►
From YouTube: Open Source Antibiotics Science Update Aug 21 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/23
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (all University College London),
B
A
Okay,
all
right
all
right.
Welcome
back
to
oh
from
source
antibiotic
series,
2
research,
progress
meeting
on
friday
august
21st
2020.
A
This
is
just
a
quick
update
meeting
after
summer
holidays
and
a
bit
of
a
break
to
catch
up
on
a
few
of
the
things
which
hopefully
are
on
screen
there,
which
we
are
putting
on
to
issue
number
22
on
the
github
site
for
open
source
antibiotics
series,
2
diarrhoeas,
so
we're
just
going
to
catch
up
on
a
few
things
and
and
move
forward
some
video
items
and
catch
up
on
chemistry.
A
We
didn't
advertise
this
meeting,
so
it's
the
core
team
at
the
moment,
all
right,
but
after
the
meeting
I'll
post,
the
video
and
people
can
see
what
we
talked
about.
Okay,
so
the
just.
The
first
item
was
the
really
crucial
thing
which
we
need
to
get
done,
which
is
the
measuring
of
the
in
vitro
clearance
and
solubility
of
samples
in
this
series,
which
are
held
at
unc
and
which
needs
to
be
measured
in
monash,
and
the
two
sides
are
now
in
touch
with
each
other.
A
So
I
got
instructions
from
karen
white
at
monash
and
I
forwarded
those
to
carow
wells
at
unc
for
shipping
of
samples,
so
that,
hopefully,
is
all
done.
The
samples
need
to
be
shipped,
of
course,
but
we
decided
on
the
five
samples
and
they'll
be
sent,
hopefully
asap
depending
on
how
things
are
at
unc,
with
a
lockdown
but
that's
closed
and
I've
completed
an
action
all
right.
That
is,
you
know
the
number
one
priority
really
in
the
sense
that
this
whole
project
is
about
trying
to
fix
that
clearance.
A
So
hopefully
the
data
will
help
us
to
plan
better
compounds
in
the
next
round.
All
right
number
two
is
the
mechanism
of
action
and
stuff.
So
I
don't
think
there's
been
any
progress
on
this
in
the
sense
that
we
we've
updated,
lead
grades
at
unc
with
the
idea
of
mrsa
being
the
cell
type
we
want
to
use,
but
I've
had
no
other
contact
since
then,
so
that
action
is
on
me
to
so
now
I
complete
it
on
there
on
number
two
I'm
going
to
write.
A
This
is
also
on
me
still
to
chase
trying
to
do
the
experiment.
There's!
No.
I
don't
think
there's
any
need
for
a
delay
here,
because
we've
got
samples
and
we
know
experiments
need
to
be
done.
So
it's
just
a
question
of
hassling
all
right
number
three
is
the
same
thing
I
think.
So
it's
just
the
same
thing
as
number
one.
So
this
is
all
completed.
I
mean
in
a
sense
it's
out
of
our
hands,
but
we
need
to
monitor
whether
the
samples
are
going
to
monash.
A
Number
four
is
the
mrsa
and
top
screening
all
right,
so
I'm
just
about
to
get
back
in
touch
with
paul
and
andreas
to
ask
them
about
whether
they
have
people
in
the
lab.
Who
can
do
the
screening
versus
mrsa
and
generic
sort
of
toxicology
screen
against
mammalian
cell
lines?
I'm
pretty
sure
that'll
be
okay,
but
I
just
need
to
double
check
the
time
scale.
A
A
I
drafted
that
email
to
seven
click
send
in
terms
of
whether
there
was
a
backup
right.
So
our
two
options
here
are
internally
at
saab
or
at
coat,
and
I
guess
there
was
this
question
about
whether
there
were
any
other
options.
We
could
consider
who
might
do
this
as
a
service?
Did
anybody.
A
Or
has
some
thoughts
about
whether
there
was
another
service
we
could
use
like
the
newly
revamped
public,
health,
england
or
something
any
other
places?
I
might
do
it
in
london
or
around.
If
you
could
google
search
or
something
to
see,
if
there's
anything
that
we're
missing,
they
might
do
it
as
a
service.
That
would
be
very
useful.
A
Because
I
don't
want
to
miss
something
obvious
where
we
could
just
submit
samples
to
get
screened
all
right,
synthetic
chemistry,
so
we
can
do
an
update
here.
Just
on
the
I
saw
that
the
slide
that
we
had
last
time
we
put
on
the
issue
for
last
time,
which
was
great
if
you
could
also
just
try
and
upload
it
to
the
the
file
store.
