Organic Chemistry

Foxglove

1208 CHAPTER 30 The Organic Chemistry of Drugs

name, a symbol, or a picture. It is in the best interest of the company to choose a name

that is easy to remember and pronounce so that when the patent expires, the public will

continue to request the drug by its proprietary name.

Each drug is also given a generic namethat any pharmaceutical company can use

to identify the product. The pharmaceutical company that develops a drug is allowed

to choose the generic name from a list of 10 names provided by an independent group.

It is in the best interest of the company to choose the generic name that is hardest to

pronounce and the least likely to be remembered, so that physicians and consumers

will continue to use the familiar proprietary name. Proprietary names must always be

capitalized, whereas generic names are not capitalized.

Drug manufacturers are permitted to patent and retain exclusive rights to the drugs

they develop. A patent is valid for 20 years. Once the patent expires, other drug com-

panies can market the drug under the generic name or under their own brand name,

which is called a branded generic name. For example, the antibiotic ampicillin is sold

as Penbritin®by the company that held the original patent. Now that the patent has ex-

pired, the drug is sold by other companies as Ampicin, Ampilar, Amplital, Binotal,

Nuvapen, Pentrex, Ultrabion, Viccillin, and 30 other branded generic names.

The over-the-counter drugs that line the shelves of drugstores are available without

prescription. They are often mixtures containing one or more active ingredients

(generic or proprietary drugs), plus sweeteners and inert fillers. For example, the

preparations called (Whitehall Laboratories), (Upjohn), and

(Bristol-Meyers Squibb) all contain ibuprofen, a mild analgesic and anti-inflammato-

ry drug. Ibuprofen was patented in Britain in 1964 by Boots, Inc., and the U.S. Food

and Drug Administration (FDA) approved its use as a nonprescription drug in 1984.

30.2 Lead Compounds

The goal of the medicinal chemist is to find compounds that have potent effects on given

diseases, with minimum side effects. In other words, a drug must react selectively with

its target and have minimal negative effects. A drug must get to the right place in the

body, at the right concentration, and at the right time. Therefore, a drug must have the ap-

propriate solubility to allow it to be transported to the target cell. If it is taken orally, the

drug must be insensitive to the acid conditions of the stomach, and it also must resist en-

zymatic degradation by the liver before it reaches its target. Finally, it must eventually be

either excreted as is or degraded to harmless compounds that can be excreted.

Medicinal agents used by humans since ancient times provided the starting point for

the development of our current arsenal of drugs. The active ingredients were isolated

from the herbs, berries, roots, and bark used in traditional medicine. Foxglove, for in-

stance, furnished digitoxin, a cardiac stimulant. The bark of the cinchona tree yielded

quinine for relief from malaria. Willow bark contains salicylates used to control fever

and pain. The sticky juice of the oriental opium poppy provided morphine for severe

pain and codeine for the control of cough. By 1882, more than 50 different herbs were

commonly used to make medicines. Many of these herbs were grown in the gardens of

religious establishments used to treat the sick.

Scientists still search the world for plants and berries and the oceans for flora and

fauna that might yield new medicinal compounds. a compound isolated from

the bark of the Pacific yew tree, is a relatively recently recognized anticancer agent

(Section 18.12).

Once a naturally occurring drug is isolated and its structure determined, it can serve as

a prototype in a search for other biologically active compounds. The prototype is called a

lead compound(i.e., a compound that plays a leading role in the search). Analogs of the

lead compound are synthesized in order to find one that might have improved therapeutic

properties or fewer side effects. The analog may have a different substituent than the lead

compound, a branched chain instead of a straight chain, or a different ring system.

Changing the structure of the lead compound is called molecular modification.

Taxol®,

Advil® Motrin® Nuprin®

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