Imidazole Compounds: Synthesis and Diverse Functions

INTRODUCTION

The discovery of new drug not only requires its design and synthesis but also the development of testing methods and procedure, which are needed to establish how a substance operates in the body and its suitability for use as drug. The pharmaceutical industry and in particular medicinal chemist has a continued commitment to discovery, developing and marketing new medicines or to minimize the number and magnitude of undesirable properties of already existing drugs while retaining their desirable therapeutic activity. The primary role of medicinal chemist has become to improve the existing drugs by increasing their potency and duration of action and decreasing the toxic side effects as well as creating new drug by molecular modification.

Improvement of drug efficacy can be accomplished by biological, physical or chemical means [6-7]. Of the three the highest degree of flexibility in altering drug efficacy is offered by chemical approach.

Since ancient time the people of world have had a wide range of natural product that they use for medicinal purpose.

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These products obtained from animal, vegetable & mineral sources were very effective. The early 19th century saw the extraction of pure substances from plant material. These substances were of consistent quality but only a few of the compounds isolated proved to be satisfactory as therapeutic agents. Majority of the compounds were to be toxic. The purposeful modification of the chemical structure in drug design 'the task of medicinal chemist' is also called molecular modification, chemical manipulation or molecular manipulation [8].

Procedure for drug design can be divided into following main sections.

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Search for a lead molecule

Molecular manipulation aimed at further exploitation of the leads.

Altering the molecule which in turn can change the biodistribution. Searching for structure that shows increasing specificity for the target receptor that will produce the desired pharmacological action while decreasing the affinity for undesired receptors that produce adverse responses.

Design of pharmaceutical application form.

Design of dosage regimen

The heterocyclic ring comprises the core of the active moiety or pharmacophore. By far the most numerous and most important heterocyclic systems are those of five and six membered ring. Some examples of five membered rings are the oxadiazole, triazoles, thiadiazoles, pyrazoles, pyrazolidines and imidazoles. A diversity of useful biological effects is possessed by heterocyclic compounds containing the five-membered ring like imidazole and imidazoline nucleus.

It can be inferred that the imidazole ring system itself is primarily a molecular scaffold upon which characteristic Pharmacophore for various receptors are assembled. In view of the wide spectrum of useful biological activities of imidazole compounds, it was considered worthwhile to explore synthetic pathways and biological evaluation of compounds built up on imidazole skeleton.

Since times immemorial, man has always been fighting with thediseases. To combat ill health man has been indulging in developing remedies from the state of eating fresh or dried parts of plants to the contemporary novel compounds. The conventional drugs developed from plants are not able to fill the gap, therefore it becomes imperative to synthesize certain novel drugs. In search of some novel compounds we planned the current study i.e. synthesis and biological evaluation of novel imidazole based compounds. In this work an imidazole ring structure has been selected as one of the strategies to synthesize its various derivatives which could be pharmacologically useful to living beings. In early 1950s the vital role of purines in biological systems was established and it was discovered that 5, 6-dimethyl-1-(?-D-ribofuranosyl) benzimidazole is an integral part of the structure of Vitamin B12. These findings stimulated great interest in the chemistry of imidazoles and related compounds, and considerable therapeutic as well as commercial success has been achieved.

Imidazole refers to the parent compound C3H4N2, while imidazoles are a class of heterocyclics with a similar ring structure but varying substituents. Imidazole can act as a base or as a weak acid & exists in two tautomeric forms with the hydrogen atom moving between the two nitrogens. Imidazole is a 5-membered planar ring, which is soluble in water and polar solvents. Some resonance structures of imidazole are shown below:

Figure 1

The imidazoles are a class of antifungal azole derivatives and have a broad spectrum of activity both in vitro and in vivo. The imidazole moiety is also incorporated into an important biological molecule histidine, which has an imidazole ring structure. Histidine is present in many proteins and enzymes and plays a vital role in the structure and binding functions of hemoglobin. Imidazole is a part of theophylline molecule, found in tea leaves and coffee beans, which stimulates the CNS. It is also present in anticancer drug mercaptopurine which combats leukemia by interfering with activated DNA molecule. Imidazole has been used extensively as a corrosion inhibitor on certain transition elements such as copper. The thermostable polybenzimidazole (PBI) acts as a fire retardant. The salts of imidazole have been used as ionic liquids and as precursors to stabilize carbenes.

