►
From YouTube: Open Source Antibiotics Science Update Nov 27 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/43
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (UCL), Dr Chris Swain (Cambridge MedChem Consulting), Anthony Sama.
A
Hello,
everybody
welcome
to
open
source
antibiotics
on
friday
november.
The
27th
I'll
just
share
the
correct
thing
and
we
can
get
started.
Hopefully
that
is
now
the
right
thing.
A
Everyone
can
see
the
right
window,
hopefully
yeah,
all
right
good.
So
we
we'll
do
the
chemistry
update
in
a
minute
because
that'll
that
will
cover
the
most
recent
targets.
I
think
which
we're
looking
at
because
we're
still,
I
guess
we
were
talking
about
this
the
other
day,
we're
still
at
the
point
where
we
don't
yet
have
the
the
mechanism
of
action
stuff,
so
we're
still
waiting
and
we
don't
yet
have
the
cytotoxicity
data.
A
If
I'm
I'm
still
right
in
saying
that,
I
think
so
we
I
don't
have
either
of
those
two
things
so
we're
still
at
the
moment.
You
know
making
compounds
that
plug
sar
holes
essentially
and-
and
that's
fine
so
just
to
get
those
made
and
then
evaluated,
I'm
finding
out
I'm
trying
to
find
out
if
we
have
the
possibility
of
doing
another
round
of
potency
evaluation
before
christmas.
A
So
it's
on
me
to
ask
colleague,
paul
stapleton
about
whether
we
can
do
that
which
would
be
good
because
we've
been
making
some
more
compounds
right
and-
and
we
also
have
some
coming
in-
hopefully
from
laurie
so
important-
to
get
some
more
data
done
on
that
which
is
good.
But
I
think
you
know:
we've
got
lots
of
nice
ideas
about
compound
design
and
we
can
pursue
those
once
we
have
some
more
data
points.
A
B
A
I
mean
that's
what
we
can
do
at
the
moment,
because
we're
not
guided
by
something
else.
Do
you,
I
don't
dana.
I
don't
know
if
you
have
been
in
touch
with
laurie
recently.
There
were
just
two
things
that
came
up.
One
was
the
shipment
of
compounds
and
one
was
digging
up
things
like
tox
data
on
their
compounds.
C
Yes,
so
good
question
I
have
been
in
touch
with
her,
but
not
about
this.
I
can't
ask
her
about
that.
I
think
and
I'll
check.
I
think
when
she
shipped
the
compounds
last
time.
She
also
sent
me
a
spreadsheet
with
their
data,
so
I'll
just
double
check
that
that's
been
uploaded.
A
A
All
right
great,
so
we
just
need
to
yeah
finger
about
those
two
things.
That's
fine
and
okay,
that's
fine!
I
think
everything
else
is,
as
it
was
last
week.
Do
you
want
to
do
some
chemistry
just
to
bring
us
up
to
speed
with
what
we're
looking
at
yeah,
it's
been
purifications
this
week
right.
D
Mostly
you're
gonna
go
first
daniel
yeah,
that's
good.
C
Sure
so
the
nitrogen
linked,
so
I'm
looking
at
the
top
row,
I've
tried
two
different
sets
of
conditions
for
that.
I'm
just
getting
started
material.
I
am
going
to
put
a
buck
weld
on
in
the
microwave
I've.
I've
searched
the
literature,
so
I've
found
a
prep.
That's
been
done
on
sort
of
similar
substrates,
so
hopefully
that
will
work.
C
Then
the
core
compounds
with
the
tosal
substituent,
the
methoxy
core.
I
think
I
need
to
repeat
that
reaction,
because
after
purification,
it's
I've
still
not
got
it
clean
and
there's
just
not
enough
material
to
repurify
the
chloro
one
looks
nice.
So
that's
done,
then,
the
two
bottom
ones
the
benzophurrin
on
the
dndi
core,
is
clean
so
that
one's
good,
the
indole
is
there's
still
a
little
bit
of
something
in
the
nmr.
So
I'm
going
to
try
and
refrigerate
it
using
alvaro's
mixture
and
see
if
that
helps.
