►
From YouTube: Open Source Antibiotics Science Update Sept 18 2020
Description
Weekly open project meeting for Open Source Antibiotics Series 2.
Full Project: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles
Relevant GitHub Issue: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles/issues/28
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (all University College London), Dr Chris Swain (Cambridge MedChem Consulting).
A
All
right
welcome
everybody,
open
source
antibiotics
series,
two
missing
on
friday
september,
the
18th.
Let
me
share
my
screen,
which
is.
A
Okay,
so
I
mean
there's
a
bunch
of
things
here
from
last
time,
which
are
the
same
so
mechanism
action
work
is
ongoing,
but
if
he
emails
back
and
forth
from
lee
graves
and
caro
wells
about
doing
that,
work
at
unc
and
they've
got
some
mercer
and
they're
doing
the
experiments.
So
it
all
looks
like
it's
going
ahead,
which
is
great.
I
think
we
should
just
check
in
on
them
in
a
week
or
so
see
how
it's
going.
A
Monash
hasn't
come
back
to
us
with
data.
I
don't
think
yet.
So
we're
still
awaiting
that
screening
for
potency
by
paul
stableton,
he
said
he's
having
to
carry
on
screening
compounds,
which
is
good
short
delay
because
terms
beginning
lots
of
teaching's
happening,
but
he's
happy
to
carry
on,
which
is
good,
and
it's
on
me
to
action.
This
thing
about
tox
screening,
which
I
think
will
be
possible
soon,
but
I
think
the
relevant
student
has
just
started
on
bio,
functionalization
and
similar
to
larry's
landscape.
A
I'm
still
waiting
on
clearance
to
talk
about
those.
So
again,
nothing
for
me
to
do
there,
but
I'll
I'll
chase
them
make
sure
we
can
talk
about.
What's
going
on
with
with
those
two
companies,
we
should
try
and
highlight
the
new
data
we've
got
because
I
think
it's
it's
exciting
that
we're
generating
compounds
and
data
and
to
highlight
the
new
compounds
that
are
coming
in
which
we'll
talk
about
in
a
second
from
ben
perry
of
dndi.
A
So
I
think
we
should
try
and
organize
a
little
tiny
micro
video
to
promote
and
promote
the
fact
that
things
are
being
contributed
still
nothing
from
bill
zurcher
about
the
original
cohort
reports,
I'll
try
one
more
time
and
then,
if
not
I'll,
just
directly
go
to
co-op
and
those
those
are
sort
of.
You
know
the
quick
things
at
the
beginning.
A
I
need
to
change
the
order
of
this
a
little
bit
to
highlight
the
big
things,
but
the
big
things
I
think
are
going
to
be
a
little
bit
of
chemistry
and
a
little
bit
about
compound
donations.
So
maybe
we
can
just
talk
about
the
compounds
incoming.
A
So
as
a
result
of
the
conversation
we
had
last
week,
which
ben
was
part
of,
he
identified
these
compounds
as
being
dnd-I
compounds
that
were
related
to
ours.
So
just
as
a
refresher,
the
I
don't
know
how
I
can
easily
make
this
okay,
it's
easier
to
see.
So
the
the
issue
we
had
last
time
was
that
these
fused
imidazole
pyridine
compounds
we
thought
were
inactive,
but
that's
because
of
course,
as
we
realized
last
time,
we
kind
of
got
the
wrong
substituent
on
the
rings.
A
So
let
me
just
let
me
just
bring
up
the
actual
thing,
so
we
can
see
the
structures
just
to
make
sure
everyone's
up
to
speed.
So
these
are
the
original
data
we
had
and
this
this
was
the
re-synthesis
compound
that
we
found
was
inactive
and
we
realized
that.
Actually,
this
part
was
then
a
problem
and
most
of
the
compounds
we
had
data
for
have
the
substituent
on
there,
including
this
imidazopyridine
compound,
which
is
the
ones
we're
just
talking
about
here,
so
including
that
core
have
the
wrong
substitution.
A
So
we
need
to
re-examine
whether
this
compound
may
be
active
and
then
was
looking
at
a
bunch
of
compounds
which
have
that
unit,
and
it's
found
all
these
compounds
that
we
can
have
evaluated
against
mercer,
so
he's
emailed
the
three
owners
of
these
compounds,
and
certainly
one
of
them,
the
biggest
supplier
ttgs
life
sciences,
have
said
that
they
are
shipping
which
is
really
good.
So
hang
on
a
second
yeah
three
units,
tcg
life
sciences
and
imperial
and
northeastern-
have
other
compounds
that
are
available
so
he's
emailed.
A
All
of
those
and
and
hopefully
shipping
will
be
incoming,
which
is
amazing,
so
dana
you're,
acting
as
recipient
for
better
or
worse
with
those
companies
and
then
paul's
happy
to
screen
him.
