Introduction of pharmaceutical chemistry, Summaries of Pharmaceutical Chemistry

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I N T R O D U C T I O

N TO

M E D I C I N A L

C H E M I S T R Y

2 a) History and development of medicinal chemistry b) Physicochemical properties in relation to:  (^) Biological action Ionization  (^) Solubility  (^) Partition Coefficient  (^) Hydrogen bonding  (^) Protein binding  (^) Chelation  (^) Bioisosterism  (^) Optical and Geometrical isomerism. Introduction to Medicinal Chemistry

Introduction to Medicinal Chemistry.

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History & Development of Medicinal Chemistry:

History And Development of Medicinal Chemistry:- > before thousands year ago

- She nung (Chinese emperor) made a Pharmacopoeia Chaulmoogra fruit -dysentery & diarrhoea Emetine (ipecacuanha root ) - amoebiasis Cocaine and tryptamine - hallucination >The 13th^ – 20th^ century - Chemical :analysis techniques were developed -Pharmacognosy developed -Synthesis of chemotherapeutic agent were started Kolbe (1856) synthesized – Acetic acid Berthelot (1856) synthesized – Methane Domagk stated rontosil can cure gram positive bacterial infections in human and animals.

5 Medicinal chemistry is a discipline that encloses the design, development, and synthesis of pharmaceutical drugs. The discipline combines expertise from chemistry , especially synthetic organic chemistry , pharmacology, and other biological sciences. Drugs of Antiquity (ancient time)  (^) The therapeutic plants and minerals are in use since the ancient civilization of the Chinese, the Hindus, the Mayans of Central America, and the Mediterranean people of bygone days.  (^) Shen Nung (a Chinese emperor) made a Pharmacopoeia, includind in it ch’ ang shang (an anti –malarial alkaloid ) and ma huang (from which ephedrind was isolated ).  (^) The native American Indians used chaulmooger fruit.  (^) For treating dysentery and diarrhoea, the Brazilians used emetine present in the ipecacuanha root; and it is still used in amoebiasis ancient explorers discovered that the south American Indians chewed cocaine containing coca leaves and tryptamine-containing mushoons for hallucination.  (^) Many of the developments after the 1860s arose from the synthesis of compounds specifically for their medicinal action.

History & Development of Medicinal Chemistry:

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Structure of Biological Membrane

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Physicochemical Properties in relation to Biological Action

DEFINITION:

● The ability of a chemical compound to elicit a pharmacological/ therapeutic

effect is related to the influence of various physical and chemical ( physicochemical)

properties of the chemical substance on the bio molecule that it interacts with.

1) Physical Properties

Physical property of drug is responsible for its action

2 )Chemical Properties

The drug react extracellularly according to simple chemical

reactions like neutralization, chelation, oxidation etc.

VARIOUS PHYSICO-CHEMICAL PROPERTIES ARE, ✓ (^) Solubility ✓ (^) Partition Coefficient ✓ (^) Dissociation constant ✓ (^) Hydrogen Bonding ✓ (^) Ionization of Drug ✓ (^) Redox Potential ✓ (^) Complexation ✓ (^) Surface activity ✓ (^) Protein binding ✓ (^) Isosterism

● (^) Methods to improve solubility of drugs

1. Structural modification (alter the structure of molecules)
2. Use of Cosolvents (Ethanol, sorbitol,PPG,PEG)
3. Employing surfactants
4. Complexation ● (^) Importance of solubility

1. Solubility concept is important to pharmacist because it govern the preparation of liquid dosage form and the drug must be in solution before it is absorbed by the body to produce the biological activity.
2. Drug must be in solution form to interact with receptors.

2. PARTITION CO-EFFICIENT ●Drug^ (aqueous) Drug^ (lipid) ● (^) Partition co-efficient is one of the Physicochemical parameter which influencing the drug transport & drug distribution., the way in which the drug reaches the site of action from the site of application. ● (^) Partition co-efficient is defined as equilibrium constant of drug concentration for unionized molecule in two phases. ●P[Unionize d molecule] = [drug] lipid [drug]water

● (^) Factors affecting Partition Co-efficient ➢ (^) pH ➢ (^) Co solvents ➢ (^) Surfactant ➢ (^) Complexation ● (^) Partition Co-efficient are difficult to measure in living system. ● (^) They are usually determined in vitro 1-octanol as a lipid phase and phosphate buffer of pH 7.4 as the aqueous phase. ● (^1) - octanol as a lipid phase because, ● (^) It has polar and nonpolar region ● (^) Po/w is easy to measure ● (^) Po/w often correlates with many biological properties ● (^) It can be predicted using computational mode

THE PARTITION CO-EFFICIENT, P IS DIMENSIONLESS AND ITS

LOGARITHM, LOG P IS WIDELY USED AS THE MEASURE OF LIPOPHILICITY.

• (^) The log P is measured by the following methods.

1) Shake flask method

2) Chromatographic method (HPLC)

 Phenobarbitone has a high lipid/water partition coefficient of 5.9.

 Thiopentone sodium has a chloroform/water partition coefficient of about 10 0, so

it is highly soluble in lipid.

 Hence, thiopentone sodium is used as ultra-short acting barbiturates.

● (^) IMPORTANCE OF PARTICIAN COEFFICIENT: ● (^) It is generally used in combination with the Pka to predict the distribution of drug in biological system. ● (^) The factor such as absorption, excretion & penetration of the CNS may be related to the log P value of drug. ● (^) The drug should be designed with the lowest possible ● (^) Log P, to reduce toxicity, nonspecific binding & bioavailability.

3. HYDROGEN BOND

● The hydrogen bond is a special dipole-dipole interaction between the hydrogen atom in

a polar bond such as N-H, O-H or F-H & electronegative atom O, N, F atom.

● Dipoles result from unequal sharing of electrons between atoms within a covalent

bond.

These are weak bonds and denoted as dotted lines. O-H…….O, HN-

H…….O,

● The compounds that are capable, of forming hydrogen bonding is only soluble in water.

● (^) hydrogen bonding is classified into 2 types:

1. Intermolecular

2. Intramolecular