John G. Topliss, Ph.D.


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 subsequently marketed.

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 Award.