Subject: Beginnings of QSAR, CADD?

From: "Osman F. Guner" <[email-masked]>
Date: Mon, 10 Sep 2001 08:35:51 -0700

When can be considered the starting dates of QSAR or more generally 
Computer-Aided Drug Design?

So far, there are several papers of Hansch and Fujita in the early 60's 
that are heavily cited for QSAR.  However, are there any work earlier that 
can be considered as the beginning?  How do you define the "beginning".  If 
we have to draw the line somewhere, one way of defining the "beginning" is 
the point we have transitioned from more empirical research into 
"scientific" research.  Hence, the early SAR papers may not necessarily 
qualify unless there are some statistical (or quantitative) considerations.

Given the above constraints, I had a fairly clear view of the "beginnings" 
but after starting asking around, I am not so sure anymore.  Let me share 
what I have found out so far, then I would like to hear from you of your 
opinions/suggestions.

Hugo Kubinyi proposes 1964 paper by Free and Wilson (Free-Wilson model), 
and 1964 papers by Hansch and Fujita (Hansch model).  However he also notes 
that a Bruice, Kharasch, and Winzler paper in 1956 with a first application 
of Free-Wilson type analysis.  Also a paper by Zahrandic on 1960-62 with 
Hansch-type relationships.

Yvonne Martin proposes a 1960 paper in Nature by Taylor and Wykes on MAO 
inhibitors. Another paper by Swett and Martin in 1963 involves Pargyline 
Series.

Lemont Kier proposes early 1950's with articles by Coulson (1953) and by 
the Pullmans (1955) laying out some quantitating carcinogenic activity via 
valence bond and molecular orbital computations.

Then I received a 17 page manuscript from Barbara and Marvin Charton's that 
detail the history of QSAR all the way back to 1800's.  Most of the earlier 
work were, of course, qualitative. The quantitative SAR in which the 
bioactivity is mathematically related to some set of parameters came later 
on.  The earliest mathematical formulations, according to Charton's, were 
Ferguson principle (started at 1939 but mostly at around 1950s) for 
toxicity; Hammett equation (1953); Taft equation (1956); Hansch-Fujita 
model (1962).

So... any suggestions from here on?  Are there any other references that I 
am missing?  If not, based on the above what would be your vote for the 
beginnings of CADD (note I am not limiting to QSAR alone):
1- Early 50's: [Hammett, Taft, Coulson, Pullman, Ferguson]
2- Early 60's: [Hansch-Fujita; Free-Wilson; Zahrandic; Taylor]
3- Any other suggestions?

I will be more than happy to organize and summarize the responses to the list.

Thx...osman

---
Osman F. Güner, Ph.D.
Director,  Lead Identification & Optimization
Accelrys Inc.   (858) 799-5341
[email-masked]        http://www.accelrys.com

---

From: "Dr. Richard L. Wood" <[email-masked]>
Date: Mon, 10 Sep 2001 14:15:43 -0400

Hi

I suppose that you could see Chapter 3 of the book Intermolecular Interactions
and Biomolecular
Organization by A. J. Hopfinger.  It gives a description of the development of
structure and activity
relationships as far as drug design goes.

Cheers,
Richard

--
Richard L. Wood, Ph. D.
Physical/Computational Chemist
Post-doctoral Associate
Department of Food Science
120 Stocking Hall
Cornell University, Ithaca, NY 14853