Coumarin the nervous system to treat insomnia

is an oxygen containing heterocyclic compound, which plays an important role in
the realm of natural products and synthetic organic chemistry.







are plant flavonoids widely distributed in nature. Naturally occurring coumarins are found
in many plants, notably in high concentration in tonka bean, woodruff,
lavender, licorice, strawberries, apricots, cherries, cinnamon, sweet clover
and bison grass. The potent antibiotics like Novobiocin,
Coumaromycin and Chartesium are natural coumarin derivatives. The synthetic
coumarin derivatives have a wide range of biological activities against
bacteria 14, fungi 15, tumours 16, viruses 17 and HIV protease 18.
They also act as anticoagulants, free radical scavengers, lipoxygenase and
cyclooxygenase inhibitors. Furthermore the activity of coumarin depends on the
position and nature of substituent on it.

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is a naturally occurring compound containing the 4-hydroxy coumarin moiety. It
has been isolated from woodruff as well as from lavender and it is used to
prevent clotting of blood in the veins, lungs and heart. Another well-known
natural compound containing the coumarin nucleus is 7-hydroxycoumarin, also
known as umbelliferone, which is found in a variety of plants, such as carrots,
coriander, and garden angelica. It has been used as a sunscreen, a fluorescence
indicator and a dye indicator. Dicoumarol is another naturally occurring
compound containing the coumarin nucleus and is known for causing sweet clover
disease in cattle. It has been isolated from sweet clover hay and used as an
anticoagulant. The 3-aminocoumarin motif is found in a number of naturally
occurring antibiotics such as novobiocin and clorobiocin.



naturally occurring and synthetic coumarins have attracted intensive attention
from chemists due to their broad spectral properties and potential for
biological activities. Because of their wide range of application, the
preparation of coumarin and its derivatives has attracted the attention of
organic chemists.





            Pyrazoles, which are five-membered two-nitrogen-containing
heterocycles, are important organic compounds for pharmaceutical and
agrochemical industry. Numerous compounds containing pyrazole moiety are known
to exhibit antimicrobial
19, anticonvulsant 20, anticancer 21, analgesic 22, anti-inflammatory
23, anti tubercular 24, cardiovascular 25 ect.







            Structures of some biologically
important pyrazole containing drugs such as Zaleplon (1), Zoniporide (2),
Celecoxib (3), and Acomplia (4) are given below. Zaleplon (1)
affects the nervous system to treat insomnia where difficulty in falling asleep
is the primary complaint. Zoniporide (2) having a pyrazole core
structure is the selective inhibitor with the desired properties. Another
important example of biologically active pyrazole derivative is Celecoxib (3)
(the brand name Celebrex), which is the selective cycloxygenase 2 (COX 2)
inhibitor showing great promise as anti-inflammatory and analgesic agent.
Moreover, it has less undesirable side effect than the other known
anti-inflammatory agents. Acomplia (Rimonabant) (5) is the first
selective CB1 receptor blocker and has been used as an anti-obesity drug until
2009. Then, this drug was withdrawn by the European Medicines Agency because of
its side effects.



















             Benzimidazole is a heterocyclic aromatic
organic compound. This bi cyclic compound consists of the fusion of benzene and
imidazole. The most prominent benzimidazole compound in nature is N-ribosyl-dimethylbenzimidazole,
which serves as an axial ligand for cobalt in vitamin B12.

                        Benzimidazole is a white to slightly
beige solid; melting at 172 oC, boils at 360 oC, slightly
soluble in water, soluble in ethanol. It is a dicyclic compound having
imidazole ring (containing two nitrogen atoms at nonadjacent positions) fused
to benzene. Benzimidazole and its derivatives are used in organic synthesis and
vermicides or fungicides as they inhibit the action of certain microorganisms.
Examples of benzimidazole class fungicides include benomyl, carbendazim,
chlorfenazole, cypendazole, debacarb, fuberidazole, furophanate, mecarbinzid,
rabenzazole, thiabendazole, thiophanate.


are regarded as a promising class of bioactive heterocyclic compounds that
exhibit a range of biological activities like anticancer and anti-fungal 26,
anti helmintic 27, anti-inflammatory 28 and antidiabetic properties 29
ect. Benzimidazole nucleus can be termed ‘Master Key’ as it is an important
core in many compounds acting at different targets to elicit varied
pharmacological properties. Some of the drugs containing benzimidazole moiety
are given below.


















