To Synthesize New Thiophene Derivative Having Better Pharmacological Activity

To Synthesize New Thiophene Derivative Having Better Pharmacological Activity

6.0 / BRIEF RESUME OF THE INTENDED WORK
6.1 / NEED FOR THE STUDY
Thiophenes the bioisosters of benzene are of interest as pharmacodynamic molecules. The thiophene used in chemotherapy are of versatile character. Substituted thiophene can be prepared by different methods involving famous Gewald Reaction. Thiophene belongs to a family of well known heterocycles. Thiophene compounds demonstrate interesting bioactivity and many research papers have discussed the biological property, structure-activity relationship and applications in medicinal science. Several substituted thiophenes were synthesized and evaluated for their pharmacological activity1. Most of them showed anticancer, antimicrobial, antifungal, antidiabetic, anti-inflammatory, antimalarial, antiangiogenic, anti HIV PR inhibitor, antioxidant, antiamoebic, anticoagulant and they are also active against auto immune disorders.
In the present study attention has been paid to the synthesis of heterocyclic compounds bearing a thiophene moiety.
The aim of this project will be to synthesise better molecules and to test them for various pharmacological activities..
6.2 / Review of literature
Khurshid I. Molvi et al have synthesized new tetra substituted thiophene as novel anti- inflammatory agent. 1
Jose L. Gonzalez et al have described the synthesis and anti-parasitic evaluation of bis-2, 5-(4-guanivino phenyl) thiophene. 2
Bernd Peschke et al have reported Benzo(b) thiophene-2-carboxamide and benzo(b) furan-2-carboxamide as potent antagonist of human H3 receptor.3
Sarah L. Rawe et al have reported N- Glycosyl–thiophene-2-carboxamide: Effect on endothelial cell growth in presence and absence of bFGF – A significant increase in potency using per-o-acetylated sugar analogues. 4
Isabel C et al have described Evaluation of the antioxidant properties of di aryl amine in the benzo(b) thiophene series by free radicle scavenging activity and reducing power. 5
Johann Leban et al have reported Biphenyl-4-yl carbanoyl thiophene carboxylic acid as potent DHODH inhibitor.6
Sangita Sharma et al have reported the synthesis, characterization and anti- amoebic activityof copper (II) complexes with substituted thiosemi carbazones of thiophene -2- carboxaldehyde against E- histolytica.7
Laurent Brault et al have reported synthesis and biological evaluation of new thiophene analogues of kenpaullone in breast cancer cells. 8
Carlo Bonini et al have reported the synthesis, biological activity and modeling studies of two novel anti HIV PR inhibitor with a thiophene containing hydroxyl ethyl amino core.9
Sunkyung Lee et al have described 4-substituted (benzo(b) thiophene -2- carbonyl) guanidine as novel Na+/H+ exchanger isoform-1(NHE-1) inhibitors.10
Chung-Kyu Ryu et al have described the synthesis and anti-fungal activity of 5-aryl amino-4, 7-dioxobenzo (b) thiophene.11
Joseph L. Duffy et al have reported the discovery and investigation of a novel class of thiophene derived antagonist of human glucagons receptor.12
Jennifer X. Qiaoet al have reported 5-Amidino benzo(b) thiophene as dual inhibitors of factors IXa and Xa.13
Chan Mug Ahn et al have described the synthesis of symmetrical bis-alkynyl or alkyl pyridine and thiophene derivatives and their anti- angiogenic activity.14
Zhao-Kui Wan et al have reported monocyclic thiophenes as protein tyrosine phosphatase1B inhibitors: Capturing interactions with Asp48.15
6.3:- OBJECTIVE OF STUDY
The objectives of proposed study are:
  • To synthesize new thiophene derivative having better pharmacological activity
  • Charecterize the synthesized compounds by TLC, UV, IR, NMR and Mass spectroscopy.
  • To screen these newly synthesized compounds for pharmacological activity.

