Unit-I Introduction to Medicinal Chemistry - Medicinal Chemistry I

Content:

Introduction to Medicinal Chemistry

History and development of medicinal chemistry

Physicochemical properties in relation to biological action

Ionization, Solubility, Partition Coefficient, Hydrogen bonding, Protein binding, Chelation, Bioisosterism, Optical and Geometrical isomerism.

Drug metabolism

Drug metabolism principles- Phase I and Phase II.  Factors affecting drug metabolism including stereo chemical aspects

Introduction to Medicinal Chemistry

Medicinal chemistry is the chemistry discipline concerned with the design, development and synthesis of pharmaceutical drugs. The discipline combines expertise from chemistry and pharmacology to identify, develop and synthesize chemical agents that have a therapeutic use and to evaluate the properties of existing drugs.

History of medicinal chemistry

• The oldest records of the use of therapeutic plants and minerals are derived from the ancient civilizations of the Chinese, the Hindus, the Mayans of Central America, and the Mediterranean peoples of antiquity. The Emperor Shen Nung (2735 BC) compiled what may be called a pharmacopeia including ch’ang shang, an antimalarial alkaloid.

Quinine is an antimalarial alkaloid derived from the bark of the Cinchona tree. It was used by the Mayans to cure Malaria.

• The early explorers found that the South American Indians also chewed coca leaves (containing cocaine) and used mushrooms (containing methylated tryptamine) as hallucinogens. In ancient Greek apothecary shops, herbs such as opium, squill, and Hyoscyamus, viper toxin, and metallic drugs such as copper and zinc ores, iron sulfate, and cadmium oxide could be found. The ipecacuanha root containing emetine was used in Brazil for the treatment of dysentery.

The ipecacuanha root containing emetine was used in Brazil for the treatment of dysentery .

• The 19th Century: Age of Innovation and Chemistry The 19th century saw a great expansion in the knowledge of chemistry, which greatly extended the herbal pharmacopeia that had previously been established. Building on the work of Antoine Lavoisier, chemists throughout Europe refined and extended the techniques of chemical analysis. The synthesis of acetic acid by Adolph Kolbe in 1845 and of methane by Pierre Berthelot in 1856 set the stage for organic chemistry.

Acetic acid was synthesized by Adolph Kolbe in 1845.
Methane was synthesised by Pierre Berthelot in 1856 set the stage for organic chemistry

• The emphasis was shifted from finding new medicaments from the vast world of plants to finding the active ingredients that accounted for their pharmacologic properties. The isolation of morphine by Friedrich Sertürner in 1803, the isolation of emetine from ipecacuanha by Pierre-Joseph Pelletier in 1816, and his purification of caffeine, quinine, and colchicine in 1820 all contributed to the increased use of “pure” substances as therapeutic agents.

• The 20th Century and the Pharmaceutical Industry Diseases of protozoal and spirochetal origin responded to synthetic chemotherapeutic agents. Interest in synthetic chemicals that could inhibit the rapid reproduction of pathogenic bacteria and enable the host organism to cope with invasive bacteria was dramatically increased when the red dyestuff 2,4-diaminoazobenzene-4′-sulfonamide (Prontosil) reported by Gerhard Domagk dramatically cured dangerous systemic gram-positive bacterial infections in man and animals.
• Together with the discovery of penicillin by Alexander Fleming in 1929 and its subsequent examination by Howard Florey and Ernst Chain in 1941, led to a water-soluble powder of much higher antibacterial potency and lower toxicity than that of previously known synthetic chemotherapeutic agents. With the discovery of a variety of highly potent anti-infective agents, a significant change was introduced into medical practice. 8 The 20th Century and the Pharmaceutical Industry