“SYNTHESIS & EVALUATION OF SULFONYLUREAS FOR

ANTI DIABETIC ACTIVITY”

SYNOPSIS FOR

M.PHARM DISSERTATION

SUBMITTED TO

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

BY

ABHISHEK KUMAR AGRAWAL

I M.PHARM

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY,

NARGUNDCOLLEGE OF PHARMACY

BANGALORE-560085

(2008-10)

1.0 / NAME OF CANDIDATE AND ADDRESS / ABHISHEK KUMAR AGRAWAL
NargundCollege of Pharmacy,
Dattatreya nagar, II main, 100ft, BSK III Stage, Bangalore-560085.
2.0 / NAME OF THE INSTITUTION / NARGUNDCOLLEGE OF PHARMACY,
DATTATREYA NAGAR, II MAIN, 100Ft, BSK III STAGE, BANGALORE-560085.
3.0 / COURSE OF STUDY AND SUBJECT / M.PHARM
PHARMACEUTICAL CHEMISTRY
4.0 / DATE OF ADMISSION / 28th June 2008
5.0 / TITLE OF TOPIC
“SYNTHESIS & EVALUATION OF SULFONYLUREAS FOR
ANTI DIABETIC ACTIVITY”

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR P.G.

DISSERTATION

5.1 / SYSTEM OF STUDY:
SYNTHEIS OF STRUCTURAL ANALOGUE OF THE FOLLOWING MOLECULE :-

R= alkyl, heteroalkyl
Ar= aryl, heteroaryl
6.0 / BRIEF RESUME OF THE INTENDED WORK
6.1 / NEED FOR THE STUDY
A large part of the global population has complications related to hyperglycemia. We very well know that diabetes is classified into two types – Type I & Type II.
Sulfonylureas has widely been used as antidiabetic for treating type II condition. We have first generation sulfonylureas ex. Chlorpropamide, Tolbutamide .
And second generation sulfonylureasex. Glipizide, Glimepiride, Gliburide etc.
Inspite of advances in other structural classes of drugs, sulfonylureas are still widely used therapeutically for treating the clinical condition.
Given that patient suffering from Diabetes mellitus have to take drugs chronically,
Sulfonylureas has been found to be very effective with minimal side effects under long term usage.
6.2 / REVIEW OF LITERATURE
Sulfonylureas are known to have pharmacological action on insulin secreting pancreatic cells.N-aryl sulfonylureas with benzopyran substitution have been synthesized with good biological activity. [Smail Khelili et al; 2006]
Hydroxyl substituted sulfonylureas are found to have potent ATP sensitive potassium channel blocking capability as reported by Ronald & co-workers. [Ronald A.Hill et al; 2003]
Sulfonylcyanoguanidines and sulfonamidonitroethylenes are bioisosters of hypoglycemic sulfonylureas and were prepared and evaluated for their insulin release property from rat pancreatic islets. [B. Masereel et al 1997]
Bruce D. Roth & co-workers have synthesized series of sulfonylureas which have ability to inhibit the enzyme Acyl-coA:cholesterol acyltransferase (ACAT) in-vitro & in-vivo and hence form to have good hypocholesterolemic activity. [Bruce D. Roth et al; 1995]
Sulfonylureas are also found to have other biological activity as antitumor and angiotensin antagonist activity as reported into letters. [Sang-Hun Jung et al 1998] [Pierre Deprez et al 1995].
6.3:- OBJECTIVE OF STUDY
Sulfonylureas inhibit an A.T.P. dependent K+ channel in the B-cell plasma membrane and thereby initiate insulin release.[ Panten U et al, 1989]
The aim of our present study would be to synthesize sulfonylureas derivatives with suitable substituents on the Nitrogen and Sulfur.
The synthesized drug would be screened for antidiabetic activity using a suitable animal model
7.1:- SOURCE OF DATA
JOURNALS- Journal of Medicinal Chemistry, European journals of medicinal
chemistry, Indian journal of chemistry, Biochem pharmacol,
Bioorganic and Medicinal Chemistry, Bioorganic and Medicinal
Chemistry letters.
INSTITUTES-Indian Institute of Science Bangalore.
NargundCollege of Pharmacy Bangalore.
WEB-SITES-

