►
From YouTube: Open Source Antibiotics Science Update Sept 4 2020
Description
Weekly open project meeting for Open Source Antibiotics Series 2.
Full Project: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles
Relevant page: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles/issues/24
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (all University College London), Dr Chris Swain (Cambridge MedChem Consulting)
A
Welcome
everybody
to
open
source
antibiotics
series
to
friday
september
the
4th
I
will
now
share
screen
so
that
I
can
just
highlight.
A
Yeah,
so
the
idea
here
is
to
work
through
this
agenda
thanks
for
putting
this
up
here
there.
Now
we
can
just
work
through
the
various
things
here.
So
I
mean,
I
guess,
just
taking
a
step
back.
A
The
the
project
is
at
the
point
where
you
know
chemistry's
started
so
ed
and
dana
have
been
doing
a
bunch
of
molecule
synthesis
and
we
need
to
get
those
evaluated
to
see
what
changes
we're
making
and
we're
trying
to
push
on
both
of
the
mechanisms
of
action
stuff
and
the
metabolic
clearance
side
of
this
project.
Those
are
the
three
main
aims:
sar
clearance
and
mechanism
of
action,
and
we
we
have
to
give
an
update
to
our
funders
by
the
end
of
september.
A
That's
not
the
final
end,
but
you
know
we
have
to
give
an
update
as
soon
as
we
can
and
yeah.
I
think
once
we
send
some
compounds
for
evaluation
for
potency
it'll
be
a
little
bit
of
a
delay.
While
we
sort
of
work
out
what
the
results
are
and
we
need
to
take
on
board
the
results
from
monash
and
then
we
can
do
better
design
for
the
second
phase,
so
we'll
go
in
fits
and
start,
but
we're
at
a
particularly
productive
period.
At
the
moment,
I
think
we're
getting
everything
going.
A
The
aim
here
with
the
project
is
there
is
not
a
full.
You
know
full
year-long
research
project.
The
aim
here
is
to
get
just
enough
data
that
we
can
make
a
decision
on
whether
to
go
for
follow-up
funding.
A
A
So
mechanism
of
action,
stuff,
yeah
lee
graves
at
unc-
is
the
guy
who's
going
to
be
doing
the
relevant
experiments
which
have
been
talked
about
previously
and
he
wrote
today
that
he's
ready
to
go
so
the
sort
of
I
think
the
action
artist
is
done,
but
he's
going
to
do
these,
they
will
now
do,
and
maybe
we
can
chase
this
in
a
couple
of
weeks.
Let's
say
because
he
said
he
was
going
to
get
going
with
those
which
is
good.
A
All
the
compounds
he
needs
are,
I
think,
at
chapel
hill
already.
So
that's
good
for
the
monash
measurement
of
injury,
vitro
pk.
We
have
done
all
the
shipping.
I
think
we've
completely
finished
right
now.
I
mean
it's
all
done
right,
so
yeah.
A
Of
the
compounds
are
available
solids,
but
not
one
of
the
key
ones
and
ed
shipped
that
all
right
great.
We
can
get
rid
of
all
this,
so
this
is
now
complete
and
we're
awaiting
the
data.
That's
it
which
is
good.
So
we
don't
need
to
do
anything
about
that.
I'm
sure
those
data
will
come
through
without
us
chasing
them.
So
I
think
that's
that's
really
good
for
the
screening
yeah,
so
paul
stapleton.
A
My
colleague
has
he's
getting
the
asset
up
and
running
already
and
he
is
going
to
have
that
ready
by
next
wednesday.
So
he
is
ready
to
test
the
evaluation
of
these
compounds
versus
mercer
from
next
wednesday.
So
I
gave
him
an
approximation
of
like
10
compounds
or
so
that
we
were
going
to
send
them
like
on
wednesday.
Is
that
still
about
right?.
A
Great
I'll
check
how
much,
but
I'm
assuming
it's
just
milligram
levels.