Benzimidazole derivatives are a resource for medicinal research. The knowledge
gained by various researches has suggested that substituted benzimidazoles and
heterocycles, which are the structural isosteres of nucleotides allow them to
interact easily with the biopolymers, possess pharmacological activity with
lower toxicities. Due to their enormous medicinal value, the research and
development of benzimidazole-containing drugs is an increasingly active and
attractive topic of medicinal chemistry.




belong to an important group of heterocyclic compounds containing oxygen, sulfur
and nitrogen in a five membered ring. 4-Thiazolidinones play a vital role due
to their wide range of biological activities and industrial importance.
4-Thiazolidinones are always being an attraction point for researchers because
of its efficiency towards various pharmacological usages. 




are important group of heterocyclic compounds associated with diverse
pharmacological activities such as antibacterial 30, antifungal 31,
analgesic 32, anti inflammatory 33, antitubercular 34, antimalarial 35, anti proliferative 36, anti histaminics 37, antithyroid 38, local anesthetic 39, antihelmintic 40, diural 41, and nematocidal 42.


Synthetic Routes of Thiazolidinone


methods for the preparation of 4- thiazolidinone are narrated in literature.
Some of them are described below.


1.      Cyclo
condensation of Schiff ‘bases with thiocarboxylic acid 43.



Microwave assisted synthesis of thiazolidinone
derivatives 44.


Carbodiimide mediated synthesis of
4-thiazolidinones by one-pot three-component condensation 45.


By cyclo condensation of ?-
halogenated acetanilide 46.




J. Brown, The Pyrimidines. New York: John Wiley and sons; 1962. 1-9 p.

Y. Kotaiah, N. Harikrishna, K. Nagaraju,
C. V. Rao, Synthesis and antioxidant activity of 1,3,4-oxadiazole tagged thieno2,3-dpyrimidine
derivatives, Eur. J. Med. Chem., 2012,
58, 340–345.

H. M. Aly, N. M. Saleh, H.A. Elhady,
Design and synthesis of some new thiophene, thienopyrimidine and
thienothiadiazine derivatives of antipyrine as potential antimicrobial agents, Eur. J. Med. Chem., 2011, 46, 4566–4572.

M. B. Dewal, A. S. Wani, C. Vidaillac,
D. Oupicky, M. J. Rybak, S. M. Firestine, Thieno2,3-dpyrimidinedione derivatives
as antibacterial agents, Eur. J. Med.
Chem., 2012, 51, 145–153.

S. E. Abbas, N. M. A. Gawad, R. F. George,
Y. A. Akar, Synthesis, antitumor and antibacterial activities of some novel
tetrahydrobenzo4,5thieno2,3-dpyrimidine derivatives, Eur. J. Med. Chem., 2013, 65, 195–204.

C. Y. Leung, A. M. Langille, J. Mancuso,
Y.S. Tsantrizos, Discovery of thienopyrimidine-based inhibitors of the human
farnesyl pyrophosphate synthase—parallel synthesis of analogs via a
trimethylsilylylidene intermediate, Biorg.
Med. Chem. 2013, 21, 2229–2240.

O. H. Rizk, O. G. Shaaban, I. M. El-Ashmawy,
Design, synthesis and biological evaluation of some novel thienopyrimidines and
fused thienopyrimidines as anti-inflammatory agents, Eur. J. Med. Chem. 2012, 55, 85–93.

H. M. Ashour, O. G. Shaaban, O. H. Rizk,
I. M. El-Ashmawy, Synthesis and biological evaluation of thieno 2′,3’:4,5pyrimido1,2-b1,2,4triazines
and thieno2,3-d1,2,4triazolo1,5- apyrimidines as anti-inflammatory and
analgesic agents, Eur. J. Med. Chem. 2013,
62, 341–351.

