“SYNTHESIS AND EVALUATION OF SOME NOVEL FEXOFENADINE ANALOGUES FOR THEIR ANTIHISTAMINIC AND ANTIBACTERIAL ACTIVITY”
M.PHARM DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE.
BY,
BOBADE SIDHAVINAYAK VITHALRAO
B.Pharm.
UNDER THE GUIDANCE OF,
Dr. N.K. SATHISH
M.Pharm.,Ph.D.,
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
SAC COLLEGE OF PHARMACY
B. G. NAGARA
KARNATAKA -571448
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
ANNEXURE-II
1 / Name of the candidate & Address / MR. SIDHAVINAYAK VITHALRAO BOBADES.A.C. COLLEGE OF PHARMACY
B. G. NAGARA-571448
NAGMANGLA(TALUK)
MANDYA (DIST)
KARNATAKA
PERMANENT ADDRESS:
A/P- LAKHANGAON
TALUKA – BHALKI
DIST.- BIDAR
PIN NUMBER-585411
STATE-KARNATAKA
2 / Name of the institute / S.A.C. COLLEGE OF PHARMACY
B.G.NAGARA
KARNATAKA -571448
3 / Course of the study / M. PHARM IN PHARMACEUTICAL CHEMISTRY
4 / Date of admission / 17-06-2009
5 / Title of the topic / SYNTHESIS AND EVALUATION OF SOME
NOVEL FEXOFENADINE ANALOGUES FOR
THEIR ANTIHISTAMINIC AND ANTIBACTERIAL
ACTIVITY
Enclousure-I
6 Brief resume of intended work:
6.1 Introduction:
Fexofenadine hydrochloride (brand names include Allegra and Telfast) is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms. It was developed as a successor and alternative to terfenadine (brand names include Triludan and Seldane), an antihistamine with potentially serious contraindications. Fexofenadine, like other second and third-generation antihistamines does not readily cross the blood-brain barrier, and so causes less drowsiness than first-generation histamine-receptor antagonists. It works by being an antagonist to the H1 receptor. It has been described as both second-generation and third-generation antihistamines.
Histamine plays a major role on allergy. Prevention and treatment of allergy has become an important area of research from many years. The primary objective of anti-histaminic research over the past two decades is focused on the development of new drugs with higher selectivity towards H1 receptors with less CNS depressant action. Later, these efforts led to the introduction of second generation anti-histamines such as loratidine, citrizine, cinnarizine, astemazole and terfenadine which are proved to be safe and efficacious drugs in the treatment of allergy but have severe cadiovascularside effects when used in conjugation with antifungal or antibacterial agents and it is widely used for the treatment of allergy. In view of the above facts, we have planned to synthesize novel fexofenadine analogue for their antihistaminic with all side effects and antibacterial activity.
6.2 Review of the literature:
Qun K. Fang, et al1 reported an efficient and practical method for synthesis of racemic and optically active Fexofenadine. The key racemic or optically active lactol intermediate is prepared from readily available tolyl derivative and suggest that (S)-terfenadine may have improved therapeutic characteristics compared to the racemate.
Stephan h. kawai, et al2 reported the drugs which alter hepatic oxidative metabolism cause an accumulation of Terfenadine by preventing its metabolism to carboxyterfenadine.
Sathish N.K, et al3 have Synthesized by Friedel Craft acylation, Grignard reaction, condensation and reduction. The analogues shown significant anti-histaminic activity by inhibiting contraction induced by histamine on guinea pig ileum.
Sathish N.K, et al4 have synthesized by Friedel Craft acylation, Grignard reaction, condensation and reduction. The analogues shown significant anti-histaminic activity by inhibiting contraction induced by histamine on guinea pig ileum, anti-cholinergic by guinea pig tracheal chain and sedative activities..
Breier A.R, et al5 have reported the stress studies revealed the photostability of the drug as the most adverse stability factor. The results show the importance of appropriate light protection during the drug development process, storage and handling.
Sathish N.K, et al6 have reported efficient and practical analogues synthesis of Fexofenadine by Friedal Craft acylation and condensation reaction and evaluated for anti-histaminic and sedative activity.
6.3 Objectives of the study:
1. Synthesis of some novel Fexofenadine analogues.
2. The purification of the compounds will be carried by recrystallization using suitable solvents, TLC, Column Chromatography, etc.