A
If
you
know
what
I
mean,
so
the
tab
which
says
code
has
a
shared
file,
store
and
there's
something
there
for
synthetic
chemistry.
If
you
could
just
additionally
put
the
file
there,
that
would
be
very
helpful
because
that's
a
place
where
people
might
look
for
updates
and
yeah-
I
mean,
I
guess
the
powerpoint
powerpoint's.
The
main
thing
can
draw
if
you
want
to,
but
powerpoint
is
the
main
thing
so
the
last
week
one
and
this
week's
one
drag
here
and
then
upload
will
be
helpful
just
to
keep
it
in
two
places.
A
A
B
Okay,
cool
yeah,
so
I've
done
the
suzukis,
the
oxazole.
I
did
not
get
the
suzuki
products.
I
was
getting
mainly
debromination
of
the
starting
material,
the
other
ones,
I've
isolated
and
they
look
good
except
for
a
weird
peak.
In
the
end,
the
chloroform
nmr,
which
is
not
there
in
the
methanol
I
took
one
in
methanol
and
the
lcms
looks
good
too
so.
D
B
The
so
the
top
left
the
product,
the
first
three,
oh
yeah,
so
124,
125
and
126.,
I'm
seeing
the
same
thing.
So
it
looks
like
a
it
kind
of
looks
like
a
water
peak,
except
that
it's
at
like
2.5.
A
A
D
In
dmk127
127,
so
I
didn't
see
the
desired
product
at
all
and
the
major.
A
D
D
B
D
B
Right
so
I'm
getting
the
d
bromination,
so
there's
just
a
proton
there
and
then
this
two
other
peaks
which
I
they
have
mass
on
the
lcms.
But
I
can't
I
haven't
been
able
to
identify
what
those
are
okay,
so
yeah.
I
haven't
tried
to
isolate
them
because
I'm
not
sure
how
productive,
how
good
of
a
use
of
time
that
would
be,
but
I
do
have
the
crew
materials.
I
can
try
to
dig
a
little
deeper
on
that
one
if
you
think
it
would
be
worthwhile.
I
don't
know.
A
If
I
mean
if
one
two
four
one,
two
five
one
two
six
are
inactive,
then
maybe
there's
not
that
much
point.
D
A
B
Okay,
so
we'll
set
that
aside,
yeah
and
then
I've
been
also
been
looking
at,
making
the
sort
of
just
the
imidazole
core,
with
either
an
nhrd
and
methyl
so
for
the
nh.
I
tried
the
suzuki
on
just
the
unprotected
and
municipal
and
I
didn't
get
product.
So
now
I
put
a
title
group
on
it.
So
that's
the
literature
procedure
that
I
found
so
the
suzuki
I
think
has
worked.
B
So
I
need
to
purify
it
and
get
the
nmr
to
confirm
that
and
then
it's
just
further
steps
to
the
the
desired
product.
Then
I
also
tried
to
methylate
the
imidazole.
B
B
Yeah
yeah,
I
mean
I
think
I
can
do
maybe
an
hmbcs
figuring
out,
which
protons
are
coupled
to
the
methyl
right,
because
this
one
should
be
coupled
to
two
protons,
whereas
this
one
should
only
be
the
one.
A
So
they
may
have
if
someone
else
has
done
the
hard
work
they
may
have
defined
shift
for
the
protons
yeah
yeah,
okay,
all
right
great,
and
that
so
that
would
give
us
some
variation
there
right.
Okay,.
B
A
Absolutely
yeah
yeah
and
because
the
tritel
doesn't
have
that
problem,
I'm
guessing
it
goes
on
where
the
bromine
is
not.
B
A
Which
is
a
neat
neat
part
of
it,
yeah,
okay,
yeah,
and
what?
If
so,
if
you
get
so
the
right
hand
structure
if
you
get
there
with
r
equals
h,
so
in
other
words,
if
you
take
the
tritone
off,
then
it's
the
idea
to
then
put
something
on
the
nitrogen
again
or
is
it
just
have
it
as
the
nh.
B
We
could,
I
was
gonna,
just
send
it
as
the
nh
initially
and
then
with
the
smaller
methyl,
and
then
you
know
if
the
nh
is
inactive
with
the
methyl
is
active.
We
can
go
a
little
further
down
that
road
and
or
if
the
opposite
is
true.
Certainly
we
don't
necessarily
want
it.
Then.
A
Yeah,
I
mean
yeah
same
thing:
if,
if
you
put
an
r,
if
anything
on
that
final
compound
through
that
root,
then
again
you're
likely
to
get
isomers.