7.2:- METHODS OF DATA COLLECTION
Chemicals and other reagents will be collected from standard companies. The reaction will be monitored by thin layer chromatography. The product will be purified by standard protocols. The separated component shall be characterized by spectroscopy. Separation, if necessary would be done by HPLC.
DURATION OF STUDY: 8 Months (June 2009-Feb2010)
Literature Survey - / Continuous process
Synthesis of Proposed Molecules – / 5 months (June 2009-Oct 2009).
Anti-diabetic Activity Determination – / 2 months (Nov 2009-Dec 2009).
Thesis Writing – / 1 months (Jan 2010-Feb 2010).
7.3:-DOES THE STUDY REQUIRE ANY INVESTIGATION TO BE CONDUCTED ON PATIENTS OR ANIMALS?
Yes
7.4:-HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
In process
8.0 / REFERENCES:
  1. Smail Khelili, Philippe Lebrun, Pascal de Tullio, Bernard Pirotte; Bioorganic & Medicinal Chemistry .2006;14: 3530-3534.
  2. Ronald A.Hill, Sonali Rudra, Bo Peng, David S. Roane, Jeffrey K. Bounds, Yang Zhang, Ahmad Adloo, Tiansheng Lu;Bioorganic & Medicinal Chemistry.2003;11:2099-2113.
  3. B. Masereel, R. Ouedraogo, J. M. Dogne, M. H. Antoine; European journal of Medicinal Chemistry.1997;32:453-456.
  4. Bruce D. Roth, W. Howard Roark, Joseph A. Picard, Richard L. Stanfield, Richard F. Bousley, Maureen K. Anderson, Katherine L. Hamelehle, Reynold Homan Brian R. Krause; Bioorganic & Medicinal Chemistry Letters.1995 ;5:2367-2370.
  5. 5. Sang-Hun Jung, Hui-Soon Lee, Jae-Shin Song, Hwan-Mook Kim, Sang-Bae Han Chang-Woo Lee,Moonsun Lee, Dong-Rack Choi, Jung-Ah Lee, Yong-Ho Chung, Sung-June Yoon, Eun-Yi Moon, Hyun-Sook Hwang, Seung-Kyoo Seong,Dug-Keun Lee; Bioorganic & Medicinal Chemistry Letters.1998;8:1547-1550.
  6. Pierre Deprez*, Bertrand Heckmann, Alain Corbier, Jean-Paul Vevert, Michel Fortin and Jacques Guillaume; Bioorganic & Medicinal Chemistry Letters.1995;5: 2605-2610.
  7. PantenU., Burgfeld J., Goerke F., Rennicke M., et al; Biochem Pharmacol.1989;38: 1217-1229.

9.0 / SIGNATURE OF THE CANDIDATE / ABHISHEK KUMAR AGRAWAL
10.0 / REMARKS OF THE GUIDE / Recommended for Dissertation work.
11.0 / NAME AND DESIGNATION OF
11.1:- GUIDE / Mr. SHANTHARAM .U
Asst. Professor
Dept. of Pharmaceutical Chemistry
NargundCollege of Pharmacy,
Bangalore-560085.
11.2:- SIGNATURE
11.3:- HEAD OF THE DEPT / Dr. L.V.G. NARGUND.
Professor and Head
Dept. of Pharmaceutical Chemistry
NargundCollege of Pharmacy,
Bangalore-560085.
11.4:- SIGNATURE
12.0 / REMARKS OF THE PRINCIPAL / Forwarded and Recommended for favorable consideration
PROF M.S.HARISH
PRINCIPAL
NARGUNDCOLLEGE OF PHARMACY
BANGALORE-560085
12.1:- SIGNATURE

1