3. Characterization of newly synthesized compounds by UV, IR, NMR and MASS spectral methods.
4. Evaluation of newly synthesized compounds for their antihistaminic and antibacterial activity.
ENCLOSURE: II
7. .METHODOLOGY
7.1 SOURCE OF DATA:
The literature survey will be done by referring chemical abstracts of all the national and international journals pertaining to synthetic, medicinal and pharmaceutical chemistry.
The information about pharmacological and biological activities will be collected by referring Indian Journals of Medicinal Chemistry, Current Medicinal Chemistry, Bio-organicMedicinal Chemistry, Indian Journal of Pharmaceutical Science, Indian drug and Bull. Korean Chem. Soc. etc
Library of SAC College of Pharmacy, BG Nagara, Indian Institute of Science, Bangalore, IITC, Hyderabad, IIT, Chennai.
The day to day development in this area will be updated by literaturesurveythrough E-publishing and current periodicals in library of SAC College of Pharmacy, BG Nagara.
All the basic facilities required for synthetic pharmaceutical chemistry are available in laboratories of SAC College of Pharmacy. For purification of the products TLC, Column Chromatography, HPLC and other facilities such as UV, FTIR are also available in our College.
7.2 METHOD OF COLLECTION OF DATA:
The chemical structure of the synthesized compounds shall be established on the basis of physical, chemical and analytical data. Melting point of new compounds shall be determined in open capillary tube. They are expressed in degree Celsius.
The compound synthesized will be characterized by UV, IR, H1 NMR, C13 NMR and Mass spectral data. H1 NMR, C13 NMR and Mass spectra will be collected by sending the sample to other advanced research centers like IISc Bangalore, IICT Hyderabad & IIT Chennai. All the molecules will be screened for their biological activities in our laboratory.
7.3 Does the study require any investigations or interventions to be conducted on patients or animals? If so, please describe briefly.
- Yes, the antihistaminic activity will be carried out using guinea pigs ileum
7.4 Has ethical clearance been obtained from your institution in case of 7.3
- Will be obtained.
Enclosure- III
8.0 Reference:
1. Qun K. Fang, Chris H. Senanayake, H. Scott Wilkinson, Stephan A. Wild and Hui Li- “An efficient and facile synthesis of racemic and optically active fexofenadine.” Tetrahedron Letters 1998, 39; 2701-2704.
2. kawai S.H, Hambalek R.J. and Just G. - “Facile synthesis of an oxidation product of Terfenadine”. J. Org. Chem. 1994, 59; 2620-2622.
3. Sathish N.K., Karvekar M.D., Naveen H.S, Prashantha K.B.R. and Gouda M. - “Synthesis and anti-histaminic activity of fexofenadine analogues”. Indian drugs 2006,43(9); 729-732.
4. Sathish N.K., Bhagavanraju M., Hemamalini K., Gopkumar P., Narendra V. and Rajendra Prasad V.V.S. - “Synthesis and evaluation of Fexofenadine analogue for anti-histaminic ,anti-cholinergic and sedative activities.” Asian Journal of Chemistry, 19, no.6, (2007); 4809-4816.
5. Breier A.R., Nudelman N.S., Steppe M., Schapoval E.E. - “Isolation and elucidation of photodegradation product of Fexofenadine.” : J Pharm Biomed Anal, 2008 Jan 22; 46(2); 250-7.
6. Sathish N.K., Rajendra Prasad V.V.S., Karvekar M.D., Mayur Y.C., Prashantha Kumar B.R.,- “Synthesis of new Fexofenadine analogs and their pharmacological activity.” Indian Journal of heterocyclic Chemistry 2006, 16(2); 179-82.
09 /Signature of Candidate
/ (BOBADE SIDHAVINAYAK VITHALRAO)10 / Remarks of the guide / This work can be carried out in our college laboratory.
11 / Name and Designation
(In block letters)
11.1 GUIDE
Guide ship reference No. of RGUHS
11.2 Signature11.3 Head of the Department
11.4 Signature / Dr. N.K. SATHISH
M.Pharm., Ph.D.,
Professor.
Department of Pharmaceutical Chemistry,
S.A.C. College of Pharmacy,
B. G. Nagara-571448
Nagamangala(Taluk)
Mandya (Dist)
Karnataka
Dr. B.RAMESH
M. Pharm. Ph.D.,
Professor & Head,
Department of Pharmaceutical Chemistry.
S.A.C.College of Pharmacy,
B. G. Nagara-571448,
Nagamangala(Taluk),
Mandya (Dist),
Karnataka.
12 / 12.1 Remarks of the Principal
12.2 Signature
8