E
And
then
yeah
so
for
my
stuff,
so
I
finished
off,
making
those
first
top
two
compounds
just
making
the
boron
ester
and
then
doing
the
suzuki,
and
then
I've
been
working
on
making
these
oxidized
sulfur
metabolite
compounds
so
to
for
the
sulfoxide,
I
tried
to
do
it
with
hydrogen
peroxide
and
I
got
the
product
in
42.
But
then,
when
I
tried
to
do
the
borrelation
like
I
couldn't
really
identify
the
correct
product.
E
So
I
repeated
the
oxidation
with
some
different
conditions
and
I've
got
like
some
cleaner
sulfoxide
products.
So
I've
put
that
on
for
correlation.
It's
going
at
the
moment.
The
cell
phones
a
lot
easier.
That's
just
m
cpba
oxidation
93
of
that
correlation
is
also
really
good,
so
68
and
I've
put
that
on
for
suzuki
yesterday.
E
So
I
just
need
to
purify
that,
and
I
should
have
that
one
and
then
the
last
thing
was
that
we
were
thinking
of
making
the
derivative
without
the
pyridine,
so
just
with
the
fennel.
So
we
have,
I
guess,
a
control
compound,
because
I
don't
think
we
have
that
without
the
nitrogen
on
that
ring.
Okay.
So
this
first
step
is
going
at
the
moment
based
on
lit
it's
a
lot
nicer
than
with
the
two
pyridine.
E
A
Okay,
yeah
yeah,
I
can
imagine
it
is
going
to
be
nicer
and
less
soluble.
I
suspect
I
mean
aqueous
solubility
but
nicer
to
make
as
an
organic
chemist,
yeah
great
and
just
so
remind
me.
I
should
know
this.
We
you
know,
that's
the
non,
that's
the
des
amino.
You
know
nitrogen
version,
the
benzene
equivalent
rather
than
the
pyridine.
If
we
got
the
we've
been
making
the
two
pyridine
the
whole
time
was
the
three
and
four
pyridine
in
the
original
sar.
I
think
it
was.
A
Okay,
that's
great,
I
think
that
that's
pretty
much
self-contained.
A
A
That's
very
nice,
though,
what's
the
so
I
mean
the
short
at
the
moment
as
things
stand,
if
we
were
offered
some,
you
know
mercer
screening
tomorrow,
how
many
compounds
could
we
send
over.
E
A
Great
okay,
just
in
terms
of
load,
that's
great.
Okay,
all
right
the
combat
numbering
is
complete.
So
that's
all
done!
Oh
yeah!
There
was
something
there's
a
sneaking
action
on
you
here
there.
You
know
just
stuck
it
in
here.
B
B
Yes,
it's
on
the
submissions
section
down
at
the
bottom,
great,
okay,.
A
This
question
about
so
proponent
by
transformation,
so
we're
allowed
to
send
a
couple
of
compounds
over
to
scott
and
also
he's
introduced
me
to
a
company
called
haifa,
which
has
been
done.
So
I'm
setting
up
a
call
with
haifa
to
talk
about
whether
there's
things
we
can
do
together,
which
is
good,
so
that's
done,
but
the
the
question
about
sending
compounds
to
scott.
So
I
guess
what
we
want
to
do
here
is
potentially
send
a.
A
You
know:
an
active
and
an
inactive
to
scott
to
see
if
we
can
do
some
discovery
of
metabolites.
That
might
be
active
right.
So
we
must
be
nearly
ready
to
do
that.
I
guess
what
what
do
you
think
we
need
to
do
to
just
to
finally
send
some
comments
to
scott,
maybe
for
him
to
have
a
look.
C
I
think
that's
frozen
again.
Yeah.
A
B
So
I
have
about
a
hundred
megs
of
the
osa
822,
the
thiathine,
but
that's
one
with
the
weird
peak
in
the
nmr.
So
once
we
resolve
that
we
can
send
it
and
then
inactive
I
don't
maybe
unc
would
have
a
stock
of
some
inactive
ones,
but
I
don't
think
we've
made
any
inactive.
D
B
A
Okay,
we
are.
We
are
parking,
the
whole
issue
about
whether
some
in
vitro
assessment
of
metabolics
liability
so
that's
completed.
I
mean
we
don't
really
have
anything
and
we
need
to
wait
until
we've
got
the
data
anyway.
But
let's
not
worry
too
much
about
that
for
the
moment.
It's
worth
thinking
about
it
or
something
easy,
but
I
don't
think
we
need
to
worry
too
much
about
it
and
then
the
similarity
landscape
thing
so
yeah.
