“SYNTHESES AND CHARACTERIZATION OF SOME NEW FURANS AND PYRIMIDINES FOR IN-VITRO ANTI-TUBERCULAR ACITIVITY”
SYNOPSIS FOR
M.PHARM. DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
A.RAJITHA
I M.PHARM
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
PES COLLEGE OF PHARMACY
BANGALORE-560 050
(2010-2012)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name of the candidate and address / A. RAJITHAΙ. M. PHARM
(PHARMACEUTICAL CHEMISTRY)
PES COLLEGE OF PHARMACY
HANUMANTHANAGAR
BANGALORE-560 050
PERMANENT ADDRESS:
A. RAJITHA
D/O A.SANGAPPA
NO.305,THIRD FLOOR,GVR TOWERS,NEAR RTC BUS STAND,
KADAPA-516002
ANDHRA PRADESH
2. / Name of the institution / PES COLLEGE OF PHARMACY
HANUMANTHANAGAR
B.S.K.1st STAGE
BANGALORE:-560 050
3. / Course of the study / MASTER OF PHARMACY
(PHARMACEUTICAL CHEMISTRY)
4. / Date of Admission / 19th APRIL 2010
5. / Title of the topic:
“SYNTHESES AND CHARACTERIZATION OF SOME NEW FURANS AND PYRIMIDINES FOR IN-VITRO ANTI-TUBERCULAR ACITIVITY”
The active amino group will be further derivatized with different aldehydes, acid chlorides and so on, to get the proposed title compounds.
6. / Brief resume of the intended work
6.1 Need for the study
Furans have reported to possess an assortment of pharmacological activities including anti-tubercular, antifungal, antiviral and so on. Furans also find various applications in agrochemicals and in pharmaceuticals.
Pyrimidines have reported to possess an array of pharmacological activities including anti-tubercular, analgesic, anti-pyretic, anticancer, antimicrobial, antiangiogenic and so on.
As a result of remarkable pharmacological efficacy of Furan and Pyrimidine derivatives, intensive research has been focused on anti-tubercular activity of the above mentioned nuclei.
The following are some of the Furans and Pyrimidines found to possess the above mentioned activities
6.2 REVIEW OF LITERATURE:
REFERENCES PERTAINING TO FURANS :
1. Kuntal et al ., reported the design and synthesis of (3-(benzofuran-2-yl)-5-phenyl-4,5-dihydropyrazol-1-yl)(pyridin-4-yl)carbonyl for antitubercular evaluation.(1)
2. Balasaheb Y Mane et al., reported the synthesis of 3-(phenylamino)benzofuran-2-carbohydrazide as non steroidal anti inflammatory agents.(2)
3. A convenient synthesis of 3-(benzofuran-2-yl)-1-phenyl-1H-pyrazole-carbaldehyde by Goudarshivannavar B C et al., (3)
4. Microwave assisted synthesis and antimicrobial activity of 2- (benzo-furan-2-yl)-7-(substituted) imidazo[2,1-b] benzothiazole by Rekha Rani et al., (4)
R= H
5. Rahmathullah S M et al.,reported the synthesis of 2,5-bis-(4-(N-ethoxycarbonyl-N'-isopropyl)-amidinophenyl)furan .(5)
6. Irene Drizin et al., reported the synthesis of (5-(4-chlorophenyl)furan-2-yl)(piperazin-1-yl)carbonyl for the discovery of potent furan piperazine sodium channel blockers for the treatment of neuropathic pain.(6)
7. Mollusciscidal activity of 5-amino-4-benzoyl-3-phenylfuran-2-carbonitrile was reported by Fathy M Abdelrazek et al .,(7)
8. Kristina Starcevic et al., reported the Synthesis , photochemical synthesis ,DNA binding and antitumor evaluation of Ethyl 2,8-dicyanonaphtho[2,1-b]furan-5-carboxylate.(8)
9. The synthesis of 2-(4-chlorophenyl)-3-(furan-2-ylmethyl)thiazolidin-4-one as
selective HIV-RT inhibitors was reported by Ravindra K Rawal et al.,(9)
10. Livio Racane et al., reported the synthesis of 4-(5-formylfuran-2-yl)benzoic acid.(10)
REFERENCES PERTAINING TO PYRIMIDINES :
11. Analgesic , antipyretic and DNA cleavage studies of novel pyrimidine derivatives of coumarin moiety of 4-(4-(2-amino-6-phenyl-pyrimidin-4-yl)-phenoxymethyl)-6-methyl-chromen-2-one was reported by Keri R S et al.(11)
12. Synthesis of 2-amino-6-methyl-5-(pyridin-2-ylthio)-3H-cyclopenta[d]pyrimidin- 4(7H)-one for the evaluation of their activities against human colon cancer cell lines was reported by Tangeda S J et al.,(12)
13. Jang M-Y et al., reported the synthesis of 2-bromo-7-ethoxythiazolo(4,5-d) pyrimidin-5-amine as E.coli and S. aureus secA inhibitors.(13)
14. Gangjee A et al., reported the synthesis of 6-(2,4-dichlorobenzyl)-2-amino-3H-cyclopenta[d]pyrimidin-4(7H)-one as vascular endothelial growth factor receptor-2 inhibitors and antiangiogenic and antitumor agents.(14)
