Therapeutic drug analogs, humans

Medicinal chemistry has many examples of the development of successful therapeutics based on an exploration of endogenous compounds. The treatment of diabetes mellitus, for example, is based upon the administration of insulin, the hormone that is functionally deficient in this disease. The current treatment of Parkinson s disease is based upon the observation that the symptoms of Parkinson s disease arise from a deficiency of dopamine, an endogenous molecule within the human brain. Since dopamine cannot be given as a drug since it fails to cross the blood-brain barrier and enter the brain, its biosynthetic precursor, L-DOPA, has been successfully developed as an anti-Parkinson s drug. Analogously, the symptoms of Alzheimer s disease arise from a relative deficiency of acetylcholine within the brain. Current therapies for Alzheimer s-type dementia are based upon the administration of cholinesterase... 

Biologies as a class may be regulated as drugs but are defined within the Public Health Service Act [PHSA, 42 U.S.C. 262(a)] by category as a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of diseases or injuries of humans [12],... 

From the point of view of importance and chemical feasibility, chloramphenicol (Figure 9) presented an excellent subject for structural modification. It was the first truly broad-spectrum antibiotic isolated, and its structure and total synthesis were both reported two years after the discovery was announced (40, 41, 42). The synthesis of chloramphenicol analogs proved to be one of the great disappointments of early chemical research in the antibiotic field. Hundreds of analogs were synthesized, but none was found superior to the parent drug in terms either of antimicrobial activity or therapeutic index (43). The palmitate and hemisuccinate esters have provided superior dosage forms for oral and parenteral use. One synthetic analog, thiamphenicol (44) has achieved limited use in human and veterinary medicine. 

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