A
That's
good
so
we'll
get
some
data
back,
just
really
quick
for
the
talks.
There
is
a
bit
of
a
delay
to
that
just
because
of
lockdown
at
the
moment.
A
It's
not,
as
I
think
someone
said
at
a
previous
meeting
on
one
we
met
in
person,
but
it's
not
crucial
that
we
do
that
immediately
because,
of
course
we
want
to
know
you
know
something
about
potency
first,
but
I
will
keep
monitoring
that,
but
I
think
if,
given
the
the
paul's
having
to
do
the
mercer
screening,
I
think
that
we
don't
need
to
worry
too
much
about
alternatives.
A
E
A
Okay,
but
I
think
that's
that's
okay,
anyway,
you
know,
I
think,
we're
good
to
go
with
that,
just
because
I've
got
the
screen.
Maybe
I
should
just
carry
on
with
with
the
remainder
of
this
for
the
moment,
so
I
was
just
going
to
mention
that
we
still
do
have
this
interest
in
in
fisa
from
pfizer
to
measure
some
transformations
of
these
molecules.
We,
you
know
we
were
going
to
send
actives
and
inactives
right
are
we
are
we
in
a
position
to
do
that?
A
D
Yeah
so
I've
re-synthesized
osa
822,
which
is
the
thiophene
and
osa
820,
which
is
the
dimethoxy
and
that's
the
inactive
compound.
Okay.
D
A
So
I
think
that
we
should
take
them
up
on
this
offer
and
I
I
will
go
and
check
that
that's
still
good
and
check
how
much
they
need
yeah,
because
they're
happy
to
do
it
in
parallel.
Then,
oh,
so
sorry,
just
on
this,
we
were
talking
there
last
time
about
the
an
inactive
control
so
which
is
relevant
to
this
thing.
So
we
do
have
one
now
right.
A
That's
good
just
on
the
on
the
hyphen.
D
Yes,
I
think
the
part
of
the
idea
behind
re-synthesizing
the
thiophine
was
to
use
that
as
sort
of
an
internal
control
in
the
activity.
Assays.
B
A
For
sure
I
had
a
really
good
conversation
with
the
company
haifa
who
are
interested
in
working
with
us.
They
are
discussing
internally
about
the
what
they
can
do
and
then
we'll
learn
about
that
next
week.
I
think
so
they're
having
a
meeting,
but
it
was
an
interesting,
scientifically
interesting
meeting
about
what
they're
able
to
do
with
with
similar
stuff
to
the
pfizer
group,
and
we
were
talking
about
a
little
bit
different,
but
we
were
talking
about
what
they
might
be
able
to
do
with
us
looking
promising.
A
But
I
can't
confirm
anything
here,
but
I
will
report
back
on
what's
possible.
So
that's
promising.
Anyway,
it
was
a
fun
conversation
and
they.
A
Okay,
I
don't
think
there's
anything
on
the
oh
yeah,
so
the
just
reporting
back
on
the
gsk
conversation.
So
I
was
in
touch
with
the
team
who
reported
the
these
molecules
initially
from
gsk,
and
I
was
in
touch
with
the
corresponding
author
of
that
article,
james
callaghan,
who's
in
gsk
still,
and
we
had
a
long
conversation
about
things
and
I've
sent
him
a
summary
of
what
we
talked
about,
and
I
wanted
him
to
check
what
I
could
say
publicly.
So
I've
done
that
and
I'm
just
waiting
a
reply.
A
I
mean
yeah,
I
I
should
check
it
first
before
I
say
anything
because
I
don't
know
what's
proprietary
and
what
isn't?
As
you
know,
the
paper
where
these
compounds
were
reported
was
originally
for
a
kinase
project,
so
you
can
imagine
that
a
lot
of
the
med
chem
that
was
done
was
trying
to
optimize
for
kinase
inhibition
and
not
necessarily
antibacterial
activity.