15. The synthesis of 2-amino-4-(4-(dimethylamino)phenyl)-6-hydroxypyrimidine-5-carbonitrile for antibacterial activity was reported by Deshmukh MB et al., (15)
16. Gillespie R J et al., reported the synthesis of 2-amino-6-(thiazol-2-yl)pyrimidin-4-ol as antagonists of the human A2A receptors .(16)
17. Mahesh T. Chabbria et al., reported the design , synthesis and antimycobacterial activity of Ethyl 7-(methylamino)-2,3-dihydroimidazo[1,2-f]pyrimidine-8-carboxylate. (17)
18. Suryawanshi S N et al., reported the synthesis of (E)-4-hydrazinyl-6-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)pyrimidin-2-amine for the chemotherapy of leschmaniasis.(18)
19. The synthesis of 4-amino-6-(4-nitrophenyl)-2-phenylpyrimidine-5-carbonitrile for anti-inflammatory activity was reported by Emerson peter da S. et al.,(19)
20. Anu Agarwal et al., reported the synthesis of 4-(2-amino-6-(2-(2,6,6-trimethylcyclohex-2-enyl)ethyl)pyrimidin-4-yl)phenol as pregnancy interceptive agents (20).
In the view of the above findings it was thought of interest to synthesize and screen some new substituted furans and pyrimidines for invitro anti-tubercular screening. The successful scheme will be reported in the thesis.
6.3 Objectives of the study
1. To achieve the syntheses of some novel Furans and pyrimidines .
2. The purity and progress of the reactions will be monitored by micro TLC.
3. The purification of the compounds will be carried out by recrystallization using suitable solvents.
4. To characterize the structures of newly synthesized compounds by UV, IR, NMR C H N analysis and MASS spectra.
5. To evaluate the invitro antitubercular activity of the new compounds and to study the structure-activity relationships to optimize the structure.
6. To publish the research work in peer reviewed journals
7. / 7.1 Materials and methods:
Chemicals and other reagents will be purchased from standard companies. The progress of the reactions will be monitored by micro thin layer chromatography. The standard protocols will be followed for purification of the products. Structures of the synthesized molecules will be confirmed by the analytical and spectral data. The biological screening results will be used to study structure-activity relationships.
7.2 Sources of data
IISC LIBRARY, BANGALORE
PESCP LIBRARY, BANGALORE
RGUHS DIGITAL LIBRARY (Helinet)
CENTRAL COLLEGE LIBRARY, BANGALORE
7.3 Method of collection of data
Chemical Abstracts, Journals like Indian Journal of Chemistry, Journal of Medicinal Chemistry, Indian Journal of Heterocyclic Chemistry, Journal of American Chemical Society, Indian Journal of Pharmaceutical Sciences, Journal of Organic chemistry, European Journal of Medicinal Chemistry, Tetrahedron, Bioorganic & Medicinal Chemistry and Helinet.
7.4 Does the study require any investigation or interventions to be
Conducted on patients or other humans or animals?
-NO-
7.4 Has ethical clearance been obtained from your institution in
case of 7.4?
-NOT APPLICABLE-
8 / References:
1. Kuntal M, Agarwal YK. Design, synthesis and antitubercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridyl methanone and 3-benzofuran-5-aryl-1-pyrazolyl carbonyl-4-oxo-naphthyridin analogs. Eur J Med Chem. 2010;45:3831-9.
2. Balasaheb YM, Agasumundin YS, B S. Synthesis of benzofuran analogs of fenamates as nonsteroidal antiinflammatory agents. Ind J Chem. 2010;49 B:264-9.
3. Goudarshivannavar BC, Jayadevappa H, Mahadevan KM. A convenient synthesis of 2(2-benzo[b]furo)indoles and benzofuropyrazoles. Ind J Chem. 2009;48 B:1419-23.
4. Rekha Rani, Makrandi JK. Microwave assisted synthesis and antimicrobial activity of some 2-(benzo-furan-2-yl)-7-(substituted) imidazo [2,1-b] benzothiazoles. Ind JChem. 2009;48 B:1614-7.
5. Rahmathullah SM, Richard R, Jones SK. Carbamate prodrugs of N-alkyl furamidines. Eur J Med Chem. 2008;43: 174-7.
6. Irene D, Robert JG, Maraj CS, Leishi. Discovery of potent furan piperazine sodium channel blockers for the treatment of neuropathicpain. Bioorg Med Chem. 2008;16:6379-86.
