►
From YouTube: Open Source Antibiotics Science Update Jul 31 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/22
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (all University College London), Dr Chris Swain (Cambridge MedChem Consulting).
A
Okay,
all
right
so
welcome
to
open
doors,
antibiotics
series,
two
update
meeting
on
friday,
the
31st
of
july.
The
meeting
will
involve
us
going
through
the
to-do
list
from
last
time
and
just
updating
everybody
and
generating
a
new
issue
and
just
going
over
some
of
the
latest
chemistry
for
the
series.
A
B
A
All
right
great,
so
we
so
today
we
don't
have
alvaro.
I
think
he
just
said
he
couldn't
make
it.
A
Unfortunately,
so
chris
alvarez
was
the
cameras
who
did
a
bunch
of
this
work
at
unc,
and
he
joined
us
last
time
to
talk
about
the
chemistry
he's
now
at
the
university
of
edinburgh.
But
okay
he's
following
the
project,
which
is
great
and
knows
about
where
samples
are
and
things
like
that
subscribe.
A
You
are
dlc
all
right
and
we'll
see
if
mandatory
show
them
I'll
go
down.
Okay,
so
lab
books
and
stuff
in
our
link.
So
I'm
gonna
just
get
rid
of
that
completely,
because
that's
all
done
and
this
thing
about
the
samples
at
unc
already
again
again-
that's
just
complete
and
we
need
to
make
sure
that
the
samples
at
unc
are
afforded
to
monash,
which
is
on
me
still.
A
Here
we
had
a
little
email
correspondence
with
lee
grazie
unc,
who
is
going
to
be
doing
the
mechanism
of
action
experiments
and
he
was
asking
about
the
base
cell
type
and
I
wrote
to
say
I
didn't
quite
understand
what
he
meant
and
I
just
say
that
basically,
the
cell,
that
we're
interested
in
is
mrsa,
and
so
I
think
he's
taken
that
as
being
that's
fine,
so
I
think
we're
good
to
go,
though
I
just
need
to
have
chase
that
he's
happy
to
do
the
experiments,
but
that
is
ultimately
the
you
know.
A
C
I'll
just
this,
I
guess
we
should
see
if
they
need
more
of
that
compound
to
be
made
for
those
experiments
or
if
they
are
fine,
with
the
amount
that
they
have
at
umc
sure
yeah.
A
Fine
yeah
good
gonna
ask
how
about
that.
I
think
she
knows
about
the
stocks.
They've
got
and
the
most
measurement
of
the
in
vitro
parameters.
Yeah,
there's
no
change
here,
so
they
have
afforded
everything
they
need,
and
we
just
have
to
make
sure
that
this
is
on
me
again.
I've
just
got
to
forward
that
to
the
unc
team
and
say
this
is
what
the
requirements
are.
Please
ship.
A
They
were
very
particular
about
that.
I
think
it's
quite
difficult
to
get
compounds
in
to
monash
unless
they're
labeled
properly,
that
was
that
was
all
it
was
on
the
talks
and
mrsa
screening.
So
yeah
I
had
a
word
with
mark
blaskovich
about
coat
and
they
are
happy
to
take
the
compounds
in,
but
I
think
that
their
primary
grant
has
run
out,
which
just
means
that
the
screening
is
not
quite
as
rapid
as
it
used
to
be
back
in
the
day.
A
I
was
noticing
actually
that
these
compounds
originally
were
screened
at
covered.
I'd
forgotten
that
point.
It
would
be
nice
to
continue
that
we
do
have
the
opportunity
of
getting
the
screening
done
here
by
two
of
my
colleagues
who
are
happy
to
do
it
because
of
the
lockdown
and
and
because
it's
now
august
things
are
a
little
slower
than
maybe
we
were
hoping
for.
I
think
so.
A
I
guess
these
two
things
are
still
possibilities:
shipping
to
coad,
although
the
grants
finished
or
doing
things
locally,
which
is
obviously
quite
attractive,
I
don't
know
of
any
other
places
that
would
do
these
two
essays
together
on
a
regular
basis.
It's
like
a
service
mrsa
and
generic
toxicology.
