CHEMICAL STRUCTURE AND BIOLOGICAL ACTIVITY 0
An Outline Guide to Estimating Relationships
ALFRED BURGER University of Virginia, Charlottesville
MANY organic chemists would like to kuow for what biological activities a certain available or projected compound might be tested. Conversely, a pharmacologist receiving a chemical compound with an unfamiliar structure will wonder whether it may fit into s series of specific activity tests he is concerned with. The vastness of the literature of medicinal chemistry offerslittle encouragement to answering these questions, since too many compounds elicit multiple and often apparently unrelated biological effects. Neither is it possible to conclude from the presence of a given functional group that the compound will have a well-predictable activity. I n polyfunctional compounds this approach becomes extremely complicated. The present tables are to serve as a partial guide to estimating relations of chemical structures and biological activities. They can, obviously, not be complete but they contain representative examplesfor most of the better-known biological activities of drugs. The compounds are arranged according to characteristic chemical features and functional groups. This will enable both chemists and experimental biologists to classify a given compound quickly and to find probable activities of the substance. Those who ask "what types of compounds will exert a given biological action?" should consult the respective chapter of a standard text on pharmacology (1). Because of the multiple overlapping of activities attributable to certain chemical structures, reference to related structural types has been made for most compounds. Typical, often simplified or schematized structures and drugs are listed in the second and third columns of the tables. It has not been possible to include extensive and complex structural formulas for lack of space, and it may be necessary to implement these columns by referring to a medium-comprehensive text of organic chemistry (2). The biological activities listed will be self-explanatory, but again they often are rather general and do not refer to specific, carefully chosen testing procedures. The terms used may be taken as a guide to review articles describing such test procedures. Chemists not familiar with all the biological terms may wish to consult a standard medical dictionary for explanation (3). JOURNAL OF CHEMICAL EDUCATION
Polyiunotional amides
Amines Sea oiao Acids Alcohols Amides Esters Ethers Sulfonamides liress
ArCIOHl-CIRI-NHR
ArCH(NHdCH2Ar RzN(CHdnNR2 RICHO(CH~~NR?
Amino Ethers Ssc olao Amines Ethers
ROCHICHINR~
Amino Ketones See also Amines Ketones Ammonium Compounds uaternary) ee a180 Amincs Isoquinolines
Ss
Carbohydrates Sea also Alcohols Aldehydes
Hypnotioa Antloanvulaant Antibiotic Antimitotie
Stilbhmidine
Local anesthetic Try~moeidsl
Phenethylamine Ednephrine Amphetamine Serotonrn Tusminohe~tane
Pressor Vaaoconstriotoi C N S stimulant C N S effects Bronohodilator, oxytoeio Analgesic
Tripelennhmine Diphenhydrsmine Chlorprophenpyridaminc hdiphmin Methadon Pent uine Mira3 Benrooainr Dibenryline Nitrogen mustards Chioramines
Merouriale
Contain Hg
Nitro Coupounds
rNO*
Sea alao
Amines
Aoetyl?holin? Noreplnephrlnr 1:ohedrine
Cholinergie pressor C N S stimulant vasooonstriotar
Experimental nhenanthrene derivktives
Hormonal
Chlaramphenirol Nitrofuratn
Antibiotic Coaeidioidal Raoterioidal Weightreducing
..."."..-
Antimslarial
Urethans I'yrones See also Ethers
Ar.CfCOR)(CHdnNHz
Methsdon
lnhlgesio Antispasmadie
R,Nt
Tetraethylhmmaniunl Decs.methonium Aeasmethonium Neortigmine MethantlA~ne
Depressor Curareform Hypotensive , , , Cholinesterase lnh~bltory Anticholinergic Antiuloei Antiseptlo
Stilbenes
Riboflavin ATP Puromycin, Streptomyeln
Vith,"i" High-energy phosphate Anti-tumor Antibiotic
Sulfonamides Sca oiao Amides Amines slllfnn~a ~-
R(CH0H)nCHO
Analeptic Antiooasulant
Ketonic atemid.
