RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name of the candidate and address / NIMAVAT BHARGAV R.
I M. PHARM(PHARMACEUTICAL CHEMISTRY)
PESCOLLEGE OF PHARMACY,
HANUMANTHANAGAR,50 FEET ROAD,
BANGALORE-560050.
PERMANENT ADDRESS:
S/O RAJESHKUMAR J. NIMAVAT
“AVADH”, AMARDHAM SOCIETY, B/H SUDAMANAGAR, KENAL KANTHA, CITY: JETPUR, DIST: RAJKOT, STATE: GUJARAT
PIN:360370
2. / Name of the institution / PESCOLLEGE OF PHARMACY
HANUMANTHANAGAR
B.S.K.1st STAGE,50 FEET ROAD,
BANGALORE-560050.
3. / Course of the study / MASTER OF PHARMACY
(PHARMACEUTICAL CHEMISTRY)
4. / Date of Admission / 05th JUNE 2009
5. / Title of the topic:
“SYNTHESES, CHARACTERIZATION AND IN-VITRO
ANTI -INFLAMMATORY AND ANTIOXIDANT ACTIVITYOF SOME NEWTHIADIAZOLES AND OXADIAZOLES”

OXADIAZOLE THIADIAZOLE
The active amino group will be further derivatized with different aldehydes, acid chloridesand so on, to get the proposed title compounds.
6. / Brief resume of the intended work
6.1 Need for the study
Thiadiazoles and Oxadiazoleshave been reported to possess an array of pharmacological properties including anti-inflammatory,analgesic, anticancer & biological activities including antibacterial, antifungal, antioxidant and so on.As a result of remarkable pharmacological efficiency of Thiadiazole and Oxadiazole derivatives, intensive research has been focused on anti-inflammatory and antioxidant activities of the above mentioned nucleus.
The following are some of the Thiadiazole and Oxadiazole derivatives found to possess some of the above mentioned activities:
Scheme: 1
1)2-phenyl-5-(6’-chloro-1’,3’-benzothiazol-2-yl-amino)-1,3,4-thiadiazole
2)4-(3’-methyl-[1”,2”,4”]-triazolo-[3’,4’-b]-[1’,3’,4’]-thiadiazol-5’-yl)aniline
3)2-(4’-methylphenyl)-5-(3”-fluorophenyl)-1,3,4-thiadiazole
4)5-(4-chlorobenzyl)-2-(p-ethoxyphenylamino)-1,3,4-thiadiazole
5)5-methyl-3-[(5’-(methylamino)-1’,3’,4’-thiadiazol-2’-yl)methyl] benzo[d]oxazol-2(3H)-one
6)2- substitutedamino-5-(2’,4’-dihydroxyphenyl)-1,3,4-thiadiazoles
7)2[(N-o-chlorobenzyl)-imidazolyl amino]-5-phenyl-1,3,4-thiadiazole
8)5-[(4’-aroyl) aryloxymethyl]-2-(4”-methylphenylamino)-1,3,4-thiadiazoles
9)2-(4’-bromobenzoylamino)-5-aryloxymethyl-1,3,4-thiadiazoles
10)2-[2’,6’,8’-trisubstituted-4’-(3H)-oxoquinazolin-3’-yl]-5-aryl-1,3,4-thiadiazoles
Scheme:2
11)5-(2’-hydroxyphenyl)-2-phenyl-1,3,4-oxadiazole
12)2-(((4’,5’-dihydro-3’-arylisoxazol-5’-yl)methoxy)methyl)-5-aryl-1,3,4-oxadiazoles
13)3,7-dimethyl-1-[(5’-aryl-1’,3’,4’-oxadiazol-2’-yl)methyl]quinoxalin-2(1H)-one
14)2-substituted-5-(methylene oxybiphenyl)-1,3,4-oxadiazoles
15)5-(2’,4’,6’-trichlorophenoxymethyl)-2-mercapto-1,3,4-oxadiazole
16)5-substituted-1,3,4-oxadiazole-2(3H)-thiones
17)2-chloro-1,4-bis-(5’-mercapto-1’,3’,4’-oxadiazol-2-ylmethyleneoxy)-phenylene
18)2-oxymethyl-[substituted phenyl]-5-phenyl-1,3,4-oxadiazoles
19)5”-phenyl-2”-[{2’,6’-dinitro-4’(1,3,4-thiadiazol-2-yl)-amino}-phenoxy methyl]-1”,3”,4”-oxadiazole
20)3-(5’-(4”-methoxyphenyl)-1’,3’,4’-oxadiazol-2’-yl)-2-phenyl-1,8-naphthyridine