I
just
don't
know
so
again
if
anyone's
got
any
suggestions
and
all
ears.
Otherwise
I
think
we
should
proceed
with
one
of
these
or
the
others.
A
D
A
A
Okay
and
and
like
I
said,
the
reason
why
I'm
I'm
just
keen
to
try
and
do
a
kind
of
reasonably
rapid
turnaround
so
that
we
can
synthesize
and
evaluate
on
a
reasonably
tight
cycle
rather
than
making
50
compounds
and
finally,
the
more
active
you
know
all
right.
So
that
brings
to
a
synthetic
chemistry
I'll
stop
share.
If
somebody
would
like
to
share
this.
D
C
So
I
was
trying
to
make
the
ornate
ester
of
this
brominated
core,
the
egt467.
I
ran
that
reaction
overnight.
It
got
some
conversions
to
product,
but
mostly
starting
material.
C
So
then
I
just
ran
the
borrelation
on
the
other
coupling
partner
and
that
on
my
test,
reaction
worked
fine
and
I
was
able
to
purify
it
and
then
run
the
suzuki.
So
I
just
need
to
purify
that,
but
I
think
the
reactions
work.
C
So
I
also
set
up
three
other
correlations
of
our
other
building
blocks
and
then
those
will
be
coupled
to
the
core
as
well
and
then
that's
our
final
product,
so
yep,
that's
what
I've
been
up
to
this
week
and
probably
a
bit
of
what
I'll
be
up
to
next
week.
A
Also,
okay,
the
terry
just
once
at
the
where
I'm
just
trying
to
okay
right.
So
you
tried
the
you're
just
training,
both
ways
around.
C
So
the
first
one,
the
120
building
block
going
to
the
124
product
is
a
resynthesis.
The
rest
of
them
are
novel
right.
A
C
A
C
D
A
Yeah
great
all
right,
that's
that's
fantastic.
Okay,
the
the
comment.
One
comment
came
up
on
the
call
that
we
just
had,
which
I'll
mention
in
a
minute
about
solubility.
I
guess
we
there's
no
problems
with
these
guys
being
solid
within
organic
solvents
right,
but
we
don't
yet
know
anything
about
the
solubility
aqueous.
C
C
B
A
Yeah
also
be
nice
yeah
to
keep
an
eye
on
their
general
ability
to
withstand
lab
temperatures
like
today.
You
know
without
going
off
so
just
keeping
an
eye
on
how
stable
they
are.
A
All
right,
great
just
sorry,
just
remind
me,
because
I
should
know
this.
What,
besides
this
variant,
what's
the
next
variant
that
we're
thinking
about
is
it?
Is
it
on
the
imidazole
member
brain
just
remind
me
what
the
kind
of
next
big
chunk
of
stuff
we
were
thinking
about,
doing.
C
Yeah,
so
not
too
much,
I
was
looking
at
making,
basically
the
unsubstituted
imidazole
or
just
the
dye,
the
diurel
substituted
right
right
and
then
so
I
found
literature
procedure,
whereas
essentially
you
can
just
do
a
suzuki
between
the
pyridine
and
the
core
and
then
bromine
and
do
another
suzuki.
So
it
seems
pretty
you
know
not
too
complicated
to
make
and
then
yeah
we'll
have
to
do
a
little
bit
more
planning.
I
think
on
what
to
make
next
beyond
that,
so
I
was
thinking
I
could
make
the
nh
and
maybe
the
n-methyl.
A
Yeah,
if
memory
serves
the
prediction
of
clearance
here
was,
was
on
the
thing
as
it
was,
which
of
course,
you've
gotten
rid
of
in
the
bottom
compound.
B
A
The
other
combats
you're
making
and
also
on
the
on
the
unsaturated
five-membered
ring
that's
fused
to
the
emitters,
all
right.
C
A
A
So
that's
really
good!
Thank
you
if
you
just
after
the
means,
drag
that
file
to
here
somewhere.