C
Yes,
yeah,
there's
only
a
little
bit
of
just
some
peaks
in
the
baseline
of
the
aromatic
region,
but
otherwise
the
nmr
looks
good.
A
C
A
It's
funny
about
the
the
top
row,
why
that's
being
tricky
and
I
mean
you're
sure
it's
obviously
sort
of
starter
material.
It's
not
like
the
bromines
come
off
or
something.
C
No,
I
checked
it
by
lcms
and
I
see
the
bromine
splitting,
so
that's
there.
Definitely
that
yeah
it
just
doesn't
really
look
like
it.
It's
doing
anything
besides
sitting
in
solution
and
stirring.
So.
C
A
A
C
Yes,
yes,
so
you
don't
start
with
that
brominated
core.
You
start
from
the
pyridine,
I
think
that's
an
aldehyde,
then
the
amino
pyridine
and
then
the
your
isocyanide.
A
B
What,
if
we
did,
what,
if
I
mean
probably
a
thial
linker
in
that
position,
wouldn't
be
too
terrible
to
make?
I
could
imagine
parathyrocrustal
sodium
hydride
just
repeat
the
top
one.
B
That
will
be
a
lot
hotter
than
the
nitrogen
will
be
in
terms
of
nucleophilicity.
A
D
Right
and
then
so
for
my
stuff,
so
these
five
compounds
are
done
about
20
megs
of
each.
So
this
last
one
with
the
two
methyl
I
got
about
like
twenty
percent
of
the
debruminated
core
and
only
six
percent
of
this,
which
is
like
three
migs.
So
I'm
gonna
repeat
it.
D
Yeah
yeah,
so
I'm
gonna
repeat
that
on
a
larger
scale
but
yeah
from
the
nmr.
I
can
see
that
this
methyl
group
is
splitting
the
protons
on
that
methylene.
D
Yeah,
but
it's
not
entirely
the
cleanest
right,
so
yeah,
I've
yeah
put
it
on
again
anyway,
and
then
these
other
two
reactions
are
just
from
doing
some
literature
searching.
So
I
was
looking
at
this
compound
with
the
nitrogen
removed
from
this
position
and
there's
an
old
paper
from
like
1979
that
does
this.
D
It's
also
in
german,
so
but
yeah
they
had
that
to
make.
You
know,
substituted
compounds
with
that
core,
like
the
procedure,
seems
easy
enough,
but
I
don't
know
and
then
can.
B
We
get
that
with
the
thing
installed,
the
tooth
of
the
pyridine.
D
Yeah,
so
I've
looked
at
this
substrate
with
the
pyridine
in
this
green
ring,
and
it's
not
cheap
and
going
from
the
like.
The
compound
without
the
bromine
is
also
not
too
easy
or
like
expensive,
but
yeah.
We
just
have
to
be
going
back
in
synthetic
steps
to
make
the
relevant
pyridine
compound.
For
that.
D
A
Ed
for
the
middle
line,
the
search
you've
done-
I
mean,
I
guess
we
want.
We
want
the
blue
and
the
green
rings,
and
we
want
something
on
the
nitrogen
yeah.
I
would
guess,
but
it
is
that
so,
if
you
just
search
on
that
core,
where
the
nitrogen
has
a
carbon
attached
to
it,
is
that
what
you
get.
A
Okay,
because
I
mean
we
could
tolerate-
you-
know
some
variation
there,
but
but
the
rest
of
the
the
payroll
with
the
two
aromatics,
I
think
is-
is
necessary,
yeah,
yeah
and
and
not
necessarily
specifying
it's
a
fennel.
Obviously,
because
yeah
it
could
be
a
pyridine.
D
A
So
just
be
careful,
you
search
terms,
I
suppose,
yeah,
because
I
mean
that
yeah,
it's
a
nice
reaction,
so
just
fiddly
to
have
to
roughly
find
to
have
to
make
starting
materials.
It's
just
a
bit.
A
D
Yeah
I
mean
I've
translated
it,
so
it's
just
in
solvent
yeah
I
mean
it's,
it
seems
pretty
straight
forward.
A
A
Okay,
that's
good
great!