1 2

3 4

5 6


910

11 12

13 14

15 16

17 18

19 20
In the view of the above observations it was thought of interest to synthesize and screen some new oxadiazoles and thiadiazoles for in-vitro anti-inflammatory and antioxidant activities. The successful scheme will be reported in the thesis.
6.2Review of the literature:
Scheme:1
Mohd A et al., reported the synthesis of pharmaceutically important 1,3,4-thiadiazole and imidazoline derivatives. These compounds showed antimicrobial activity (1)
Ibrahim DA., reported the synthesis of 3.6-disubstituted-[1,2,4]-triazolo-[3,4-b]- [1,3,4]-thiadiazole derivatives. These compounds showed anti-tumor activity (2)
John KA et al., reported the synthesis of 1,2,4-oxadiazoles, 1,3,4-oxadiazoles and 1,3,4-thiadiazoles (3)
DesaiNC et al., reported the synthesis of thiosemicarbazides, 1,2,4-triazoles, 1,3,4-thiadiazoles and 1,3,4-oxadiazoles derivatives. These compounds showed antibacterial activity (4)
Gokhan-Kelekci N et al., reported the synthesis of 1-acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones. These compounds showed analgesic, anti-inflammatory and antimicrobial activities (5)
Matysiak J et al., reported the synthesis of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. These compounds showed antiproliferative activity (6)
Servi S et al., reported the synthesis of some new methyl N-arylthiocarbamates, dimethyl N-aryldithiocarbonimidates and 2-arylamino-2-imidazolines. These compounds showed antimicrobial activity (7)
Shashikanth S et al., reported the synthesis of 5-[(4-aroyl) aryloxymethyl]-2-(4-methylphenylamino)-1,3,4-thiadiazoles and 5-[(4-aroyl) aryloxymethyl]-4-(4-methylphenyl)-3-mercapto-4H-1,2,4-triazoles. These compounds showed antimicrobial activity (8)
Zheng L et al.,reported the synthesis of 2-(4’-bromobenzoylamino)-5-aryloxymethyl-1,3,4-thiadiazoles (9)
Rama Sarma GVS et al., reported the synthesis of some new 2-[2,6,8-trisubstituted-4-(3H)-oxoquinazolin-3-yl]-5-aryl-1,3,4-thiadiazoles. These compounds showed anti-inflammatory activity (10)
Scheme:2
Shashikant RP et al., reported the synthesis of some novel substituted 1,3,4-oxadiazole and pyrazole derivatives. These compounds showed antitubercular activity (11)
Jayashankar B et al., reported the synthesis of 1,3,4-oxadiazole bearing bis(heterocycles) derivatives. These compounds showed anti-inflammatory and analgesic activities (12)
Shivananda W et al., reported the synthesis of some new 2-(3-methyl-7-substituted -2-oxoquinoxalinyl)-5-(aryl)-1,3,4-oxadiazoles. These compounds showed anti-inflammatory and analgesic activities (13)
Harish K et al., reprted the synthesis of 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid. These compounds showed anti-inflammatory and analgesic activities (14)
Mohd A et al., reported the synthesis of some 1,3,4-oxadiazole derivatives. These compounds showed anti-inflammatory activity (15)
Khalid MK et al., reported the synthesis of 5-substituted-1,3,4-oxadiazole-2(3H)-thiones. These compounds showed anti-HIV, antibacterial and antifungal activities (16)