Figure 2

A number of compounds containing imidazole moiety have found versatile role as medicinal agents for example flumizole is therapeutically important as an anti-inflammatory agent, clonidine has its medicinal importance as a potent antihypertensive drug, metronidazole finds its use as an antiprotozoal drug, cimetidine is popular for being used in ulcer patients, likewise nafimidone has established itself as an anticonvulsant drug etc. and the list of such compounds is never ending and novel compounds are being added to it each day.

Figure 3

Taking an imidazole as a lead nucleus various structural modifications can be done in its general structure, to cite, first orally active angiotensin-II receptor antagonist, Losartan (DUP-753) was designed as a very potent medicinal agent by bringing modifications to the original imidazole structure.

Figure 4

The basic moiety in losartan is imidazole nucleus. During its SAR studies it was found that chloro at 4th position and hydroxylmethyl at 5th position are not critical for binding with receptors. Therefore various semi synthetic derivatives have been designed so as to develop orally active antihypertensive compounds. Imidazole nucleus is also found in many other pharmacologically active drugs including anti-inflammatory agents and anticonlvusants etc. These findings created an enormous interest in the chemistry of imidazole and related nuclei like benzimidazole, imidazopyridine, imidazopyrdin-4-on, imidazolone and fused heterocyclic based compounds play an important role in the medicine.

A large number of therapeutic agents have been developed with the help of benzimidazole nucleus, such a compound Viz. clemizole was found to have antihistaminic activity, etonitazene was established as a potent analgesic, omeprazole was found effective in ulcerous conditions thiabendazole as an anthelmintic drugs are all well-known marketed products of imidazole series.

Thus it is evident that a large number of therapeutic agents are based on the imidazole nucleus. This heterocyclic structure provides a basic skeleton to the novel synthetic derivatives. Hence in the present work i.e. synthesis and biological evaluation of novel imidazole based compounds, we were able to synthesize about thirty derivatives and some of them have shown prominent pharmacological activity.

A large number of imidazole compounds have been synthesized and evaluated for their different biological activities. Some marketed imidazole and imidazoline nucleus containing drugs have different types of pharmacological activities. The imidazole and imidazoline based pharmaceuticals are becoming very important class of therapeutic agents and are likely to replace many obtainable organic based pharmaceuticals in the very near future. The imidazole and imidazoline based pharmaceuticals will be created on a large scale by different research development processes and will become available commercially for therapeutic uses. The biological profiles of this new generation of imidazole and imidazoline represent much progress with regard to the older compounds.

Many substituted imidazole and imidazoline derivatives possess a wide range of bioactivities such as antimicrobial, antifungal, antiviral, antiprotozoan, antimalarial, anticancer, anti-inflammatory, diuretic, muscle relaxant, antitubercular, antidepressant, anticonvulsant, acaricidal, weedicide and many other biological activities. Imidazole and imidazoline compounds are also used in preparation of various functional materials for synthetic chemistry and also present in various drugs molecules (synthetic, semisynthetic and natural). In view of growing number of applications in recent years and their bioactivity imidazole derivatives synthesis chemists and biologists in the middle of the huge increase in interest.

Imidazole is one of the most important and prosperous structures in medicinal chemistry and used in medicine as antibacterial, antifungal, anti-tuberculosis, anticancer and anti-inflammatory agents. The increased rate of resistance to ongoing antimicrobial agents inspired us to search for more effective and less toxic agents.

Antimicrobial resistance towards the drug creates a very serious problem, because of this development of resistance many drugs are useless, and the toxic effects produced by these antimicrobials are also reducing their significance. So there is a urgent need for the new antimicrobials required.

Thus, in the present study, we have reported the selective preparation of a number of condensed heterocyclic compounds as potential biological active compounds as such anti-bacterial and anti-fungal bearing imdazole ring. Amongst the heterocyclic compounds imidazole are of great interest due to the antimicrobial activities. The therapeutic importance of this nucleus prompted us to develop selective procedure of synthesis in which substituent could be arranged in a pharmacophoric pattern to display high order pharmacological activities. The aim of the present studies has been to discover some new series of compounds which, may be used as drugs based on their efficacy, lesser or no side effects and low cost involved in their preparation.

This study gets an efficient way of understanding about the target pharmacophore relationship which can further aid the process of drug design developments. This study may also accelerate the designing processes to generate a larger number of therapeutically active molecules. The molecular treatment of potentially lead molecules is still a major line of approaches for the discovery and development of new drug molecules.