A
I
had
a
very
good
conversation
with
gsk
guy
david
callahan,
james
callahan,
I'm
sorry
just
before
I
went
on
vacation
and
it
was
very
useful
conversation
and
he's
come
back
to
me
with
another
email
and
what
I'm
doing
is
I'm
just
forwarding
him
a
paragraph
that
is
describing
what
we
talked
about
to
check
that
I'm
allowed
to
talk
about
it,
because
the
the
series
that
they
were
looking
at
did
go
off
in
a
different
direction,
and
I
need
to
be
able
to
clear
what
I'm
allowed
to
say.
A
That's
all
because,
because
I
didn't
you
know,
the
conversation
was
was
confidential.
So
this
is
on
me
to
just
send
that
and
get
that.
A
A
He
has,
in
the
meantime,
put
me
in
touch
with
other
people
in
gsk,
who,
I
think
are
familiar
with
the
anti-infective
side
of
things
and
so
may
have
access
to
people
who
may
have
compounds
so
that
it's
sort
of
an
ongoing
thing.
But
I
got
some
useful
information
from
from
james
about
the
original
series
and
what
they
did.
A
I
think
I'm
not
sure
there's
going
to
be
a
huge
amount
of
stuff
there
for
us,
because
I
think
that
these
compounds
represent
compounds
that
arose
early
on
in
a
program
before
it
went
in
a
slightly
different
direction
for
a
different
purpose,
and
so
I
think
they
didn't
do
a
huge
amount
of
sort
of
advanced
pk
work
that
might
be
useful
for
us
on
some
of
these
compounds.
But
let
me
make
sure
that
I'm
allowed
to
talk
about
what
was
done
and
I
can
I
can
fill
everybody
in.
A
So
that's
on
me.
Okay,
design
criteria
keep
an
eye
on
log
p.
I
mean
that's
relevant
to
the
final
component,
we're
just
talking
about,
but
you
know
we're
all
familiar
with
it.
Oh
fame,
chris
did
do
that,
so
he
did
in
fact
do
that.
So,
yes,
he
contacted
the
team
they
have
emailed
and.
A
Digest
all
right,
so
there
there
is,
has
been
contact
made
with
another
team
and
we
can
talk
to
them
about
it,
but
I
have
no
chance
to
deal
with
that
email.
Yet,
okay,
target
product
profile,
oh
yeah,
so
the
target
profile
stuff
that
we
talked
about.
We
were
we're,
then
talking
about
the
activity
against
other
bacteria,
and
I
think
you
dana
in
the
previous
issue.
A
You
mentioned
something
about
the
fact
that
we
well,
it
was
something
about
what
we
had
activity
against
but
found
did
we
find
the
the
actual
original
report
from
coad.
B
B
I
think
it's
called
like
their
primary
screen
or
something
yeah
and
that's
basically,
the
all
these
skate
pathogens
except
the
enterobacter
ones,
which
is
the
only
other
gram
positive.
Besides
mrsa,
that
is
an
escape
pathogen,
so
it
was
basically
screened
against
mrsa
and
then
of
several
gram
negatives.
B
B
A
Okay,
let's
figure
it
out,
then
somehow
I
don't
know
how
to
do
that,
but
we
could
use
an
evaluation
against
others.
Then.
A
B
B
A
Okay,
so
we
need
to
think
about
how
to
do
that.
I
don't
know.
A
A
Right,
okay
and
then
I
might
put
in
another
I'll
digest
some
of
these
action
items
from
the
above
and
make
sure
that
they're
in
here,
because
there's
quite
a
few
here
that
are
small,
which
you
don't
need
to
worry
about
right
now.
But
I'll
do
that
after
the
meeting
and
finalize
this
issue.
A
A
I
think
we're
good.
I
think
we're
good
all
right
great.
So
the
the
chemistry
plan,
though,
is
obviously
to
finish
the
molecules
that
you're
looking
at
now
think
about
that
you
know
simple
inactive
and
then
get
them
ready
for
shipping
to
wherever
we
decide
to
ship,
so
both
for
mercer
and
for
tox
and
for
scott
obak's
metabolic
thing.
Right
I
mean
that's
everything
isn't
it
so
I
guess
we
should
aim
to
try
and
be
shipping
something
in
a
week
or
so,
ideally,
hopefully
just
to
get
things
going
on
the
biology
side
right.
A
We
know,
I
think,
that's
about
reasonable
something
like
10
15
compounds
kind
of
thing.
That
would
be
good
all
right,
perfect.
All
right!
Thank
you
guys.
I
think
that
is
where
we
are
finished,
so
I
will
see
you
guys
in
the
lab.
Pretty
soon
see
ya
all
right
see
you
here.