P. Bach, J. Bostrom, K. Brickmann, J.
J. J. Giezen, R. D. Groneberg, D. M. Harvey, M. O. Sullivan, F. Zetterberg, Synthesis,
structure–property relationships and pharmacokinetic evaluation of ethyl
6-aminonicotinate sulfonylureas as antagonists of the P2Y12 receptor., Eur. J. Med. Chem. 2013, 65, 360–375.

10.  J.
B. Press, J. J. McNally, J. A. Keiser, S. J. Offord, L. B. Katz, E. Giardino, R.
Falotico, A. J. Tobia, Furo3,4-dpyrimidine-2,4-dione derivatives with
antihypertensive activity. Analogues of thienopyrimidine-2,4-diones, Eur. J. Med. Chem. 1989, 24, 627–630.

11.  H. Liu, H.Q. Wang, Z.J. Liu, Bioorg. Med. Chem. Lett. 2007, 17, 2203-2209.

12.  J.C. Aponte, A.J. Vaisberg, D. Castillo,
G. Gonzalez, Y. Estevez, J. Arevalo, M. Quiliano, M. Zimic, M. Verástegui, E.
Málaga, R.H. Gilman, J.M. Bustamante, R.L. Tarleton, Y. Wang, S.G. Franzblau,
G.F. Pauli, M. Sauvain, G.B. Hammonda,
Bioorg. Med. Chem. 2010, 18, 2880-2886.

13.  H.
C. Kolb, M. G. Finn, K. B. Sharpless. Click Chemistry: Diverse Chemical
Function from a Few Good Reactions. Angew
Chem, 2001, 113, 2056-2075.

14.  S.
F. Wang, Y. Yin, X. Wu, F. Qiao, S. Sha, P. Cheng Lv, Jing Zhao, H. L. Zhu, Bioorg. Med. Chem. 2014, 22,

15.  Q.
Ji, Z. Ge, Z. Ge, K. Chen, H. Wu, X. Liu, Y. Huang, L. Yuan, X. Yang, F. Liao, Eur. J. Med. Chem. 2016, 108, 166 -176.

16.  W.
Zhang, Z. Li, M. Zhou, F. Wu, X. Hou, H. Luo, H. Liu, X. Han, G. Yan, Z. Ding,
R. Li, Bioorg. Med. Chem. Lett. 2014, 24,

17.  M. Z. Hassan, H.
Osman, M. A. Ali, M. J. Ahsan, Eur. J. Med. Chem. 2016, 123, 236-255. 

18.  T.
O. Olomola, R. Klein, N. Mautsa, Y. Sayed, P. T. Kaye, Bioorg. Med. Chem. 2013, 21, 1964–1971.

19.  S. Malladi, A.M. Isloor, S.K.
Peethambar, B.M. Ganesh, P.S.K. Goud, Synthesis and antimicrobial activity of
some new pyrazole containing cyanopyridone derivatives, Der. Pharm. Chem. 2012, 4, 43-52.

20.  M. Abdel-Aziz, G.E.A. Abuo-Rahma, A.A.
Hassan, Synthesis of novel pyrazole derivatives and evaluation of their
antidepressant and anticonvulsant activities, Eur. J. Med. Chem. 2009, 44, 3480-3487.

21.  K.M. Dawood, T.M.A. Eldebss, H.S.A.
El-Zahabi, M.H. Yousef, P. Metz, Synthesis of some new pyrazole based
1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents, Eur. J. Med. Chem. 2013, 70, 740-749.

22.  A.M. Vijesh, A.M. Isloor, P. Shetty, S.
Sundershan, H.K. Fun, New pyrazole derivatives containing 1,2,4-triazoles and
benzoxazoles as potent antimicrobial and analgesic agents, Eur. J. Med. Chem. 2013, 62, 410-415.