That's
nice!.
A
And
then
so
yeah
the
stuff
by
heifer.
So
this
is
really
good.
We
have
now
done
the
paperwork
and
we
are
good
to
go
so
we
have
now
shipped
the
molecule
to
heifer
and
I
understand
it's.
It's
arrived
yeah
right,
yeah,
so
we're
good
to
go,
and
I
for
a
happy
for
me
to
say
that
we're
doing
this
work,
which
is
awesome.
So
this
is
a
you
know,
a
very
nice
in
kind
contribution
from
them
to
the
project
to
help
us
to
understand.
A
What's
going
on
with
these
molecules,
so
they
are
running
this
through.
They
have
a
collection
of
sip
enzymes.
So
it's
the
these
sort
of
polysips
kit
that
they've
got
which
they
sell
and
they're
gonna,
run
it
in
situ
for
us
and-
and
I
think,
a
human,
liver,
s9
enzyme
in
oxidation
mode.
A
So
this
is
kind
of
one
of
the
things
that
they
offer
as
a
service
and
they're
doing
it
for
for
us,
because
it's
an
open
project-
and
they
are
also,
I
think,
going
to
try
and
run
if
they
can
some
glucoronidation
stuff
to
see.
If,
if
that
is
also
a
way
in
which
the
the
molecule
is
metabolized
and
they
again,
if
they
have
capacity,
they
have
a
microbial
panel,
which
they
might
run
this
thing
against,
so
there's
a
bunch
of
stuff.
A
They
can
do
the
the
deal
here
and
again
it
does
depend
on
how
it
goes
and
how
difficult
things
are,
and
they've
been
up
front
about
that.
You
know:
there's
not
infinite
resources
here.
A
The
deal
is
that
if
they
get
something
simple
as
a
transformation
of
the
molecule
into
sort
of
one
other
thing
that
they
will,
you
know
try
and
figure
out
what
that
thing
is
obviously,
and
they
are,
they
are
happy
to
try
and
do
some
scale
up
work
to
do
some
preparation
of
that
molecule
so
that
we
can
more
accurately
characterize
it
so
likely
that
the
screen
stuff
will
happen
in
about
a
week
and
a
bits
time
and
then
maybe
after
christmas
will
be
any
kind
of
scale
up.
A
If
there
is
scale
up
to
be
done,
ed
may
have
to
make
more
of
that
molecule
and-
and
we've
already
spoken
about
that,
because
they
need
quite
a
bit
of
molecule.
For
that
again,
it
depends.
You
know
what
kind
of
reaction
we
see,
but
this
is
really
awesome,
so
it
could
be
a
way
of
us
getting
some
more
information
about
what
exactly
happens
to
this
molecule.
So
we
could
do
some
metabolic
id,
which
is
great
so
we're
leaving
it
and
we'll
get
updates
and
I'm
allowed
to
share
those
updates.
A
So
they've
been
really
good
about
being
able
to
share
things
which
is
very
nice,
so
I'm
glad
that's
happening.
It
was
just
a
a
paperwork
delay.
It
was
nothing
difficult
about
it.
It
was
a
paperwork
delay
and
then
all
the
other
stuff.
So
we
you
know
we
remember
from
last
week
the
other
things
that
we
were
talking
about.
A
And
other
things
I
haven't
had
a
chance
to
do
anything
on
me.
It's
been
a
busy
teaching
week
for
me,
but
I
haven't
had
a
chance
to
do
anything
on
this,
but
I
will-
and
there
was
the
other
thing
we
were
just
talking
about
for
lab
archives-
molecule
sketchbook
facility.
Have
you
guys
been
able
to
assess
this.
D
Yeah,
so
I
don't
know,
I'm
not
too
convinced
about
it.
Really,
you
draw
a
molecule
yeah,
so
let
me
go
on
the
page.
So
shall
I.
D
D
Right
so,
oh
I
should
say
so
what
I've
normally
been
doing
is
putting
strings
at
the
end
of
the
page.
So
for
this
one
I
got
rid
of
that
and
replace
it
with
the
chemical
sketching
thing.
So
this.