7.0:- Materials And Methods
7.1:- SOURCE OF DATA
Chemical abstract and other journals like European journals of medicinal chemistry, Tetrahedron , Bioorganic & Medicinal Chemistry Letters.
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.
7.3:-DOES THE STUDY REQUIRE ANY INVESTIGATION TO BE CONDUCTED ON PATIENTS OR ANIMALS?
No
7.4:-HAS ETHICAL CLEARENCE BEEN OPTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
Not Applicable.
8.0 / References:
  1. Khurshid I. Molvi, Kamala K. Vasu , Swapnil G. Yerande, Vasudevan Sudarsanam, Navedul Haque
European Journal of Medicinal Chemistry 42 (2007) 1049-1058
  1. Jose L. Gonzalez, Chad E. Stephens, Tanja Wenzler, Reto Brun, Farial A. Tanious,
W. David Wilson, Todd Barszcz, Karl A. Werbovetz, David W. Boykin.
European Journal of Medicinal Chemistry 42 (2007) 552-557
  1. Bernd Peschke, Sonja Bak, Rolf Hohlweg, Rita Nielsen, Dorthe Viuff and Karin Rimvall
Bioorganic & Medicinal Chemistry Letters 16 (2006) 3162–3165
  1. Sarah L. Rawe, Violeta Zaric, Kathy M. O Boyleb, and Paul V. Murphya,
Bioorganic & Medicinal Chemistry Letters 16 (2006) 1316–1319
  1. Isabel C. F. R. Ferreira, Maria-Joao R. P. Queiroz, Miguel Vilas-Boas,
Letı cia M. Estevinho, Agathe Begouinb, and Gilbert Kirsch
Bioorganic & Medicinal Chemistry Letters 16 (2006) 1384–1387
  1. Johann Leban, Martin Kralik, Jan Mies, Roland Baumgartner,
Michael Gassen and Stefan Tasler
Bioorganic & Medicinal Chemistry Letters 16 (2006) 267–270
  1. Sangita Sharma , Fareeda Athar, Mannar R. Maurya, Amir Azam.
European Journal of Medicinal Chemistry 40 (2005) 1414–1419
  1. Laurent Brault, Evelyne Migianu, Adrien Néguesque, Eric Battaglia,
Denyse Bagrel, Gilbert Kirsch.
European Journal of Medicinal Chemistry 40 (2005) 757–763
  1. Carlo Bonini, Lucia Chiummiento, Margherita De Bonis,Maria Funicello,
Paolo Lupattelli, Gerardina Suanno, Federico Bertib and Pietro Campanerb
Tetrahedron 61 (2005) 6580–6589
  1. Sunkyung Lee, Hyunsuk Lee,b Kyu Yang Yi, Byung Ho Lee, Sung-eun Yoo,
Kyunghee Leec and Nam Sook Chob
Bioorganic & Medicinal Chemistry Letters 15 (2005) 2998–3001
  1. Chung-Kyu Ryu, Su-Kyung Lee, Ja-Young Han, Ok-Jai Jung,
Jung Yoon Lee and Seong Hee Jeong
Bioorganic & Medicinal Chemistry Letters 15 (2005) 2617–2620
  1. Joseph L. Duffy, Brian A. Kirk, Zenon Konteatis, Elizabeth L. Campbell, Rui Liang Edward J. Brady, Mari Rios Candelore, Victor D. H. Ding, Guoqiang Jiang, Frank Liu, Sajjad A. Qureshi, Richard Saperstein, Deborah Szalkowski, Sharon Tong, Lauri M. Tota, Dan Xie, Xiaodong Yang, Peter Zafian, Song Zheng, Kevin T. Chapman, Bei B. Zhangc and James R. Tataa
Bioorganic & Medicinal Chemistry Letters 15 (2005) 1401–1405
  1. Jennifer X. Qiao, Xuhong Cheng, Dilip P. Modi, Karen A. Rossi, Joseph M. Luettgen,
Robert M. Knabb, Prabhakar K. Jadhav and Ruth R. Wexler
Bioorganic & Medicinal Chemistry Letters 15 (2005) 29–35
  1. Chan Mug Ahn, Woon-Seob Shin, Ho Bum Woo, Seokjoon Leee and Hyean-Woo Leeb Bioorganic & Medicinal Chemistry Letters 14 (2004) 3893–3896
  2. Zhao-Kui Wan, Jinbo Lee, Weixin Xu, David V. Erbe, Diane Joseph-McCarthy, Bruce C. Follows and Yan-Ling Zhang Bioorganic & Medicinal Chemistry Letters 16 (2006) 4941–4945