Medicative Chemistry is the scientific discipline that trades with the drug find engine that provides the tools for the remainder of the organisation so they can find the importance of peculiar biological markThe chief aim of medicative chemical science is the design and find of new compounds that can be use as as drugs. Medicines are substances used to handle diseases. Drugs are molecules used as medical specialties to name, remedy, mitigate, dainty or prevent disease. This procedure involves a group of workers from assorted subdivisions such as chemical science, biological science, biochemistry, pharmacological medicine, medical specialty and computer science, etc.
The find or design of a new drug non merely requires a find or design procedure but besides the synthesis of the drug, a method of disposal, the development of trials and processs to set up how it operates in the organic structure and a safety appraisalSince antediluvian times the peoples of the universe have had a broad scope of natural merchandises that they use for medicative intents. These merchandises, obtained from animate being, vegetable and mineral beginnings, were sometimes really effectual. However, many of the merchandises were really toxic and it is interesting to observe that the Greeks used the same word pharmakon for both toxicants and medicative merchandisesAlthough many natural merchandises used in pharmaceuticals in their original chemical constructions, successful attempts have been made to better their pharmaceutic and curative belongingss by structural alterations. Some of these alterations are comparatively simple, like esterification.
Another attack to bettering curative belongingss is to place the part responsible for its biological activity and synthesise new molecules that are based on it.The first rational development of man-made drugs was carried out by Paul Ehrlich And Sacachiro Hata who produced arsphenamine in 1910 by uniting synthesis with dependable biological showing and rating processs.Heterocyclic chemical science is the chemical science subdivision covering entirely with synthesis, belongingss and application of heterocyclic compounds. Heterocyclic compound is an organic compound that contains a ring construction incorporating atom in add-on to carbon, such as S, O or N as portion of the ring. They may be either simple aromatic ring or non-aromatic rings.Hundreds of 1000 of new organic compounds are prepared yearly ad many of them entered in pharmacological screens to find the whether they have utile biological activity. The techniques of molecular artworks and computational chemical science have provided fresh chemical construction that have led to new drug.
Coumarin3 is a flavonoid discovered originally in workss. It was foremost discovered in 1820 which was obtained from Tonka bean ( Dipteyix odorata Leguminosae ) .Coumarins besides known as benzopyrons household of compounds in which benzine ring joined to pyron ring.
The derived functions of coumarin occure normally as the secondary metabolite. They present in Roots, seeds and foliages of many works species.Coumarin is found in many workss such as lavender, waldmeister, sweet trefoil and besides strawberries, cherries and cinnamon. The dietetic exposure to benzopyrone is rather important as these compounds found in many veggies, fruits, nuts, seeds, java and wine.It is estimated that mean western diet contains about 1gm/day of assorted Benzopyrans therefore it is non hard to see why extended research into their pharmacological and curative belongingss underway over many old ages. The coumarin karyon has the many diverse biological belongingss.
The natural coumarin known to hold hepatoprotective, anabolic activity. The substituted coumarins reported antimicrobic, anticancer, analgetic, anti-inflammatory, antiviral, herbicidal. They have been used as anticonvulsant, HIV Protease inhibitor, antihistaminic, ataractic and soporifics. Besides used as Fluorescent dyes, optical brighteners and every bit linear to nutrient and cosmetics.
Coumarin holding typical olfactory property like vanilla beans. It is used in the readyings of spirits and aromas.Warfarin is one of the coumarin derived functions which used as decoagulant in thrombolytic upsets.It besides used in the major surgery is occaimpanied by province called hypercoagulability4. The development of anticoagulant drugs owed its start to an probe of a disease of cowss charecerised by monolithic bleedings. When cattle eat sweet trefoil that has spoiled, the dicumarol makes the blood thin, taking ( in more terrible instance ) to internal and/or external hemorrhage. It has been besides used as rat toxicant.
Coumarin derived function besides used in the intervention of lymphedema5 Which includes loss of functional ability, Physical uncomfortableness and recurrent episodes of cellulites and lymphangitis furthermore because of loss of concentration between lymph vass and vena. specially observed in obes adult females and adult females after age 60.Coumarin related drugs are reported utile in these status. It is observed that these drugs are reduces the hurting and uncomfortableness due to lymphedeme. They have been besides reported to cut down the episodes of cellucities and lymphangitisAcquired Immunodeficiency Syndrome ( AIDS ) is a immune system degenerative disease caused by Human Immuno Virus ( HIV ) consequences in life baleful infections and malignances. Coumarin parallel has been found to potent anti HIV agentsCoumarins, an old category of compounds, are of course happening benzopyrene derived functions. A batch of coumarins have been identified from natural beginnings, particularly green workss.
The pharmacological and biochemical belongingss and curative applications of simple coumarins depend upon the form of permutation. Coumarins have attracted intense involvement in recent old ages because of their diverse pharmacological belongingss. Among these belongingss, their cytotoxic33effects were most extensively examined. In this reappraisal, their wide scope of effects on the tumours as shown by assorted in vitro and in vivo experiments and clinical surveies are discussed. Hence, these cytotoxic coumarins represent an exploitable beginning of new anticancer agents, which might besides assist turn toing side-toxicity and opposition phenomena. These natural compounds have served as valuable leads for farther design and synthesis of more active parallels.