D
D
E
D
E
Because
there
you've
got
the
small
string,
you
have
all
the
aromatic
rings
as
old
atoms
as
lowercase
c,
which
are
lower,
which
is
an
aromatic
atom.
When
you
draw
it
in
kendra
and
you
do
the
calculate
form,
you
have
effectively
a
ring
containing
alternate
all
aliphatic
carbons,
with
double
bonds
between
them.
A
Because
it
doesn't
do
that
yeah,
that's
a
feature
request
yeah,
and
what
about
you
so
using
their
smiles
to
them?
Yeah
googling!
That.
A
Up
because
I
it
should
right,
I
mean
if
it's,
if
it's.
A
If
it
is,
if
it's
adding
it
to
the
page,
when
you
draw
it.
D
A
In
the
spreadsheet
of
all
molecules,
we
have
smiles,
and
I
guess
we
just
have
one
of
these,
not
both
right.
We.
E
E
A
I
mean
we
need
this
fixed
really
and
I'm
not
sure
what
the
best
solution
is.
We,
the
thing
we're
trying
to
fix
is
making
sure
that
we
can
search
from
the
outside
of
the
lab
notebook
and
find
molecules
that
we're
working
on
without
having
to
paste
in
the
strings.
That's
the
solution
that
we
want
and
if
the
strings
appear
on
the
page,
then
we're
set
and
we've
shown
that,
but
at
the
moment
there's
a
break
between
drawing
something
with
the
widget
and
the
relevant
metadata
appearing.
A
A
A
Yeah,
it
would
make
a
big
difference
if
we
could
do
that
and
then
chris
I
remember
you
was
you
were
you'd
submit
it.
I
think
our
page.
E
Yeah
they
did
say
it
would
take
a
week
to
index
so
it
hopefully
it
would
be
there
next
week.
A
Okay,
fine,
okay,
great
thank
you
and
I
think
that,
on
in
terms
of
the
in
terms
of
the
other
action
items,
I
think
we're
all
set
so
yeah
we
in
that
case
we
wait
for
mechanism,
action
data
and
talks
data.
Those
are
the
two
big
things
and-
and
we
keep
talking
about
those
synthesis,
I
think
yeah
all
right
was
there
anything
else.
Anyone
wanted
to
talk
about
hi
ben.
We
we
just
we're
kind
of
basically
finishing
up.
I
think.
A
We
also,
I
was
on
me.
G
A
Hi,
we
were
just
saying
we're
waiting
for
the
talks
data
when
we're
waiting
for
mechanism
action
data
and
some
comments
are
coming
in
from
laurie
at
some
point
and
those.
G
A
A
Yeah,
sorry,
do
you
want
me
to
do
you
want
me
to
share
that
in
case
you.
G
Don't
know
it's
okay,
I
mean
I'll,
maybe
maybe
I'll
do
maybe.
If
I
have
time
when
I
join
next
week,
just
so
you
know
so
some
of
those
comp
I've
just
had
a.
I
just
said
the
the
article
we
wrote
on
that
serious
release
from
isis
was
accepted
today,
so
it
should
be
published
pretty
soon
once
you've
gone
to
the
open
access
page,
so
there'll
be
a
little
bit
of
data
in
there
on
that
and
all
of
the
like.
That's
on
experimental
and
whatnot,
so
great.
If
you're
interested,
that's
brilliant.
G
Guys,
if
there's
some
way
that
you
can
get
the
like
the
saturated,
like
the
five
five,
where
it's
heavy
saturated,
if
we
can
get
a
couple
of
those
to
test
that
would
be
cool,
I'm
trying
to
think
of
the
best
thing
doing
it
probably
send
it
to
laurie.
I
don't
know
it
depends
whether
it's
where
they
are,
whereas
molecules.
A
Yeah,
that's
a
good
idea.
Yeah
yeah,
absolutely
always
happy
to
do
that
kind
of
thing
might
be
better.
A
On
our
lead
compound
from
biosciences,
you
may
know
them
that
do
a
bunch
of
metabolic
stuff
in
the
uk.
E
F
A
Okay,
see
you
next
time
around
yeah.