1 angiotensin receptor antagonist. | [Clinical Use]
Angiotensin-II antagonist:
Hypertension
Prevention of cardiovascular events | [Synthesis]
Telmisartan can be prepared in eight steps starting with methyl 4-amino-3-methyl benzoate; the first and second cyclization into a benzimidazole ring occur at steps 4 and 6 respectively.
 | [Drug interactions]
Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Analgesics: antagonism of hypotensive effect and
increased risk of renal impairment with NSAIDs;
hyperkalaemia with ketorolac and other NSAIDs.
Antihypertensives: increased risk of hyperkalaemia,
hypotension and renal impairment with ACE-Is and
aliskiren.
Cardiac glycosides: concentration of digoxin
increased.
Ciclosporin: increased risk of hyperkalaemia and
nephrotoxicity.
Diuretics: enhanced hypotensive effect;
hyperkalaemia with potassium-sparing diuretics.
ESAs: increased risk of hyperkalaemia; antagonism
of hypotensive effect.
Lithium: reduced excretion (possibility of enhanced
lithium toxicity).
Potassium salts: increased risk of hyperkalaemia.
Tacrolimus: increased risk of hyperkalaemia and
nephrotoxicity. | [Metabolism]
Telmisartan is metabolised by conjugation to the
glucuronide of the parent compound. No pharmacological
activity has been shown for the conjugate.
Telmisartan is excreted almost entirely in the faeces via
bile, mainly as unchanged drug. | [Clinical claims and research]
In several clinical studies, Telmisartan, at a once daily dosage, produced effective and sustained blood-pressure lowering effects with a low incidence of side effects (particularly treatment-related cough associated with ACE inhibitors in elderly patients). |
| Questions And Answer | Back Directory | [Chemical Properties]
White or off-white crystalline powder, odorless and tasteless. Soluble in chloroform, slightly soluble in methanol, very slightly soluble in acetone, practically insoluble in water. Slightly soluble in 0.1mol/L hydrochloric acid, soluble in 0.1mol/L sodium hydroxide.
Absorption coefficient（E1％1cm）：509～541
| [Mechanisms of Action]
80mg of telmisartan for the human body will practically completely counter the high blood pressure caused by angiotension II. Effects will last for 24 and can still be detected within 48 hours. Blood pressure-lowering effects should gradually become apparent within 3 hours after the initial dose. If treatment is suddenly interrupted, blood pressure will return to the same level as before treatment in a matter of days, and there will be no rebound high blood pressure. In a clinical trial that compared two kinds of antihypertensive drugs, patients in the treatment group experienced lower rates of coughing than those in the group treated by angiotensin converting enzyme inhibitors.
Telmisartan has a half-life of 18～24 hours, and will take effect 1～4 hours after taken. Medicinal effects can last for as long as 35 hours, with a high (T/P) ratio and outstanding effects in controlling morning blood pressure. Thus, this medicine can effectively control blood pressure for 24 hours, and it meets the once-daily medicinal standard (40～80mg, qd).
Clinical effects and characteristics:
- Pharmacokinetics show: Rapid effects (0.3h), long duration (35.4h), little effect on heart rate when lowering blood pressure.
- Compared to Enalapril: Stronger antihypertensive effects than Enalapril; when both are used in combination with diuretics, Telmisartan still appears to be superior and results in a lower coughing rate.
- Compared to Lisinopril: More apparent antihypertensive effects (for both systolic and diastolic blood pressure), coughing rate for Telmisartan (16%) is drastically lower than that of Lisinopril (60%).
- Compared to Atenolol: Similar antihypertensive effects, lower rate of side effects (impotence and fatigue).
- Compared to Amlodipine: The Telmisartan group experienced noticeably lower heart rates four hours after ingestion and from six a.m. to twelve p.m.
Overall, Telmisartan has the following characteristics in comparison with other antihypertensive medicine: specific receptor effects, noticeable hypertensive effects, good diuretic effects, improvement of myocardial stenosis, safe usage, good tolerance, and convenient daily dosage.
| [Side Effects]
In the placebo control experiment, the incidence rate of negative events for the Telmisartan group (41.4%) was similar to that of the placebo group (43.9%). Negative events were unrelated to dosage, sex, age, or race.
The following lists negative reactions were accumulated via the 5788 hypertensive patients that were treated with Telmisartan in the clinical trial.
Negative effects are categorized by incident rate as:
Very common (>1/10); common (>1/100, <1/10=); uncommon (>1/1000, <1/100=); rare (>1/10000, <1/1000=); very rare (<1/100000=)
Bodily reaction: Common: Back pain (e.g. sciatica), chest pain, flu-like symptoms, infection symptoms (e.g. urinary tract infection including cystitis). Uncommon: sight abnormality, sweating.
Central and peripheral nervous system: Common: vertigo.
Digestive system: Common: stomach pain, diarrhea, indigestion, gastrointestinal disorders. Rare: dry mouth, bloating.
Muscle skeletal system: Common: joint pain, leg cramps or leg pain, muscle pain. Rare: Tenosensitis symptoms.
Nervous system: Rare: anxiety.
Respiratory system: Common: upper respiratory tract infection, including pharyngitis and rhinitis.
Skin and accessory system: Common: Skin abnormalities such as eczema.
Additionally, since Telmisartan entered the market, there have been individual cases of erythema, itching, syncope, insomnia, depression, stomach discomfort, vomiting, hypotension, bradycardia, tachycardia, dyspnea, eosinophilia, thrombocytopenia, weakness, and reduced work efficiency. Similar to other angiotensin II receptor blockers, very few cases have reported vascular edema, nettles, and other negative reactions.
The laboratory found: compared to the placebo, the Telmisartan group occasionally exhibited lowered hemoglobin or raised uric acid. Any increase in serum creatinine or liver enzymes in the Telmisartan group was similar or lower than that of the placebo group.
| [Patent]
Telmisartan was originally formulated by the German pharmaceutical company Boehringer Ingelheim; it earned the German patent EP502,314 in 1991, was first approved to enter the American market in November 1998, and then entered German, Philippines, Australian, Belgium, British, and other markets.
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