7. Fathy MA, Farid AM, Sherif FE. Synthesis and molluscicidal activity of some new substituted furan and furo[2,3-d]pyrimidine derivatives. International Journal of Physical Sciences. 2007;2(8):212-6.
8. Kristina S, Marijeta K, Ivo P, Lidija S, Kresimir P, Grace KZ. Synthesis,photochemical synthesis,DNA binding and antitumor evaluation of novel cyano and amidino-substituted derivatives of naphtha furans,naphtha-thiophenes,thieno-benzofurans and their acyclic precursors. Eur J Med Chem. 2006;41:925-39.
9. Ravindra KR, Yenmandra SP, Katti SB, Declercq E. 2-(Aryl)-3-furan-2-yl methyl-thiazolidin-4-ones as selective HIV-RT Inhibitors. Bioorg Med Chem. 2005;13:6771-6.
10. Livio R, Vesna TK, David WB, Grace KZ. Synthesis of new cyano substituted bis-Benzothiazolyl Aryl furans and Aryl thiophenes. Molecules. 2003;8:342-9.
11. Keri RS, Hosamani KM, Shinglapur RV, Hugar MH. Analgesic,antipyretic and DNA cleavage studies of novel pyrimidine derivatives of coumarin moiety. Eur J Med Chem. 2010;45:2597-605.
12. Tangeda SJ, Garlapati A. Synthesis of new pyrrolo [2,3-d] pyrimidine derivatives and evaluation of their activities against human colon cancer cell lines. Eur J Med Chem. 2010;45:1453-8.
13. Jang M-Y, Jongne SD, Segers K, Anne J, Herdewijn P. Synthesis of novel 5- amino thiazolo [4,5-d] pyrimidines as E. coli and S. aureus Sec A inhibitors. Bioorg Med Chem. 2010;xxx:xxx-xxx.
14. Gangjee A, Kurup S, Ihnat MA, Thorpe JE, Shenoy SS. Synthesis and biological activity of N4- phenyl substituted-6-(2,4-dichlorophenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as vascular endothelial growth factor receptor-2 inhibitors and antiangiogenic and antitumor agents. Bioorg Med Chem. 2010;18:3575-87.
15. Deshmukh MB, Salunkhe SM, Patil DR, Anbhule PV. A novel and efficient one step synthesis of 2-amino -5-cyano-6-hydroxy-4-aryl pyrimidines and their antibacterial activitiy. Eur J Med Chem. 2009;44:2651-4.
16. Gillespie RJ, Bamford SJ, Clay A, Gaur S, Haymes T, Jackson PS, et al. Antagonists of the human A2A receptor. Part6:Further optimization of pyrimidine -4-carboxamides. Bioorg Med Chem. 2009;17:6590-605.
17. Chhabria MT, Jani MM. Design, synthesis and antimycobacterial activity of some novel imidazo[1,2-c] pyrimidines. Eur J Med Chem. 2009;44:3837-44.
18. Suryawanshi SN, Bhat BA, Pandey S, Chandra N, Gupta S. Chemotherapy of leishmaniasis. Part VII: synthesis and bioevaluation of substituted terpenyl pyrimidines. Eur J Med Chem. 2007;42:1211-7.
19. Falcao EPdS, Melo SJd, Srivatsava RM, Catanho MTJdA, Nascimento SCD. synthesis and anti-inflammatory activity of 4- amino -2-aryl-5-cyano-6-{3- and 4-(N-pthalimidophenyl)}pyrimidines. Eur J Med Chem. 2006;41:276-82.
20. Agarwal A, kumar B, Mehrotra PK, Chuhan PMS. 2,4,6-Trisubstituted pyrimidine derivatives as pregnancy interceptive agents. Bioorg Med Chem. 2005;13:1893-99.
9 / Signature of the candidate : / (A. RAJITHA)
10. / Remarks of the guide: / FORWARDED WITH REQUEST
FOR APPROVAL
11. / Name and designation of:
11.1 GUIDE
11.2 SIGNATURE /
Dr. J. Saravanan
Prof. and HOD
Department of Pharm Chemistry,
PES College of Pharmacy
Bangalore- 560 050
11.3 CO-GUIDE
11.4 SIGNATURE / ------NIL------
11.5 HEAD OF THE DEPARTMENT
11.6 SIGNATURE / Dr. J. Saravanan
Prof. and HOD
Department of Pharm Chemistry,
PES College of Pharmacy
Bangalore- 560 050
12. / 12.1 REMARKS OF THE PRINCIPAL:
12.2 SIGNATURE: Prof. Dr. S. Mohan
Principal & Director,
PES College of Pharmacy
Bangalore-560 050
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