Dr. John G. Topliss was born near Mansfield, England in 1930.
He received a BSc degree with honors in chemistry, first class,
in 1951 from The University of Nottingham and a Ph.D. degree
in organic chemistry with Professor F. E. King on the total
synthesis of tricyclic diterpenoids from the same institution
in 1954. He then did postdoctoral research with Professor
Holger Erdtman at The Royal Technical College in Stockholm,
Sweden, on the isolation and structure determination of heartwood
constituents, and with Professor Gilbert Stork at Columbia
University on natural product total synthesis.
Dr. Topliss joined the Schering Corporation (now Schering-Plough)
as a synthetic medicinal chemist in 1957, and in the following
years worked primarily in the diuretic, antihypertensive,
CNS, and antiandrogen areas. In a roughly 10 year period he
and his research group synthesized and patented 5 drugs (trichlormethiazide,
diazoxide, halazepam, quazepam, and flutamide) which were
Seeking a more rational, theoretically based approach to analog
synthesis than was generally employed at that time, Dr. Topliss
was one of the early medicinal chemists in the pharmaceutical
industry to use quantitative structure-activity relationships
(QSAR) methodology. This led him to formulate Operational
Schemes for Analog Synthesis in Drug Design (later known as
the Topliss Tree) published in 1972, and also a related Manual
Hansch Approach published in 1977, which are simplified non-mathematical
approaches for rapidly optimizing benzene ring substitution
for potency enhancement in a compound series based on physicochemical
principles. The methodology was widely adopted by medicinal
chemists and is still in current use. It has been extensively
cited in the literature and described in many textbooks on
medicinal chemistry and specialized textbooks on drug design.
Another very significant contribution of Dr. Topliss was his
identification of the dangers of being misled by chance correlations
in quantitative structure-activity relationships which can
occur when too many variables are screened in relation to
the number of observations. He published a preliminary study
on this phenomenon in 1972 and was the first to delineate
the problem. This was important because the use of this type
of analysis was in an exponential growth phase at the time.
It was followed by a more detailed and definitive study published
in 1979 which has become a standard reference on this subject.
He also edited a book “Quantitative Structure-Activity
Relationships of Drugs” published in 1983, which provided
a comprehensive, critical account of applications of QSAR
methodology across different therapeutic areas in terms of
their contributions to medicinal chemistry.
As his career advanced Dr. Topliss became progressively more
involved with management responsibilities at Schering-Plough
and in 1975 he was appointed to the position of Senior Director
of Chemical Research. In 1979 Dr. Topliss took a new position
at Warner-Lambert/Parke-Davis as Director of Chemistry and
over the next 12 years he oversaw a large expansion of chemistry
operations. He was promoted to Vice President, Chemistry in
1983. In 1990, recognizing the potential of combinatorial
chemistry applied to the synthesis of drug-like non-peptide
compounds at a time when it was only used for peptides, he
established a group specifically devoted to this mission and
Warner-Lambert/Parke-Davis became the first pharmaceutical
company to develop and utilize such a capability (Diversomer®
technology). During the time of his leadership of Chemistry
two highly successful drugs, quinapril (Accupril®) and
atorvastatin (Lipitor®) were invented and synthesized
by chemists in the department.
In 1992 Dr. Topliss became Professor of Medicinal Chemistry
in the College of Pharmacy at The University of Michigan,
having served there as Adjunct Professor since 1983. Here
he carried out research on the prediction of drug bioavailability
resulting in the first formulation of a QSAR model for drug
human bioavailability, published in 2000, enabling in-silico
predictions of oral bioavailability in humans for unsynthesized
compounds to be made.
In the medicinal chemistry community Dr. Topliss has served
on many committees and organized various symposia sessions.
He was Program Chairman for the 1974 ACS Medicinal Chemistry
Symposium at The University of New Hampshire, Chairman of
the Gordon Conference on Quantitative Structure-Activity Relationships
in Biology in 1979, and Chairman of the Medicinal Chemistry
Gordon Conference in 1985. He was active over many years in
the Medicinal Chemistry Section of IUPAC, serving as President
from 1992-1995 and Past-President from 1996-1999.
Over his career in medicinal chemistry Dr. Topliss has authored
or co-authored some 62 papers, reviews, books and book chapters
and given 70 invited talks at scientific meetings, academic
institutions and companies throughout the world. He is also
inventor on 33 patents.
In 1986 Dr. Topliss was elected a Fellow of the American
Association for the Advancement of Science and in 1998 he
was the recipient of the ACS Division of Medicinal Chemistry