Qualitative analysis of telmesertan

1.  Presented by : Kedar V. G  Guide by : Prof K. B. Gabhane
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2. Sr. No. Index Slide No.
1. Introduction 3 - 5
2. Mechanism of action 6
3. Abstract 7
4. Case study 8 - 17
5. Conclusion 18
6. Reference 19
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3.  Telmisartan is an angiotensin II receptor antogonist (ARB) used in the
management of high blood pressure.
 It is used in the treatment of essential hypertension.
 It has the extended half- life of any ARB (24 hours) [1] and the largest volume of
distribution among ARBs [2,3].
 Telmisartan is an effective antihypertensive agent with a tolerability profile
similar to that of placebo.
 It is as effective as other major classes of antihypertensive agents at lowering
blood pressure.
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4.  Structure
• It is chemically described as 2-(4-{[4-Methyl-6-(1-methyl-1H-1,3-
benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol
yl]methyl}phenyl)benzoic acid.
• Its empirical formula is C33H30N4O2.
• Its molecular weight is 514.63gm/mol.
• It is white to slightly yellowish solid.
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6.  Telmisartan interferes with the binding of angiotensin II to the angiotensin II
AT1-receptor by binding reversibly and selectively to the receptors in vascular
smooth muscle and the adrenal gland.
 As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and
release of aldosterone, blockage of its effects results in decreases in systemic
vascular resistance.
 Telmisartan does not inhibit the angiotensin converting enzyme, other hormone
receptors, or ion channels.
 Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of
angiotensin II by selectively blocking the binding of angiotensin II to the AT1
receptor in many tissues, such as vascular smooth muscle and the adrenal gland.
 Its action is therefore independent of the pathways for angiotensin II synthesis
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 The solid phase FTIR and FT-Raman spectra of Telmisartan have been recorded
in the regions 400 – 4000cm-1 and 400 – 4000cm-1 respectively.
 The spectra were interpreted in terms of fundamental modes, combination and
overtone bands.
 The structure of the molecule was optimized and the structural characteristics
were determined by Quantum chemical methods.
 The vibrational frequencies yield good agreement between observed and
calculated values.

9. Vibrational analysis of telmesertan
• The vibrational spectrum is mainly determined by the modes of the free molecule observed
at high wave numbers, together with the lattice (translational and vibrational) modes in the
low frequency region.
• In the present work, the frequency calculation analysis is performed to obtain the
spectroscopic signature of Telmisartan.
• It is a 69 atom molecule.
• It belongs to C1 symmetry having only identity operation.
• A molecule of n atoms has 3n degrees of freedom. 6-Mode of them is for translation and
rotational modes [23, 24].
• Hence, 201(3n-6) vibrational modes are observed in the molecule. The vibrational
assignments in the present work are calculated by and B3LYP method with 6-31G(d,p) and
6-311G(d,p) as basis sets.
• The observedFT-Raman and FTIR bands withtheir calculated wave numbers and
vibrational assignments are given in Table
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13.  To understand the observed spectral features, comparison of the observed and
simulated FTIR and FT-Raman spectra of entitled compound are presented in
Figures
1. FTIR spectra
2. FT-Raman
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17.  C-H Vibrations
 The C-H stretching vibrations of heterocyclic aromatic compound and its derivatives
generally occur in the region from 3000-3100cm-1[20,21,22].
 Hence in the present study, the C-H vibrations observed at 3028, 3047, 3055, 3070 and
3103cm-1 by B3LYP/6-31 G(d,p)method and those at 2991, 3020,3035,3050 and 3072cm-
1 were identified as C-H stretching vibrations.
 The C-H bending vibrations were found to be well within the characteristic region[23,
24].
 C-C vibrations
 Generally, the C-C stretching vibrations of aromatic compounds exhibit their
characteristic region 1430 to 1650cm-1[25,26].
 However, the actual positions are determined by the substitution around the aromatic
ring.
 In the present work, the experimental FT-Raman band observed at 1591cm-1and FTIR
bands observed at 1593cm-1 and that calculated at 1574cm-1 by B3LYP/6-31G(d,p) and
1599cm-1 by B3LYP/6-311G(d,p) were identified as C-C stretching vibrations.
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18. 1. C-N Vibrations
 The FTIR band calculated at 1249cm-1 and 1245cm-1 by both methods are
attributed as C-N stretching vibrations [27].
 The absorption of this band occurs at slightly higher frequency because of the
increase in the force constant of C-N bond which is increased by the resonance by
resonance with the ring.
1. O-H vibration
 The non-hydrogen bonded or free hydroxyl group of alcohols and phenols absorbs
strongly in the region from 3700-3584cm-1.
 The O-H group vibrations are likely to be the most sensitive to the environment.
Hence they show pronounced shifts in the spectra of the hydrogen bonded species.
 In the present work the bands observed at 3751cm-1 by B3LYP/6-31G(d,p)
method and that of 3803cm-1 by B3LY P/6-311G(d ,p) method are designated as
O-H stretching vibrations.
 These are in harmony with experimental wave numbers.
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19. 1. . In order to explain the electronic transitions of Telmisartan, theoretical
calculations on electronic absorption spectrum capable of describing the special
features of the molecule were performed using B3LYP/6-311G(d,p) level
2. . The experimental UV-spectrum of entitled compound was given in next Figure .
3. The calculated excitation energies, oscillator strength and λmax are reported in the
Table.
4. As seen from the table, the bands observed at 329.49nm and 304.15nm are due toπ
→ π*, where one of the electrons of unshared pair goes to an unstable (antibonding)
π* orbital.
5. The more intense band observed at 302.02m is due to n →π* whose oscillator
strength is obtained as 0.5225 which shows higher probability of transitions
between energy levels.
6. Thus with the calculated and observed outcomes give deep insight into the
electronic characteristics of Telmisartan.
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21.  In this study, the spectroscopic properties of Telmisartan was investigated by
FTIR, FT-Raman.
 Quantum chemical calculations such as B3LYP method with 6-31G(d,p) and 6-
311G(d,p) as basis sets help us to confirm the structural properties of the entitled
molecule.
 The comparative result of experimental and theoretical study gave as a complete
description of the geometry and vibrational properties of title molecule.
 In conclusion, all the obtained data not only show the way to the characterization
of the molecule but also help for the fundamental reseindustryl and novel
applications in technology and industry.
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22. [1] Benson S.C., Pershadsingh H., Ho C., Chittiboyina A., Desai P., Pravenec M., Qi
N., Wang J., Avery M. and Kurtz T. W., (2004). “Identification of Telmisartan as
a Unique Angiotensin II Receptor Antagonist with Selective PPAR -Modulating
Activity” Hypertension, Vol 43 (5), pp 993–1002.
[2] Biberachan der Riss, BoehringerIngelheimPharma KG and Biberach, Germany
(July 2000) “Pharmacokinetics of orally and intravenously administered
telmisartan in healthy young and elderly volunteers and in hypertensive
patients”, Journal of International Medical Research, Vol 28, pp 149-167.
[3] Philippe Gosse (September 2006) “A Review of Telmisartan in the Treatment of
Hypertension: Blood Pressure Control in the Early Morning Hours”,Vasc Health
Risk Manag.,Vol 2(3), pp 195-201.
[4] Andes HessJr. B., Lawrence J. Schaad, PetrCarsky andRudolf Zahradnik,(1986)
“Ab initio calculations of vibrational spectra and their use in the identification of
unusual molecules”Chemical Reviews,Vol86(4), pp 709-730.
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