So
we
have
it
kicking
around
compound
numbering
thing,
I'll
I'll,
get
rid
of
this
eventually,
because
we
dealt
with
that
last
time
and
then
so
yeah
on
on
number
eight,
we
have
had
interest
from
pfizer
in
doing
the
metabolic
work,
which
is
great,
and
so
the
default
plan
is
to
send
some
compounds
when
we
have
them
for
that
kind
of
bio.
A
Functionalization,
work,
try
and
isolate
the
metabolites
and
see
if
they're,
active
and
and
scott
has
very
kindly
put
me
in
touch
with
uk
company
haifa.
Who
have,
I
believe,
because
I
scanned
my
inbox
listening
this
morning-
sent
me
a
follow-up.
So
leave
that
with
me
and
I'll
see
what
I
can
report
back
about,
whether
you
could
do
any
work
together.
Just
gotta
read
some
emails
and
check
for
something
confidential.
A
Which
is
good
because
that
would
be
interesting
to
see
I
mean
it
was
actually
interesting.
Looking
at
the
sar
just
now
on.
My
previous
call
and
thinking
about
some
of
the
more
active
compounds
are
the
ones
with
the
more
obvious
metabolic
liabilities,
and
so
it
doesn't
actually
make
you
think
that
perhaps
it's
something
to
do
with
a
metabolism.
A
It's
certainly
something
that's
worth
investigating
further.
We
just
to
bring
up
the
speed
here.
Chris
on
point
nine.
Here
we
were
wondering
about
whether
there
was
anything
as
a
kind
of
very
rough
and
ready
in
vitro
sort
of
chemistry
lab
assay,
for
if
a
compound
was
liable
to
be
subject
to
in
vitro
metabolic
clearance
or
oxidation.
A
I
know
there
was
a
paper
a
while
back
for
that,
a
mimic
of
allied
oxidase
type
activity
and
we
were
just
trying
to
find
out
whether
there's
a
sort
of
a
little
bit
of
a
kind
of
standard
way
of
seeing
where
the
compounds
tend
were
likely
to
be
cleared
well
by
doing
a
sort
of
chemistry
lab
test
sort
of
tlc
based
conversion
assay.
But
we
couldn't
really
find
anything
was
a
standard
here.
But
if
you
ever
seen
anything
like
that
or
if
you
have
any.
B
No,
I
I
have
not
I'm
afraid
I
mean,
I
think
the
in
silico
experiments
are
probably
as
reliable.
A
Yeah,
okay,
fine,
we
can,
we
can
get
rid
of
this.
It's
really,
I
think,
if
we're
happy
with
the
within
silicon
predictions-
and
we
start
making
confidence,
we
can
we
can
just
send
it
to
march,
we
can
go
from
there.
That's
fine!
All
right
number
10
was
the
call
that
we
just
had.
A
So
I
can't
I
can't
really
say
anything
yet
because
I
haven't
got
it
clear,
but
we
just
had
a
very
good
conversation
with
james
callaghan
at
gsk,
who
was
the
the
corresponding
author
on
the
original
article,
which
reported
these
compounds.
A
So
we
just
chatted
to
him
about
the
origins
of
this
series
and
what
they
found
out
about
the
series
and
I'll
I'll
write
out
some
things
to
clear
with
him
about
what
we
can
reveal
publicly.
The
aim,
of
course,
of
their
work
was
not
mrsa.
The
aim
of
their
work
was
out
five,
so
the
kinase
inhibition
work.
A
So
you
know
it's
not
as
if
they're
necessarily
sitting
on
a
treasure
trove
of
information
about
antibacterial
activity,
but
obviously
we're
trying
to
ask
for
whether
they
have
any
compounds
that
are
structurally
related
to
what
we
have.
Firstly,
and
secondly,
they
might
be
the
share
and,
secondly,
whether
they
solve
any
of
the
issues
to
do
with
perhaps
fast
clearance
or
low
aqueous
solubility.