Imidazole moiety have been most frequently studied, many of its analogs are active against various pathological conditions, which are discussed in brief in this article. Imidazole is an entity which has interesting physical and chemical properties, in the present article focus lies on analysis of these properties which in turn may be exploited for different pharmacological activities, like compounds having a 3,4,5-trimethoxyphenyl ring linked to either N-1 or C-4 position of the imidazole entity gave an interesting profile of cytotoxicity with specific activity against leukemia cell lines, combination of indole-imidazole compounds formed demonstrated substantial in vitro anti proliferative activities against cancer cell lines, effective substitutions are also made in the entity which resembles structures of various natural compounds whose anti cancerous activity has already been examined. Substitutions are discussed in pharmacological actions as anti neoplastic agent.

Imidazoles are less sensitive in extra intestinal parasites particularly intravascular and intestinal dwelling parasites than gastrointestinal parasites. The members of class 2-alkyl benzimidazole are believed to be the most effective ones, had been found to remove various species of nematodes and trematodes from different hosts thus various compounds had been synthesized keeping 2-alkyl benzimidazole as basic moiety.

One of the other potential activities which are studied in this article is anti inflammatory activity; amino acids are believed to be potent for any sort of inflammations or edema associated with it. Study is done in regards to develop imidazole substituents having both amino and carboxylic group. Various compounds had been developed, which are analyzed clinically to check their efficacy, a detailed review is present on such compounds, with help of peer review and published research papers.

Anti fungal activity is also been discussed, imidazole and triazoles are principal areas where substituted compounds had been developed and synthesized. Here we present some of the compounds synthesized with these moieties as their structural back bone. Thus can say imidazole is a moiety which had been exploited in the past years for synthesizing various compounds having diverse pharmacological activities, and still it can be further utilized for future prospective against various pathological conditions and other uses.

REFERANCE

  1. Wermuth CG, Ganellin CR, Lindberg P, Mitscher L.A. Eds, Annual Reports in Medicinal
  2. Chemistry, Academic press 1998, 385-395.
  3. Martin YC, Kuffer E, Austel A, Eds, Modern Drug Research, Paths to Better and safer Drugs, Marcel Dekker, Inc, New York 1989, 243-73.
  4. Rainsford K.D, Aus. J. Chem., 1975, 56, 372.
  5. Loffson T, Kaminski J J, Bodor N, J. Pharm. Sci., 1981, 70 (7), 743-749.
  6. Mishra MK, Chaturvedi P, Singh R, Singh G, Sharma LK, Pandey V, Mishra P, Council of scientific and Industrial Research National Botanical Research Institute, RanapratapMarg, Lucknow.
  7. Pelletier S.W,Alkaloids, Chemical and biological prospective, Wiley and Sons Ltd (NY); 1983.
  8. Dunston W.R., and Dymond T.S., J. Chem. Soc. 1891, 59, 410.
  9. S. B. Mhaske and N. P. Argade, The chemistry of recently isolated naturally occurring quinazolinone alkaloids, Tetrahedron,vol. 62, no. 42, pp. 9787-9826, 2006.
  10. A. K.Mahato,B. Srivastava, andS.Nithya, Chemistry structure activity relationship and biological activity of quinazoline-4(3H)-one derivatives, Inventi Rapid: Med. Chem. vol. 2, no. 1, 2011.
  11. Arora R, Kapoor A, Gill N.S, Rana A.C., Quinazolinone: an overview, IRJP, Vol. 2, Issue 12, pp. 22-28, 2011.
  12. CH.Rajveeri, D.Kumaraswamy, S.Sudharshini and B.Stephen Rathinaraj, Synthesis of some 6-bromo quinazolinone derivatives for their pharmacological activities, International Journal of Pharma and Bio Sciences, Volume 2, Issue 2010, Page No. 1-10.
  13. Division Hana, 1995, One pot synthesis of some fused quinazolines, Czech Republic, pp. 21-50.
  14. Burger A, Hansch C, Sammes PG, Taylor JB, Comprehensive Medicinal Chemistry, Pergamon press, 1, 1990.
Updated: Nov 30, 2023
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Imidazole Compounds: Synthesis and Diverse Functions. (2019, Nov 23). Retrieved from https://studymoose.com/discovery-of-new-drug-essay

Imidazole Compounds: Synthesis and Diverse Functions essay
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