So
there's
a
lot
there.
Of
course
I
mean
we
are
all
data
is
good
data.
I
mean
all
of
these
share
this
feature
of
course,
and
so
we
hope
that
you
know
that
that
core
does
not
compromise
the
activity,
but
they've
all
got
the
same
two
pyridine
another
one
they've
all
got
a
two
coordinating
motif
here.
A
Well,
actually,
most
of
them
do
some
of
them
don't,
but
it's
a
nice
scatter
of
compounds
around
that
basic
chord
for
free,
which
is
really
good
and
in
the
open,
that's
absolutely
fantastic.
Hopefully
that
will
you
know,
boost
our
sar
a
bit.
A
Yeah
very
nice,
so
they'll
come
in
and
probably
get
data
on
those.
In
a
couple
of
weeks.
I
would
guess,
based
on
paul
stapleton's
availability.
A
Okay
and
then
so,
we'll
just
chase
those
those
shipments.
I
guess
the
other
thing
was
just
to
catch
up
on
the
chemistry
and
if
you
guys
wanted
to
you
got
a
slide,
you
could
share
yeah.
C
Cool
okay,
so
this
is
my
sort
of
stuff
I've
been
working
on
the
trying
to
get
the
unsubstituted
metal
core.
Well,
so
I
guess
first
of
all
I
did
make
this
dmk-136
compound
with
just
a
fennel
ring,
because
I
thought
that
that
might
turn
out
to
be.
You
know
a
useful
kind
of
baseline
compound
that
should
be
made,
so
I
just
went
ahead
and
made
that
and
then
I
got
the
certain
materials
in
for
this.
C
These
triazole
idea
that
I
had
so
I
put
this
on
the
geshira
on
last
night,
there's
still
starting
material
this
morning,
but
there's
a
couple
other
spots
on
the
tlc,
so
I
kind
of
just
kicked
the
heat
up
on
this
reaction.
I'm
gonna
check
it
tomorrow
and
then
yeah.
So
these
the
unsubstituted
or
the
mental
methyl
substituted
midazole
core.
C
The
coupling
reactions
are
a
bit
problematic.
So
this
is
just
sort
of
a
summary
of
some
things
that
I've
presented
already,
but
essentially
the
stuff
that
I've
tried.
So
putting
the
methyl
on
is
fine.
You
get
a
mixture
of
the
four
and
the
five
bromo
because
it
I
summarizes
but
they're
separable.
C
C
Those
have
been
a
bit
problematic,
so
the
latest
thing
that
I've
done
is
put
a
tozzle
on
instead
to
see,
if
maybe
the
electronics
or
the
fact
that
it's
a
little
bit
less
bulky
would
maybe
help
with
the
coupling
reactions
a
little
bit.
A
The
yeah
I
mean
this
is
the
this:
is
that
kind
of
neat
late
stage,
introduction
of
that
to
paradise.
C
A
Yeah,
I
guess
we
don't.
We
don't
have
the
microwave
in
the
lab
right,
but
the
tro
has
one.
C
A
A
C
Yeah
and
the
next
slide
is
just
sort
of
a
summary
of
the
course
that
we're
actively
pursuing
and
then
just
two
of
these
other
ideas
that
I
had,
of
course,
that
we
could
maybe
think
about
making.
But
these
I'm
going
to
kind
of
hold
off
on
until
like
until
I
can
get
the
chemistry
working
on
the
unsubstituted
imidazole.
So
I
think
it's
going
to
be
similar
chemistry.
There.
A
Okay,
yeah,
I
mean
I
also
forgot
to
mention
those
looks
really
good.
I
also
wanted
to
mention
the
so
I
guess
the
the
chemical
methodology
from
laurie.
C
C
Yeah
I
have
so
she
sent
me
their
literature,
references
and
then
the
procedure
that
they
ended
up
using
to
make
those
compounds.
C
A
I
guess
that
you
know
if
the
screen
of
these
donated
compounds
looks
promising.
Then
we
have
the
methodology
to
explore
it
quite
easily.
Yeah
yeah.
C
D
And
then
yeah,
so
for
my
stuff,
I've
just
done
a
scale-up
of
making
this
benzothyfeen
ornate
so
that
we
can
couple
it
to.
I
guess
you
know
all
the
causes
we'll
be
making.
D
I
also
thought
it
might
be
good
to
scale
up
that
oxidation
again,
because
I
guess
there
was
probably
like
10
of
that
an
oxide
product.
So
there's
like
possibly
something
else
in
there
that
I
could
fish
out,
but
yeah
a
larger
scale
would
help
with
that
and
then
so
for
all
these
ones
on
the
bottom.
