Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1074
Title: STUDIES ON SYNTHESIS OF SOME HETEROCYCLIC COMPOUNDS OF BIOLOGICAL IMPORTANCE
Authors: Maheshwari, Mamta
Keywords: CHEMISTRY
HETEROCYCLIC COMPOUNDS
BIOLOGICAL IMPORTANCE
MEDICINAL CHEMISTRY
Issue Date: 1979
Abstract: Investigations in medicinal chemistry largely involve the use of synthetic organic chemistry to create molecules that will alter in a useful way some disease process in a living system. Medicinal chemistry is thus a discipline which applies the principles of chemistry and biology to the creation of knowledge leading to the introduction of a new drug. Develop ment of a drug represents a balanced combination of exploratory and exploitory research activities. Recognition of structural pattern in compounds which lead to the dissociation of-the desired and undesired pharmacological actions, is often followed by the optimization of the biological activity and therapeutic index. Heterocyclic compounds are cyclic organic substances which contain in the ring system at least one atom other than carbon. The heterocyclic compounds have been extensively studied not only for their intrinsic interest but also because of their use as dyes, pesticides, plastics, herbicides, pharmaceuticals, etc. Today, developments in heterocyclic chemistry are largely made by intensive investigation of substances with pharmacologi cal potential which include their use as vitamins, hormones antibiotics, antineoplastics, central nervous system active agents, antifertility agents, etc. The study of heterocyclic compounds ia rather an observation of medicinal chemistry in 1 its broadest aspect and as such its scope is very wide. The present study, however, has been confined to a more intensive investigation of some classes of known physiologi cally active compounds. The programme of research aimed towards the development of nonsteroidal antifertility agents which can be used safely and efficaciously as oral contra ceptives, and to the syntheses of oxygen and nitrogen heterocyclic analogs of tetrahydrocannabinols, the active constituents of Cannabis satiya. Human population has grown tremendously during the last hundred years. The population bomb has made the governments throughout the world aware of the necessity for birth control as an obvious answer to overpopulation and all of its accompanying problems. For thousands of years men and women have dreamed of being abla to control fertility. Some sort of contraceptives derived from plant and other natural sources have always been used since times immemorial, which are found to be estrogenic in nature. An important stimulus to research in the area of antifertility compounds was the successful employment of progestational and progestationalestrogenic steroids in the human female. The role of critical balance of estrogens and progestagens for the maintenance of pregnancy by an interplay of hypothalamic, pituitary and ovarian function is well recognised. An interference with the level of these hormones could cause termination of pregnancy, has been an attractive basis for the designing and development of oral contraceptives. In spite of remarkable efficacy of these steroidal preparations as oral contraceptives, the method is far from ideal. They are known to produce undesirable effects characteristic to natural estrogens and progestagens and.also their continuous and complicated administration over major part of the active reproductive life of woman involves the risk of permanent disturbance of normal hormonal balance. Therefore, there is a continuing interest in the development of nonsteroidal antifertility agents, which would be effective postcoitally and would be used when needed. Although, no postcoital antifertility agent is available for clinical use, yet anumber of compounds have been shown to have antiimplantation activity in experimental animals. This provides hope that through intensive structure-activity relationship studies it would be possible to develop nonsteroidal antifertility agents which would have greater specificity for antifertility activity and possess minimized hormonal effects, The first chapter is en account of the various synthetic manipulations carried out in this direction in an attempt to prepare contraceptives which are not steroidal in nature. The syntheses of a number of 2-benzoyl-l-phenyl-, 2-(l>,2'-diphenylvinyl)-lphenylnaphtho [2,1-bj furans and 6H-naphtho Q.,2-bj furo [2, y-S\ T1"] benzopyrsn-6-ones and their basic ethers also form the subject matter of this chapter. The technique of thin layer chromatography has been increasingly used for the separation of compounds of pharmaceutical, biochemical and industrial importance. It is important because of high sensitivity and very little time and amount of the substance are needed. During the present studies, thin layer chromatography has been successfully applied for the identi fication and separation of closely related 2-benzoyl-3- phenylbenzo-, & 2-benzoyl-l-phenylnaphtho[2,l-b]furans and 2-(l' ,2'-diphenylvinyl)-3-phenylbenzo-, (%> 2-(l' ,2'-diphenylvinyl )-l-phenylnaphtho [2 ,1-bl furans and 3-hydroxy- 6H-benzo-, K naphtho[1,2-blfuro[2,3-c] [ljbenzopyran-6-ones and their basic ethers. In the lest few decades, interest in drugs which effect the mood and behaviour has increased greatly. The tranquilizing and hallucinogenic effects of some chemicals have led to believe that it is possible to control behaviour and mood of persons chemically. Hallucinogens are known to effect the central nervous system. These drugs have been reported to alter the perception of time, form, space, colour and sound, etc. Of the well known hallucinogens the cannabis preparations such as bhang, marijuana, hashish are of quite interest. The attention has, therefore, been focussed on the chemistry, pharmacology and toxicology of this drug on account of its posed danger, efficacy and potential value in clinical thereapy. The main active constituents of hemp preparations are 8 9 L - and b - tetrahydrocannabinols which causes central nervous system depression and ataxia. The most prominent effects are increased sensitivity to stimuli such as sound and touch, decreased locomotor activity, general depression, and at high doses, static and dynamic ataxia. On account of the multiple biological activities associated with cannabinoids, the # tetrahydrocannabinols have been considerably mainpulated for dissociation of biological activities. Efforts, therefore, have been made to insert nitrogen and sulfur atoms in the carbocyclic nucleus (ring C) of tetrahydrocannabinols. These compounds have shown similar biological profile with little separation of activities. The second chapter of the thesis gives a brief review of the developments in cannabinoids and discusses the synthesis of certain oxygen and nitrogen heterocyclic analogs of cannabinoids. In order to modify the biological properties of tetrahydrocannabinols, the insertion of oxygen atom appears to be quite interesting as it provides the opportunity of repeating the structural features of ring A and B i.e. the ring C is an oxygen heterocyclic fused with aromatic benzene or naphthalene ring. Therefore, the synthesis of a few 6H-naphthoQ.,2-b]furol^,3-c] C llbenzopyrans has been achieved. Dissociation of biological activities associated with a molecule can be accomplished by introducing a bonding centre in the molecule. Introduction of a nitrogen atom at the ring junction of pyran and carbocyclic rings of tetrahydrocannabinol appears to be an interesting proposition for studying the structure-activity relationship studies in this class of compounds. Thus, compounds related to cannabinoids, 7HbenzimidazoloQ., 2-c] Q-, JJbenzoxazine system, and 5Himidazolo[ l,2-cj [l,|]benzoxazine and 7H-indolo[l,2-c] [l,3ll benzoxazine derivatives have been synthesized.
URI: http://hdl.handle.net/123456789/1074
Other Identifiers: Ph.D
Appears in Collections:DOCTORAL THESES (chemistry)

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