A
A
5,
I
think
it's
in
it's
in
one
of
the
the
links
on
the
wiki
about
the.
A
And
you
know
they
published
something,
and
I
can't
remember
if
they
called
the
shops
when
articles,
but
they
certainly
published
it.
So
a
lot
of
stuff
was
done,
but
it
wouldn't.
It
wasn't
necessarily
based
on
the
thing.
A
Okay
and
the
other
things
are
again
just
design
criteria.
So
this
sorry,
just
on
this
thing
about
design
criteria,
have
we
because
it
keeps
on
coming
from
the
minute.
So
maybe
we
should
try
and
convert
it
to
the
wiki.
Is
this
in
the
wiki
now
this
idea
of
keeping
a
log
p
and
predicted
clearance.
D
A
A
Yeah
thanks
for
putting
the
same
thing
up,
it
occurred
to
me
as
I
was
writing
to
the
to
the
guy
johannes
who
we
were
in
touch
with,
and
thanks
for
putting
us
in
touch
with
them.
Chris.
A
It
occurred
to
me
that
it's
quite
neat
what's
going
on
here,
because
we'll
be
getting
data
from
monash
and
and
hopefully
from,
for
example,
pfizer
or
heifer.
You
know
these
guys
and
we
will
then
be
able
to
compare
what
we
see
with
the
predictions
which
is
going
to
be
quite
neat
actually,
and
I
think
I
think
the
people
who
make
the
software
will
be
quite
interested
in
what
we
find.
C
Yeah,
I
mean
I've
worked
with
johannes
a
few
times
and
he's
very
keen
on
building
the
applicability
domain
of
the
the
software.
So
if
we
have
new
results,
I'm
sure
he'll
be
really
interested.
A
This
thing
about
community
updates
again
it
just
still
stands.
It
keeps
coming
up.
I
guess
we're
just
all
pushed
for
time
when,
when
we
get
these
first
mrsa
results
from
four
stables
and
I
recommend
another
video,
but
let's
keep
that
on
the
agenda
for
that,
because
I
think
it's
important
to
highlight
you
know
new
things
and
the
the
last
thing
I
was
going
to
talk
about
was
this
stuff
to
do
with
the
active
against
other
bacteria
right.
The
original
coad
data
so.
D
D
No,
I
emailed
bill
and
alvaro
to
see
if
they
have
it,
and
I
just
heard
back
from
alvaro
today
he
said
he
doesn't
have
it,
but
bill
probably
would
so
I
think
maybe
matt
you
might
be
able
to
get
a
hold
of
him
better
than
I
could.
I
don't
know
I
just
haven't
heard
back
from
him.
Yet.
A
A
Okay,
that's
fine!
I
can
do
that,
no
problem,
all
right,
so
I
mean
just
in
terms
of
the
you
know:
clearance.
All
the
compounds
have
been
shipped,
so
five
of
the
nine
were
allowed
in
this
project
have
been
shipped,
so
we've
got
four
slots
left
and
the
moa
you
know
the
guy
is
going
to
be
doing.
The
experimentally
is
on
board.
So
I
think
we've
done
as
much
as
we
can
for
those
which
just
leaves
the
chemistry
right.
So
I
will
stop
sharing
when
you
guys
want
to
share.
D
Cool
yeah,
so
not
a
ton
new
from
me.
I
made
this
this
guy,
the
inactive
control,
the
dimethoxy
compound
and
then
just
working
more
on
these
sort
of
truncated
core
compounds,
so
I've
kind
of
worked
out
some
of
the
kinks
in
the
synthesis
I
just
need
to
scale
up
so
that
I
have
enough
material
to
push
forward
on
the
root,
and
then
these
ones
at
the
bottom
is
just
something
I
was
kind
of
thinking
about
in
terms
of
trying
to
modify
this
core
a
little
bit
more.
