Photodynamic Herbicides - Chlorophyll Biosynthesis and Technological Applications - page 369

be as good TDPH modulators as substituted 6-membered N-containing rings, and
may prove to be as good TDPH modulators as substituted 6-membered N-
containing rings to Fig. 17.3 . Chemical structures of photodynamic herbicide
templates derived from pyridine, diazine or pyrrole nuclei exhibit closure structural
similarity to tetrapyrrole quadrants. A rapid evaluation of the TDPH activity of a
few representative pyrroles confirmed our suspicions.
17.6.3.5 Search of Chemical Analogues of the Pyridine, Diazine
and Pyrrole Templates
Since the 19 TDPH templates depicted in Fig. 17.3 exhibited noticeable TDPH
activity it was conjectured that chemical analogues of these templates may also
exhibit TDPH activity. Because of limitations in man-power and the prohibitive
cost of synthesizing de novo, hundreds of TDPH template analogues, we opted for
an alternate strategy which is described below.
(a) Development of a Commercially Available Database of TDPH Analogues
A database of available TDPH template analogues was developed from commercial
sources. Commercial catalogues of organic compounds were scrutinized for all
N-containing 6 and 5-membered ring compounds. All such compounds were then
entered into a ChemBase TM database using ChemBase software. ChemBase is a
personal chemical database management system from Molecular Design Limited
(San Leandro, CA, USA). The completed database consisted of 2,118 commercially
available compounds and was used for analogue searches.
(b) Computer Search of the N-Heterocyclic Database
The computer-aided search for commercially available analogues of the TDPH
templates consisted in extracting out of the N-heterocyclic database all analogues of
the 19 templates shown in Fig. 17.3 . This was achieved by carrying substructure
searches of the database, using the 17 templates one at a time. In other words every
substructure search consisted in extracting out of the N-heterocyclic database all
analogues of that particular template. A typical template substructure search took
less than 1 min. The total search yielded 247 analogues belonging to the 17 different
templates. The chemicals were purchased from Aldrich (St Louis, MO, USA) and
were tested for TDPH activity as described below.
(c) Primary Screening of 247 Analogues for TDPH Activity
In order to determine which of the 247 TDPH template analogues were actually active
as TDPH modulators, these compounds were rapidly screened for TDPH activity.