In this reappraisal, works derived coumarins and their man-made parallels were consistently evaluated based on their works beginning, construction activity relationship and anticancer efficaciousnessCoumarins6 have been approximately categorised as follows:a ) Simple coumarins, B ) Furanocoumarins, degree Celsius ) Pyranocoumarins, vitamin D ) Biscoumarins and TriscoumarinsCHEMISTRY OF COUMARINS7Commen name: – Tonka bean camphor, coumarinlactone.Chemical name: – 2H-1-Benzopyran-2-one,2-Oxo-1,2-benzopyran, Benzopyran-2-one2H-Benzopyran-2-one.
REACTIONS OF COUMARIN:
A ) Chemical reaction WITH ELECTRIPHILIC REAGENT:1 ) Addition to carbonyl OAddition of proton to carbonyl O produces the hydroxybenzopyrelium salt.
O-Alkylation requires more powerful alkylating agent.B ) C-Substitution.In strong acidic media C-substitution of coumarin has been observed in both Rings.Bromination and chloromethylation are two illustrations of C-substitution. Bromination-rection with bromine consequences in simple add-on across heterocyclic pealing gives 3-bromocoumarin.B ) REACTION WITH NUCLEOPHILIC REAGENTA ) Hydroxides – Coumarins quantitatively hydrolysed to give salt of matching cinnamic acid ( xanthous colored liquid ) .
which is hard to insulate since acidification brings immediate relactonisation.
B ) Chemical reaction with Grignard Reagent
Coumarins react with Grignard reagent and gives mixture of merchandises ensuing from pealing gap of initial C adduct.C ) REACTION WITH REDUCING REAGENTThe hydride reagent can either respond at carbonyl C or at coupled system hence tends to bring forth the mixture.D ) CYCLOADDITIONIn Diles-Alder Reaction coumarins serves as dienophiles under coercing conditions.
SOME KNOWN DERIVATIVES OF COUMARIN8,9
SYNTHESIS OF COUMARIN
Lewis acid mediated condensation of phenol with I?-ketoesters to bring forth coumarins is called pechmann condensation
Conversion of o- hydroxyaryl ketones to chromones and coumarins with aliphatic acid anhydrides in the presence of Na salt of matching acid.
COUMARINEMPERICAL FORMULA – C6H9O2MOLECULAR WEIGHT – 146gmsPhysical FORM -White crystals, flakes or pulverizationSOLUBILITY – trichloromethane, intoxicant, ether somewhat soluble in H2O.Thaw POINT – 69 A°CBoiling POINT – 290 A°CGENERAL USES -Fixative agent in perfumerUsed as flavouring agentUsed in baccy makerUsed a flavouring agent, but it has been prohibited since 1965.PHARMACOLOGICAL OR THERAPEUTICS USESIt is a fresh Anti-coagulant such as Warfarin.
Antiadrenergic, CNS sedative.Anticancer, Antifungal, Antibacterial, take downing cholesterin degree.Diuretic, in cosmetics, respiratory stimulation.HIV-protease inhibitor
Relationship between Chemical Structure and Anticoagulant Activity40While several interesting relationships between chemical construction, physical belongingss and anticoagulant activity have been pointed out, we are still unable to specify the minimal structural features that are required to confabulate anticoagulant powers on a molecule. Following the designation of dicumarol as the agent responsible for the hemorrhagic sweet trefoil disease of cowss, legion efforts were made to modify the construction of the dicumarol molecule to bring forth decoagulants of enhanced curative value. The fact that ethyl biscoumacetate( with its low H2O solubility ) is a powerful decoagulant, while its water-soluble parent ( carboxylic acid ) is inactive,suggested that anticoagulant activity might be related, to some extent at least, to the lipotropic belongingss of the molecule.
In support of this claim they showed that simple aliphatic quintessences of 2: 2- bis- ( 4-hydroxycoumarinyl-3 ) -ethano were comparable in anticoagulant activity to dicoumarol.The work of Stahmann, Wolff & A ; T.ink demonstrated that anticoagulant activity was non confined to the bis- ( 4-hydroxycoumarin ) type of compound, but could originate in4-hydroxycoumarin itself when suited groups were substituted on C atom 3. It was found that the anticoagulant consequence increased as the chain-length of the alkyl substituent increased, and that aryl groups imparted greater activity than alkyl groups. When the ring O atom of 4-hydroxycoumarin is omitted, indane-1: 3-dione is obtained, and it has been shown that several derived functions of this substance are powerful decoagulants.In seeking a correlativity between chemical construction and pharmacological activity among decoagulants of the hydroxyconmarin and indanedione types, Mentzer ( 1948 ) postulated that the anticoagulant activity arise from the ( group I ) system present in these comp ( II ) .
The instance of 2-phenyl-2-methylindane-l: 3-dione ( III ) , which is wholly barren of any anticoagulant action, seems to back up this theory, since the presence of the methyl group prevents the happening of keto-enol tautomerism, therefore preventing the development of the system ( I ) .