D
So
I
was
thinking
if
we
made
this
alkyne,
we
could
do
some
sort
of
triazole
library
but
yeah,
that's
not
necessarily
a
hypothesis
driven
but
just
sort
of
a
similar
heterocycle
that
maybe
we
could
think
about
looking
at
so
I
was
just
curious
to
get
thoughts
on
that.
D
I
was
thinking
something
a
little
bit
smaller
groups,
but
those
asides
are
hard
to
get
a
hold
of
so
yeah
yeah.
I
don't
know
it
might
not
be
that
great
of
an
idea,
but
it's
just
sort
of
a
brainstorming
thing
that
I've
came
up
with
yeah.
A
Have
the
has
the
alkyne
been
made
before
I
don't
know,
okay,
just
wonder
if
it's
compatible,
you
know.
D
A
E
And
then
so
for
my
stuff,
I
guess
similarly
not
too
much
new,
so
these
oxidized
sulfur
compounds,
so
I'd
made
the
cell
phone
boron
ester.
That
was
fine,
but
after
the
suzuki,
nothing
really
looked
like
the
product
for
the
sulfoxide
rnaster.
E
That
one
was
less
sure
about
the
actual
thing,
but
I
put
it
through
and
I
could
just
see
like
the
methylene
peaks
from
these
ones,
so
it
didn't
look
like
it
had
gone.
So
I've
tried
to
do
the
direct
oxidation
on
the
scale
of
dana's
compound.
E
So
it
looks
like
it's
worked.
The
yields
are
pretty
poor,
though
so
39
after
a
regular
home
and
then
14
after
reverse
phase,
which
is
like
3.9
migs.
E
So
I
mean
if
it
is
what
it
is,
then
I
guess
I
can
use
more
of
this.
If
we
have
enough
and
then
just
scale
it
up,
so
we
have
it
and
then
yeah.
I
was
thinking
of
doing
the
sulfur
oxide
oxidation
on
this
as
well
afterwards
to
see
if
that
works.
But
at
the
moment
it
doesn't
seem
like
it's
been
giving
like
an
n
oxide,
but
our
lcms
is
down
at
the
moment.
E
So
I
haven't
checked
and
then
the
other
thing
is
making
that
fennel
derivative,
so
that
worked
fine,
so
I've
got,
I
think,
10
megs
of
this.
So
we
can
send
that
for
the
next
one
as
well.
C
A
Yeah,
that's
true
yeah
you
mean
you
might
expect
the
yield
to
be
better
yeah,
it's
worth
a
shot,
if
you,
if
you
have
enough
of
it,.
A
What's
do
you
happen
to
have
a
a
sense
of
next
target?
I
mean
the
you
just
mentioned
some
there
dana.
I
guess
I
just
wondered
if
there
were
unfulfilled
targets
that
we
had
talked
about
right
at
the
start,
that
we
haven't
yet
got
to.
D
A
So
just
remind
me
on
the
on
the
imidazole
portion
without
sorry,
just
without
the
ring
there,
what
what
do
we
have?
That
is
like
methyl
and
stuff
sorry,
I
should
know
that,
but
I
forgot.
D
A
All
right
sounds
really
good
great
good
stuff.
I
mean,
I
think
that
is
that's
the
law.
Isn't
it
I
mean,
I
guess
you
know
we
want
to
try
and
just
get
as
many
of
those
you
know
purified
and
characterize
the
point
that
we're
happy
with
them
for
evaluation
on
wednesday
and
then
see
how
we
go
sound.
All
right,
yeah,
great,
we
are
done
in
24
minutes.
Was
there
any
other
business
that
we
should
be
taking
care
of,
and
these
research
meetings
should
be
quite
focused?
I
guess
nothing
else
right
well
good!
A
Well,
we
are,
we
are
good
to
go
well.
Thank
you
very
much
for
that.
I
will,
as
usual,
post
this
and
and
spruce
up
the
minutes
and
make
sure
the
action
items
are
live
because
I
think
we
deal
with
everything
which
is
good
all
right.
Thank
you
see
you
next.