The
regions
have
come
in.
So
I
got
the
three
and
four
pyridine
to
make
those
cores
so
those
I
can
do
next
week.
D
D
I
think
I've
got
them
on
the
next
slide,
but
I've
just
gotten
the
cheaper
ones.
First,
so
there's
this
pyrazine
one
and
there's
literature
procedures
to
just
brominate
that
which
is
pretty
straightforward
and
then
you
can
make
the
call
with
that,
and
then
this
was
also
pretty
cheap.
So
I
got
that
and
we
can
make
that
core
as
well
just
to
check
and
then
from
last
week.
I
think
mandrake
suggested
we
get
some
of
these
because
they
were
pretty
cheap.
D
So
I
got
this
cell
phone
methyl
cell
phone
bronic
acid
and
this
bromide,
which
I
can
just
correlate,
and
hopefully
that
is
a
bit
easier
than
like
this
kind
of
method
and
then
so.
The
other
thing
that
I've
ordered
is
this
isomar,
which
I
guess
put
through
the
same
brim,
nation
and
core
and
yeah.
I
guess
this
one
won't
have
that
to
position
nitrogen
for
like
possible
chelation
and
then
also
I
found
a
paper.
I
came
across
this
from
a
group
at
vanderbilt.
D
I
think
where
they
make
the
core
from
this
reagent,
so
the
bruminated
core,
and
then
they
did
a
suzuki
to
give
like
these
kind
of
compounds
and
then
so
I
mean
that
would
be
really
good
for
diversifying.
D
You
know
you
could
just
do
suzukis
on
both
positions
essentially
and
so
yeah
dana
suggested.
If
we
iodinate
at
the
other
position,
then
you
could
probably
do
like
successive
suzukis
at
each
position
to
get.
You
know,
lots
of
compounds
a
lot
quicker
and
I
also
found
this
core.
It's
a
bit
more
expensive,
but
it's
also
available
for
a
similar
thing.
D
So
I
don't
know
we
could
pursue
that.
I
could
buy
some
of
this
stuff
if
you
think
it's
worth
it.
A
D
D
Yeah,
so
I
think
this
step
is
pretty
good
from
the
paper
the
suzukis
give
variable
yields
from,
like,
I
guess,
10-ish
to
like
50-60,
which
I
guess
is
similar
to
our
suzuki's
anyway.
D
And
then
yeah,
so
these
ones
are
things
that
I
was
looking
for
to
substitute
like
a
lot
of
them
are
pretty
expensive,
so
I've
just
gotten
the
ones
that
are
cheap,
which
I
showed
before
so
these
ones.
Here,
I
guess,
were
from
ben's
suggestions,
I
mean
they're,
not
I
can
zoom
in
a
little
bit,
they're
not
terribly
accessible
through
our
method,
but
I
don't
know
if
this
method
works,
then
it's
probably
a
bit
easier
to
get
the
bromide
of
those,
and
what's
that.
D
D
D
A
D
Yeah,
like
I
ordered
all
those
things
like
two
days
ago
and
they
all
came
in.
A
Looks
good
to
me
so
I
mean
this.
This
has
a
lot
of
searching
you've
done
so
yeah
do
post
this,
obviously
on
the
site,
because
that's
really
useful,
as
a
record
of
all
these
things
that
we
can
get
held
off
pretty
easily.
D
D
D
A
D
Yeah
there's
a
lot
of
things.
I
think
the
first
thing
would
be
to
make
these
ones
the
three
and
four
pyridine
yeah
with
the
benzotiphane
just
to
check
those
yeah
and
then
probably
make
some
of
this
call
after
that,
and
then
yeah
we'll
see
from
there.
A
I
mean,
I
guess,
the
the
compound
that
I
posted
in
my
comment
about
the
compound
that
we
want
with
that
core,
but
with
the
benzothiaphine,
the
one,
that's
in
that's
in
the
top
of
your
slide
there,
but
with
the
fused
aromatic
ring
this
one,
no,
the
one
above
yeah,
sorry
yeah,
the
combination
of
those
two
yeah
yeah
yeah.
That's
that's
the
sort
of
high
priority
one!
Isn't
it
right?
A
Fine,
because
we
don't
have
that
in
the
in
the
in
bend,
set,
yeah,
okay,
yeah
and
then
and
then
the
three
and
four
isomers
of
the
pyridine
and
the
sulfoxide
sulfone
compounds.
B
A
Yeah
yeah.
Okay,
awesome
great,
I
think
that's
everything
there's
a
bunch
of
other
little
minor
things
on
the
on
the
github
issue,
but
we
don't
need
to
talk
about
it.
So
that's
all
good
great
nice
plan
guys
really
good.
Okay,
you
all
next
time.