Shivarama HB et al., reported the synthesis of 2-chloro-1,4-bis-(5-substituted 1,3,4-oxadiazol-2-ylmethoxy) phenylene derivatives. These compounds showed anticancer activity (17)
Shetgiri NP et al., reported the synthesis of oxadiazoles, phthalazines and indolinones. These compounds showed antimicrobial activity (18)
Pramilla S et al., reported the synthesis of some 5”-aryl substituted N-benzoyl methylamino-2”-[{2’,6’-dinitro-4’-(5-alkyl-1,3,4-thiadiazol-2-yl)-amino}-phenoxy methyl] incorporated-1,3,4-oxadiazoles,1”,3”,4”-oxadiazolin-5”-thiones and their mannich bases. These compounds showed antimicrobial activity (19)
Mogilaiah K et al., reported the synthesis of pyrazole and 1,3,4-oxadiazole derivatives of 2-phenyl-1,8-naphthyridine. These compounds showed antibacterial activity (20)
6.3 Objectives of the study
  1. To achieve the syntheses of some new 2-substitutedamino-5-substitutedoxadiazoles and 2-substitutedamino-5-substituted thiadiazoles.
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.
  1. To characterize the structures of newly synthesized compounds by UV, IR, NMR and MASS spectra.
  1. To evaluate thein-vitro anti-inflammatory and antioxidant activity of the newly synthesized compounds to study the structure-activity relationships and to optimize the structures.
  1. 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 in-vitro anthelmintic, anti-inflammatory and antitubercular screening results will be used to study structure-activity relationships.
7.2 Sources of data:
IISc library, Bangalore.
PESCP library, Bangalore.
RGUHS Digital library (Helinate).
CentralCollege 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, 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 ----
7.5 Has ethical clearance been obtained from your institution in case of 7.4?
----NOT APPLICABLE ----
8. / References:
  1. Mohd A, Arun K, Israr A, Khan SA. Synthesis of pharmaceutically important 1,3,4-thiadiazole and imidazolinone derivatives as antimicrobials. Ind J Chem.2009;48B:1288-93.
  2. Ibrahim DA. Synthesis and biological evaluation of 3,6-disubstituted-[1,2,4]-triazolo-[3,4-b]-[1,3,4]-thidiazole derivatives as a novel class of potential anti-tumor agents. Eur J Med Chem.2009;44:2776-81.
  3. John KA, Veeramani V, Sharmila N, Padma A, Anbarasi R. Propylphosphonic anhydride (T3P®):an efficient reagent for the one-pot synthesis of 1,2,4-oxadiazoles, 1,3,4-oxadiazoles and 1,3,4-thidiazoles. Tetrahedron.2009;65:9989-96.
  4. DesaiNC, Bhavsar AM, Shah MD, SaxenaAK. Synthesis and QSAR studies of thisemicarbazides, 1,2,4-triazoles, 1,34,-thidiazoles and 1,3,4-oxadiazoles derivatives as potential antibacterial agents. Ind J Chem.2008;47B:579-89.
  5. Gokhan-Kelekci N, Salgin-Goksen U, Goktas O, Koysal Y, Kilic E, Isik S. 1-acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones,1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: Synthesis, analgesic-anti-inflammatory and antimicrobial activities. Bioorg Med Chem Lettr.2007; 15:5738-51.