Nitrooresols .vitrostyrenes
I.ooal anesthetic Antihirtsminics Sympatholytio Pre8sor. bion~hodilator Anti-motion slekneas
RIN+CHICHZO,CR RzNtC&CH,OCSR A r C H ~ * N ( C H ~ ) r f l o nRg)
Camphor Phenylindanediono Laotones See a1ao Add8 Aleohola lietonel
Dimethisoquine Ben~odioxanea Dibonzylrne i\lethoryph+mine Dimenhydnnate
T=OH
and
-COH
-(!OH
A m dyes Phthalein and pyronine dyes
Miorobistatio Cathartio Diagnostic
Sulfanes
A~oorbicacid Tetracycline
vitamin Antibiotic
Thioamides
Sea d m
Aminea Sulfonamides
RaSO,, ete. fHsNCaH.)%SO
RNHCSNNR'
Sulfone derivatives of 4phenybiperidine Biotin suifone
Analgeaio Vitamin sntaeoniat
Thiourea
Antithvroidd
Hydnntoina Barbiturstea Theophylline Diethvloarbamasine Suramin
Antioonvulsant Hypnotic Diuretw AntiElarial Trypanoeidal
I-Amy1 Neoatigmin oarbarnates
Local anesthetic Tumor pecrotiains Analpeaw Hyp?otio, Chollnernc Antieonvul.mt Fungistatic
DL..^,D
-.".""" Ureas
RNHCONHR'
Ureides See oiao Amides Aminea Thioureas Ethers Sea also Amines
RIO ArOR: ArOCHl
Ethyl ether Codeine Morphine Papwerine Dimethiroquine ~Meolieneaine Diohenhvdramine
Anesthetic Antitussive Analgesio Vasodilator Local &"esthetic M u d e relaxant Antihistaminic
Urethans fCsrbamatcs1 Ses olao
lmider Amin~a
Local sneathetio
ROCONHj ROCONR,
RINCS~R
Trimethadione Dithiooarbamates
TABLE 2 Biological Activities Associated with Speoial Ring Systems Binlogrcal
Ring a y s t m
DTUD piololypBS
ocli"iLie8
Indole and condensed system8
Ergvta,mine Sympatholytie Lysersm serd diethylamide Psyohotom~metio serotonin pressor Reserpine IIypotenaive, athractio
Isoquinoline
Emetine Pw~verine ,Morphine Tuboei>rarinc
Emetic, amebieidal Vasodilator Andpesic, euphorio Curareform
Phenoproparine Prometharine Chlorpromnainc
Anthelmintic Antiparkinsonism Antihisthminio Intiemetio, ataractic
Pyra~olooe
Antipmine
Antineuralgin Anakeaie
Pyrimidines a n d cond e n ~ e dsystems
Pyrimethamine
Antilnslarisl
purines. "tcridines
Caffeine, theophyuine PGA Amethopterine ii-Mereaptoyurine
Analeptic, diuretio Vitamin Antileukemia Tuinor inhibitory
Quinolinea and oondensed systema
Pamaquine Cinohophen Surfen
Antimhlarial Antiarthritio Trmanoeidal
Phenothiazine
BIBLIOGRAPHY (1) See for example: (a) DRILL, V. A., "Phennacology in Medicine,'' McGmw-Hill Book co., Inc., New York, 1954. ( 6 ) GOODMAN, L. S., and A. GILMAN,"The Pharmacalogical Bssis of Therapeutics," The Mscmilliln Go., New York. 1956. ( c ) KRANTZ, J. C., "The Pharmscologic Principles of Medical Practice," 3rd ed., Williams B Wilkins Ca., Rdtimore, 1954. (d) SOLLMANN, T. H., "A Manual a n Pharmacology and I t s Application to Therapeutics and Toxicology, 8th ed., W. R . Sanndws Co., Philadelphia, 1057. -.. .
(2) See for examplo: (a) BURGER,A,, "Medicinsl Chemistry," Interscience Publishers, Xew York, 1951, 1958. ( b ) FIESER,L. F., AND M. FIESER,"Organic Chemistry," D. C. Heath B Go., Boston, 1956. ( e ) "Merck Index of Chemicals and Drugs,'' 6th ed., Merck RT CO., Rahwa.~,N. J., 1952. (d) W~LSON, C. O., AND 0. GISVOLD,''Orgmir Chemistry in I'hnl.mnry," J. H. 1,ippinwtt Co., Philndrlphis, 1949. (3) See for csamplc: (a) UORLAND, \V. A. N., '