A
If
that's
a
problem,
you
know
those
things
and
so
he's
going
to
do
a
bit
of
rooting
around
and
putting
us
in
contact
with
some
other
people
there
to
make
sure
that
we
can
extract
what
they've
learned
from
this
series
as
it
went
on
like
I
said,
it's
mostly
relevant,
I
think,
to
the
early
stages
of
their
project
before
they
started
to
optimize
for
the
indication
that
they
wanted
for
the
target
that
they
wanted,
but
we'll
see
so
I'll
try
and
get
something
to
share
with
everybody
after
I've
got
it
played
by
james,
but
that's
promising
and
then
there's
just
other
recurring
things
about
design
criteria.
A
So
yes
keep
an
eye
on
on
p
and
clearance
and
try
and
promote
these
issues,
and
these
meetings
and
everything
else
by
the
usual
channels
to
bring
people
in
if
they're
interested.
B
The
the
smart
steps,
one
where
predicted
metabolism
but
there's
also
one
called
fame
by
johannes
kirschmeyer.
I
think
it
is
spelling,
sorry
well,
the
the
software
is
called
f
f,
a
m
e
fame,
fast
atomic
metabolizer,
or
something
like
this.
B
A
Great
all
right,
all
good
was
there
anything
else.
We
have
forgotten.
A
I
think
we're
all
good
we're
in
good
shape.
Right,
I
mean
that's
everything.
I
found
a
very
useful
thing
in
github
that
little
list
of
action
item
things.
That
is
awesome.
A
B
A
Yeah
we
danny
did
a
bunch
of
work
on
this
and
yeah.
You
want
to
talk
about
it.
C
Sure
it
was
proven
a
while
ago,
so
I'm
not
sure
if
I
remember,
I
think,
where
we
ended
up
was
there
doesn't
seem
to
be
immersive
specific
tpp
that
you
know
we
could
maybe
lift
from
guard
p
or
things
like
that.
So
kind
of
forget,
I
think
essentially,
sort
of
the
one
that
I've
basically
made
up
is
what
we
have
right
now,
which
is
we've
got
acceptable
and
ideal,
and
then
I
think,
we'll
just
sort
of
focus
on.
C
Kind
of
one
of
the
earlier
ones,
maybe
like
eight
or
nine,
no,
not
eight
ten
there.
It
is.
Oh,
no
sorry,
it's
11.!
It's
11.
B
And
I
did
actually
ask
about
single
target
pathogen
and
whether
people
would
find
that
attractive,
and
I
think
the
my
impression
was
that
the
the
scientists
thought
it
was
a
an
appropriate
approach,
because
you
don't
really
want
to
be
carpet
bombing.
The
entire
bacterial
gene
biome.
B
A
B
Well,
the
thing
is
that
normally
they
in
antibiotics,
they
like
to
do
a
clinical
trial
with
something
like
urinary
tract
infection,
because
your
patients,
whilst
uncomfortable
rarely
die,
whereas,
if
you're
going
the
sort
of
indication
you're
talking
about
there's
likely
to
be
a
very
high
death.
B
A
A
C
Yeah
we
yeah,
we,
I
think,
on
their
website.
They
have
which
I'm
pretty
sure
we.
A
That's
an
interesting
point,
though:
yeah
yeah
yeah,
maybe
when
I've
saved
this,
you
could
maybe
update
that
comment
or
something
about
that.
That's
a
really
good
point.
Sure.
C
A
Okay,
fantastic
anything
else
I
mean
so
I'm
yeah,
I'm
away
for
a
couple
weeks.
So
I
guess
we
we
can
pause
these
meetings
or
you
can
just
have
them
or
we
can
just
keep
on
updating
this
and
try
and
make
progress
here.
I'm
easy.
Whichever
way.
A
Okay,
great,
thank
you
very
much
for
coming
along
guys
and
thanks
for
coming
along
chris.
A
A
All
right
so
again
I'll,
try
and
now
that
I
know
what
I'm
doing
I'll,
try
and
post
the
the
recording
quickly
and
just
make
sure
it's
up
there
again
just
to
try
and
make
sure
that
I'm
always
tagging
it
with
open
source
analytics
to
make
sure
they're
easy
to
find.
It
means
that
other
people
can
post
things
to
youtube
if
they
want
to
and
have
it
all
linked,
yeah
all
right,
wonderful,
thanks
for
coming
along,
see
you
all
again
soon.
Okay,
thanks.