  6. Matysiak J, Opolski A. Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Bioorg Med Chem.2006;14:4483-89.
  7. Servi S, Gene M, Gur S, Koca M. Synthesis and antimicrobial activity of some new methyl-N-arylthiocarbamates, dimethyl-N-aryldithio-carbonimi-dates and 2-arylamino-2-imidazolines. Eur J Med Chem.2005;40:687-93.
  8. Shashikanth S, Sudha BS, Khanum SA. Synthesis and antimicrobial activity of 5-[(4-aroyl)aryloxymethyl]-2-(4-methylphenylamino)-1,3,4-thidiazoles and 5-[(4-aroyl)aryloxymethyl]-4-(4-methylphenyl)-3-mercapto-4H-1,2,4-triazoles. Ind J Chem.2003;42B:2652-56.
  9. Zheng L, Wang X, Da Y, Chen J. Synthesis of 2-(4’-bromobenzoylamino)-5-aryloxymethyl-1,3,4-thidiazoles. Ind J Chem.2001;40B:422-25.
  10. Rama Sarma GVS, Kumar MS. Synthesis of some new 2-[2,6,8-trisubstituted-4(3H)-oxoquinazolin-3-yl]-5-aryl-1,3,4-thidiazoles as potential anti-inflammatory agents. Ind J Heterocycl Chem.1998;7:281-84.
  1. Shashikant RP, Rabara PA, Jayshri SP, Bukitagar AA, Wakale VS, Musmade DS. Synthesis and evaluation of some novel substituted 1,3,4-oxadiazole and Pyrazole derivatives for antitubercular activity. Ind J Chem.2009;48B:1453-56.
  2. Jayashankar B, Lokanath KM, Baskaran N, Sathish HS. Synthesis and pharmacological evaluation of 1,3,4-oxadiazole bearing bis(heterocycle)derivatives as anti-inflammatory and analgesic agents. Eur J Med Chem.2009;44:3898-3902.
  3. Shivananda W, AirodyVA, Nalilu SK. Synthesis of some new 2-(3-methyl-7-substituted-2-oxoquinoxalinyl)-5-(aryl)-1,3,4-oxadiazoles as potential non-steroidal anti-inflammatory and analgesic agents. Ind J Chem.2008;47B:439-48.
  4. Harish K, Sadique AJ, Suroor AK, Mohd A. Synthesis of 1,3,4-oxadiazole/thidiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid and their preliminary evaluation of biological properties. Eur J Med Chem.2008;43:1-11.
  5. Mohd A, Javed SA, Harish K. Synthesis of some 1,3,4-oxadiazole derivatives as potential anti-inflammatory agents. Ind J Chem.2007;46B:1014-19.
  6. Khalid MK, Sohail AS, Mubeen R, Muhammad A, Shahnaz P, Awais A and Wolfong V. Synthesis of 5-substituted-1,3,4-oxadiazole-2(3H)-thiones as anti-HIV, antibacterial or antifungal agents. Letters in Org Chem.2006; 3:286-88.
  7. Shivarama HB, Narayana PK. Subrahmanya BK, Mithun A, Boja P. Synthesis of 2-chloro-1,4-bis-(5-substituted-1,3,4-oxadiazole-2-ylmethoxy) phenylene derivatives as anticancer agents. Ind J Chem.2005;44B:1669-73.
  8. Shetgiri NP, Nayak BK. Synthesis of oxadiazoles, phthalazines and indolinones as antimicrobial agents. Ind J Chem.2005;44B:1267-72.
  9. Pramilla S, Vartika R, Garg SP. Synthesis of some 5”-aryl substituted/N-benzoyl methylamino-2”-[{2’,6’-dinitro-4’(5-alkyl-1,3,4-thiadiazol-2-yl)-amino}-phenoxymethyl] incorporated-1,3,4-oxadiazoles, 1”,3”,4”-oxadiazolin-5”-thiones and their mannich bases as antimicrobial agents. Ind J Heterocycl Chem.2003;12:301-06.
  10. Mogilaiah K, Srinivasa CD, Babu RR, Bennur SC. Synthesis of Pyrazole and 1,3,4-oxadiazole derivatives of 2-phenyl-1,8-naphthyridine as antibacterial agents. Ind J Chem.2001;40B:43-48.