During an era in which Isaac Newton and Charles Darwin were making colossal
advances in physics and biology, medical therapy and drug development was still mired
in primitive, unprogressive and cruel rituals. Fortunately, by the mid 1800s times began
to change, and over the subsequent 150 years substantial progress was made. Table 3.1 lists
a number of important drug discoveries between 1842 and 2000. Although advances
were obviously being made, much of this drug discovery relied on serendipity rather
than rational drug design.
110
MEDICINAL CHEMISTRY
Table 3.1 Drug Discoveries, 1842–2000
1842
Long introduces ether as an anesthetic
1857
Locock accidentally discovers bromides as anticonvulsants
1867
Lister pioneers use of phenol as a surgical antiseptic
1869
Liebreich discovers hypnotic effects of chloral hydrate
1876
Stricker uncovers analgesic properties of salicylic acid
1882
Guthzeit and Conrad synthesize a series of barbiturates
1891
Erlich pioneers concepts of “receptor” and “chemotherapy”
1899
Meyer and Overton discover effect of lipid solubility on anesthetic action
1903
Fischer and von Mering identify hypnotic properties of barbiturates (see 1882)
1906
Hunt and Taveau synthesize and study acetylcholine
1912
Hauptmann accidentally discovers barbiturates as anticonvulsants (see 1903, 1882)
1921
Loewi demonstrates that acetylcholine is a neurotransmitter
1922
Banting and Best purify insulin as treatment for diabetes
1927
Szent-Gyorgyi isolates ascorbic acid (Vitamin C)
1929
Fleming serendipitously discovers antibacterial properties of penicillin
1932
Mietzach, Klarer, Domagk introduce first anti-streptococcal drug
1934
Ruzicka first synthesizes progesterone
1938
Merritt and Putnam use screening to identify hydantoins as anticonvulsants
1940
Chain and Florey introduce manufactured penicillin
1942
Ehrhard and Schauman produce synthetic analgesics (meperidine, methadone)
1945
Woodward and Doering synthesize quinine
1947
Lands introduces isoproterenol as a bronchodilator
1952
Charpentier identifies tricyclic phenothiazines as antipsychotics
1953
Watson and Crick deduce structure of DNA
1959
Beecham Laboratories develops semisynthetic penicillins
1959
Searle introduces the birth control pill
1960
Hoffmann-La Roche tests benzodiazepines as anxiolytics (Librium, Valium)
1962
Hansch develops principle of quantitative structure–activity relationships
1962
Pullman introduces quantum mechanics to drug design
1967
Cotzias pioneers the use of L-DOPA for treatment of Parkinson’s disease
1975
Biochemically driven rational drug design begins to flourish as method
1985
Improved computers enable computer-aided drug design to advance
1995
Advances in combinatorial chemistry advance high throughput screening
2000
Widespread use of cholinesterase inhibitors for symptomatic treatment of Alzheimer’s
disease
advances in physics and biology, medical therapy and drug development was still mired
in primitive, unprogressive and cruel rituals. Fortunately, by the mid 1800s times began
to change, and over the subsequent 150 years substantial progress was made. Table 3.1 lists
a number of important drug discoveries between 1842 and 2000. Although advances
were obviously being made, much of this drug discovery relied on serendipity rather
than rational drug design.
110
MEDICINAL CHEMISTRY
Table 3.1 Drug Discoveries, 1842–2000
1842
Long introduces ether as an anesthetic
1857
Locock accidentally discovers bromides as anticonvulsants
1867
Lister pioneers use of phenol as a surgical antiseptic
1869
Liebreich discovers hypnotic effects of chloral hydrate
1876
Stricker uncovers analgesic properties of salicylic acid
1882
Guthzeit and Conrad synthesize a series of barbiturates
1891
Erlich pioneers concepts of “receptor” and “chemotherapy”
1899
Meyer and Overton discover effect of lipid solubility on anesthetic action
1903
Fischer and von Mering identify hypnotic properties of barbiturates (see 1882)
1906
Hunt and Taveau synthesize and study acetylcholine
1912
Hauptmann accidentally discovers barbiturates as anticonvulsants (see 1903, 1882)
1921
Loewi demonstrates that acetylcholine is a neurotransmitter
1922
Banting and Best purify insulin as treatment for diabetes
1927
Szent-Gyorgyi isolates ascorbic acid (Vitamin C)
1929
Fleming serendipitously discovers antibacterial properties of penicillin
1932
Mietzach, Klarer, Domagk introduce first anti-streptococcal drug
1934
Ruzicka first synthesizes progesterone
1938
Merritt and Putnam use screening to identify hydantoins as anticonvulsants
1940
Chain and Florey introduce manufactured penicillin
1942
Ehrhard and Schauman produce synthetic analgesics (meperidine, methadone)
1945
Woodward and Doering synthesize quinine
1947
Lands introduces isoproterenol as a bronchodilator
1952
Charpentier identifies tricyclic phenothiazines as antipsychotics
1953
Watson and Crick deduce structure of DNA
1959
Beecham Laboratories develops semisynthetic penicillins
1959
Searle introduces the birth control pill
1960
Hoffmann-La Roche tests benzodiazepines as anxiolytics (Librium, Valium)
1962
Hansch develops principle of quantitative structure–activity relationships
1962
Pullman introduces quantum mechanics to drug design
1967
Cotzias pioneers the use of L-DOPA for treatment of Parkinson’s disease
1975
Biochemically driven rational drug design begins to flourish as method
1985
Improved computers enable computer-aided drug design to advance
1995
Advances in combinatorial chemistry advance high throughput screening
2000
Widespread use of cholinesterase inhibitors for symptomatic treatment of Alzheimer’s
disease