P1: PCX Printer: Yet To Come
9780521704632c07 CUFX213A/Peck 9780521618168 December 28, 2007 8:51
Section IBasic principlesMedicinal chemistry mini-dictionary
The following is not meant to be an exhaustive list of every possible chemical group
or underlying drug structure. However, it covers terms encountered most commonly.
Itis designed as a quick reference to features of drug molecules.
Acetyl:Acetyl group CH 3 COO-R (where R is a C-based group), acetic acid
(=ethanoic acid) is CH 3 COOH. A proton (H+)donor group therefore acidic and
hydrophilic. Aspirin isacetylsalicylic acid and some NSAIDs are phenylacetic
acidderivatives (e.g. diclofenac, ketoralac and indomethacin); present in the
neurotransmitteracetylcholine.Alkane:Acompound containing just carbon and hydrogen atoms (a hydrocarbon)
forming a chain of carbon atoms with fully saturated bonds. Thenormalalkanes
are unbranched and form a series starting with methane (CH 4 ), ethane
(CH 3 CH 3 ), propane (CH 3 CH 2 CH 3 ), and butane (CH 3 CH 2 CH 2 CH 3 ). Lipid-soluble,
short-chain alkanes are miscible with water.
Alkanol:Alkanes with one or more−OH substitutions. If one such substitution
occurs on a terminal C, then this is an n-alkanol (or normal alkanol). If the
substitution occurs on an inner C then this is an iso-alkanol. Presence of an−OH
increases water solubility.
Alkyl:Indicates the presence of an alkane group. Naming depends on length of
chain: 1=methyl; 2=ethyl; 3=propyl; 4=butyl; 5=pentyl; 6=hexyl; 7=
heptyl; 8=octyl; 9=nonyl; 10=decyl; 11=undecyl; 12=duodecy. The
longer the chain, the less water-soluble and more lipid-soluble. Compare the
butyl- (bupivacaine) and propyl- (ropivacaine) substitutions in the mepivacaine
local anaesthetic series.
Amide:This has an R-CO·NH 2 conformation. It is found in the chain linking the
xylidine ring with the substituted amine in amide local anaesthetics (eg.
lidocaine).
Amine:Aprimary amine group is R–NH 2 .Asecondary amine is R-NH-R′,atertiary
amine has all three H groups replaced. A monoamine contains just one amine
group in its structure. Each amino acid has one terminal with an amine group,
the other with a carboxyl group; some amino acids are monoamines, others are
diamines. Amine groups are proton acceptors and at a pH above their pKa will
become protonated and therefore carry a (+)charge. This can then increase
water solubility. Conversely, below their pKa they are more lipid soluble. A
quaternary nitrogen (sometimes misnamed a quaternary amine) is one where