23.  N. Gokhan-Kelekci, S. Yabanoglu, E.
Kupeli, U. Salgin, O. Ozgen, G. Ucar, E. Yesilada, E. Kendi, A. Yesilada, A.A.
Bilgin, A new therapeutic approach in Alzheimer disease: some novel pyrazole
derivatives as dual MAO-B inhibitors and anti-inflammatory analgesics, Bioorg. Med. Chem. 2007, 15, 5775-5786.

24.  R.B. Pathak, P.T. Chovatia, H.H. Parekh,
Synthesis, antitubercular and antimicrobial evaluation of
3-(4-chlrophenyl)-4-substituted pyrazole derivatives, Bioorg. Med. Chem. Lett. 2012, 22, 5129-5133.

25.  D. Raffa, B. Maggio, M.V. Raimondi, S.
Cascioferro, F. Plescia, G. Cancemi, G. Daidone, Recent advanced in bioactive
systems containing pyrazole fused with a five membered heterocycle, Eur. J. Med. Chem. 2015, 97, 732-746.

26.  F.
Arjmand, Mohani, Bhawana, S. Ahmad, Eur.
J. Med. Chem. 2005, 40, 1103.

27.  G.
Merino, J.W. Jonker, E. Wagenaar, M.M. Pulido, A.J. Molina, A.I. Alvarez, A.H.
Schinkel, Drug Meta. Dis. 2005, 33, 614.

28.  K.C.S.
Achar, K.M. Hosamani, H.R. Seetharamareddy, Euro.
J. Med. Chem. 2010, 45, 2048.

29.  M.
Özil, M. Emirik, A. Beldüz, S. Ülker, Bioorg.
Med. Chem. 2016, 24, 5103.

30.  P.
Yashshree, S. Ankita, S. Pramod Kumar, K. Nitin, Current Pharma Res., 2011, 1, 2, 192.

31.  J.
J. Bhatt, B. R. Shah, P. B. Trivedi, N. K. Undavia, N. C. Desai, Ind. J. Chem., 1994, 33B, 189.

32.  A.
D. Taranalli, N. V. Thimmaiah, S. Srinivas, Saravanan, E. J. Pharm. Clinical Res., 2009, 2, 79.

33.  B.
Goel, T. Ram, R. Tyagi, E. Bansal, A. Kumar, D. Mukherjee, J. N. Sinha, Eur.
J. Med. Chem., 1999, 34, 265.

34.  S.
G. Kucukguzel, E. E. Oruc, S. Rollas, F. Sahin, A. Ozbek, Eur. J. Med. Chem., 2002, 37,

35.  V.
R. Solomon, W. Haq, K. Srivastava, S. K. Puri, S. B. Katti, J. Med.
Chem. 2007, 50, 394.

36.  H.
M. Faidallah, M. S. Al-Saadi, S. A. Rostom, H. T. Fahmy, Med. Chem. Res. 2007, 16, 300.

37.  M.
V. Diurno, O. Mazzoni, P. E. Calignano, F. Giordano, A. Bolognese, J. Med. Chem. 1992, 35, 2910.

38.  N.
Shah, C. K. Pant, P. C. Josh, Asian J.
Chem. 1993, 95, 83.

39.  M.
R. Choursia, Ind. J. Pharm. 1971, 33, 17.

40.  S.
K. Srivastava, R. Yadav, S. D. Srivastava, J.
Ind. Chem. Soc. 2004, 81, 342.

41.  D.
K. Raikwar, S. K. Srivastava, S. D. Srivastava, J. Ind. Chem. Soc. 2008, 85, 78.

42.  A.
Srinivas, A. Nagaraj, C. S. Reddy, J.
Heterocycl. Chem. 2008, 45, 999.

43.  K.
J. Mahta, A. C. Chawala, A. R. Parkih, Ind . J .Chem. SOC., 1979, 56(2), 173.

44.  P.
Monforte, Bioorg. Med .Chem. Letters, 2004, 11, 1793–1796.

45.  S.
Tumul, W. Haq, S. B. Katti, Tetrahedron, 2002, 58, 7619.

46.  S.
Jain, Univ. Meerut, Khurja. 2009, 21-85.


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